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Pathogenesis of osteomyelitis - UpToDate

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Pathogenesis of osteomyelitisAuthor: Madhuri M Sopirala, MD, MPH Section Editor: Denis Spelman, MBBS, FRACP, FRCPA, MPH Deputy Editor: Elinor LBaron, MD, DTMH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2020. | This topic last updated: Jan 17, 2020.

INTRODUCTION

Osteomyelitis is an infection involving bone.

The pathogenesis and pathology of osteomyelitis will be reviewed here. The clinical manifestations,diagnosis, and treatment of osteomyelitis are discussed separately. (See "Osteomyelitis in adults: Clinicalmanifestations and diagnosis" and "Approach to imaging modalities in the setting of suspectednonvertebral osteomyelitis" and "Osteomyelitis associated with open fractures in adults" and "Clinicalmanifestations, diagnosis, and management of diabetic infections of the lower extremities" and "Vertebralosteomyelitis and discitis in adults".)

CLASSIFICATION

Osteomyelitis may be divided into two major categories based upon the pathogenesis of infection: (1)hematogenous osteomyelitis and (2) nonhematogenous osteomyelitis, which develops adjacent to acontiguous focus of infection or via direct inoculation of infection into the bone [1-3]. (See "Osteomyelitisin adults: Clinical manifestations and diagnosis", section on 'Classification'.)

Either hematogenous or contiguous-focus osteomyelitis can be classified as acute or chronic. Acuteosteomyelitis evolves over several days to weeks and can progress to a chronic infection [1]. Thehallmark of chronic osteomyelitis is the presence of dead bone (sequestrum). Other common features ofchronic osteomyelitis include involucrum (reactive bony encasement of the sequestrum), local bone loss,and, if there is extension through cortical bone, sinus tracts.

Brodie abscess is a form of subacute osteomyelitis that is usually hematogenous in origin but can occuras a the result of trauma; the classic presentation of Brodie abscess consists of a cavity filled withsuppurative and/or granulation in a long bone metaphysis, surrounded by dense fibrous tissue andsclerotic bone [4].

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PATHOGENESIS

Normal bone is highly resistant to infection. Osteomyelitis develops when there is a large inoculation oforganisms, presence of bone damage, and/or presence of hardware or other foreign material.

The pathogenesis of osteomyelitis is multifactorial and poorly understood; important factors include thevirulence of the infecting organism(s), the host immune status, and the bone vascularity.

Bacteria have a number of virulence determinants that may contribute to development of osteomyelitis inthe appropriate clinical setting. Staphylococcus aureus, the most common cause of osteomyelitis, hasbeen used extensively as a model to study pathogenesis and is therefore discussed in detail in thissection. It is an important cause (though not the only cause) of hematogenous and contiguous focusosteomyelitis. S. aureus produces several extracellular and cell-associated factors that may contribute tovirulence by promoting bacterial adherence, resistance to host defense mechanisms, and proteolyticactivity.

Bacterial adherence — Adherence appears to play a central role in the early stages of S. aureus-induced osteomyelitis or arthritis. S. aureus adheres to a number of components of bone matrix includingfibrinogen, fibronectin, laminin, collagen, bone sialoglycoprotein, and clumping factor A [5-9]. Adherenceis mediated by expression of specific adhesins, called microbial surface components recognizingadhesive matrix molecules [5,10].

The potential importance of adhesins was illustrated in a study in which mice were inoculated withpositive and negative mutants for the collagen adhesin gene: septic arthritis occurred with greaterfrequency in the mutant-positive compared with mutant-negative strains (>70 versus 27 percent) [11].The adhesin-positive strains were also associated with the production of high levels of immunoglobulin G(IgG) and interleukin 6. In other experimental studies, S. aureus adhesion was blocked by antibodiesdirected against the collagen receptor [12]. It has been speculated that bone and other invasive S.aureus infections might be prevented by an adhesin-derived vaccine [13].

Collagen-binding adhesin (CNA) of S. aureus is a virulence factor for arthritis in several animal models[14,15]. The expression of CNA permits the attachment of pathogen to cartilage [16]. How CNAcontributes to virulence and whether it is important in humans are unclear.

Fibronectin-binding protein rapidly coats implanted foreign bodies in vivo and adheres to biomaterialscoated with host proteins. It may be particularly important in infections associated with prosthetic joints[7]. Atomic-force microscopy has demonstrated that fibronectin-binding proteins A and B (FnBPA andFnBPB) form bonds with host fibronectin and may play a key role in binding S. aureus to implants [17].(See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Resistance to host defense — The ability of microorganisms to resist host defense mechanisms at thecellular and matrix levels presents difficulties in the management of osteomyelitis.


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As an example, S. aureus can survive intracellularly in cultured osteoblasts. Persistence of intracellularpathogens within osteoblasts may also be an important factor in the pathogenesis of osteomyelitis. Whendigested by osteoblasts, S. aureus undergoes phenotypic alteration, which renders it more resistant tothe action of antimicrobials. This may explain in part the high relapse rate of osteomyelitis treated withantimicrobials for a short duration [2,18]. Osteoblast persistence of S. aureus in chronic osteomyelitis hasbeen described [19,20].

Arachidonic acid metabolites, such as prostaglandin E2, a strong osteoclast agonist, decrease thebacterial inoculum needed to produce infection.

S. aureus expresses a 42-kDa protein, protein A, which is bound covalently to the outer peptidoglycanlayer of their cell walls. Protein A binds to the Fc portion of IgG on polymorphonuclear leukocytes,interfering with opsonization and phagocytosis of S. aureus [21]. Loss of protein A activity reducesvirulence [22].

S. aureus secretes two toxins, exotoxin and toxic shock syndrome toxin (TSST-) 1, which exert importanteffects on the immune system when administered parenterally. The toxins act as superantigens andsuppress plasma cell differentiation; they also stimulate production of cytokines, such as interleukin 1[23], interferon-gamma, and tumor necrosis factor-alpha [24]. Animals infected with strains of S. aureusisogenic for TSST-1 develop frequent and severe arthritis [25]. Staphylococcal enterotoxin and TSST-1subvert the cellular and humoral immune system, which may determine whether a local infection iseliminated or develops into osteomyelitis or septic arthritis.

HISTOPATHOLOGY

Overview — Acute osteomyelitis demonstrates suppurative infection with acute inflammatory cells,accompanied by edema, vascular congestion, and small vessel thrombosis (picture 1 and picture 2). Inearly acute disease, the vascular supply to the bone is compromised by infection extending into thesurrounding soft tissue. When both the medullary and periosteal blood supplies are compromised, largeareas of dead bone (sequestra) may form [26]. Within this necrotic and ischemic tissue, bacteria can bedifficult to eradicate even in the setting of an intense host response, surgery, and antibiotic therapy.

Clinically and histologically, acute osteomyelitis blends into chronic osteomyelitis. Pathologic features ofchronic osteomyelitis include necrotic bone, the formation of new bone, and polymorphonuclearleukocyte exudation joined by large numbers of lymphocytes, histiocytes, and occasional plasma cells(picture 3).

Necrosis of normal tissue is an important feature of osteomyelitis. Dead bone is absorbed by the action ofgranulation tissue developing at its surface. Absorption takes place earliest and most rapidly at thejunction of living and necrotic bone. If the area of the dead bone is small, it is entirely destroyed bygranulation tissue, leaving a cavity behind. The necrotic cancellous (trabecular) bone in localized








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osteomyelitis, even though extensive, is usually absorbed. Some of the dead cortical bone is graduallydetached from living bone to form a sequestrum [3,27].

Host defense and mesenchymal cells, mainly the polymorphonuclear leukocytes, macrophages, and theosteoclasts, elaborate proteolytic enzymes that break down organic elements in the dead bone (picture2). Because of lost blood supply, dead bone appears whiter than living bone. Cancellous bone isabsorbed rapidly and may be completely sequestrated or destroyed in two to three weeks, but necroticcortex may require two weeks to six months for separation. After complete separation, the dead bone isslowly eroded by granulation tissue and absorbed.

New bone formation is another characteristic feature of osteomyelitis. New bone forms from the survivingfragments of periosteum, endosteum, and the cortex in the region of the infection and is produced by avascular reaction to the infection. New bone may be formed along the intact periosteal and endostealsurfaces and may also arise when the periosteum forms an encasing sheath of live bone (involucrum)surrounding the dead bone. Involucrum is irregular and is often perforated by openings through whichpus may track into the surrounding soft tissues and eventually to the skin surfaces through a sinus tract.The involucrum can gradually increase in density and thickness to form part or all of a new shaft.

New bone increases in amount and density for weeks or months, according to the size of the bone andthe extent and duration of infection. Endosteal new bone may proliferate and obstruct the medullarycanal. After host defense removal or surgical removal of the sequestrum, the body, especially in children,may fill the remaining cavity with new bone. However, in adults, the cavity may persist or the space maybe filled with fibrous tissue that may connect with the skin surface via a sinus tract.

The surviving bone in the osteomyelitis field usually becomes osteoporotic during the active period ofinfection. Osteoporosis is the result of the inflammatory reaction and atrophy disuse. After the infectionsubsides, bone density increases partially from reuse (eg, of a limb); the bone may undergo extensivetransformation to conform to areas of new mechanical stresses. It may be difficult to distinguish betweenthe old living bone and the newly formed bone as time passes. All traces of osteomyelitis can disappearin children and, to a lesser extent, in adults.

Differences by age — There are basic differences in the pathology of osteomyelitis in infants, children,and adults.

In neonates, small capillaries cross the epiphyseal growth plate and permit extension of infection into theepiphysis and joint space. The cortical bone of the neonate and infant is thin and loose, consistingpredominantly of woven bone, which permits escape of the pressure caused by infection, but promotesrapid spread of the infection directly into the subperiosteal region. A large sequestrum is not producedbecause extensive infarction of the cortex does not occur; however, a large subperiosteal abscess canform [28,29].

In children older than one year, infection presumably starts in the metaphyseal sinusoidal veins and iscontained by the growth plate. Dye injection experiments described in the 1920s have depicted







metaphyseal vessels as a series of capillary loops terminating adjacent to the growth plate andexpanding into dilated venous sinusoids resulting in sluggish blood flow, thus predisposing to bacterialdeposition [30]. Subsequently, electron micrographic studies have described rapidly growing vessels witha single layer of discontinuous endothelium at their tips, through which bacteria may pass during anepisode of bacteremia, thus initiating osteomyelitis [31,32]. An experimental avian model confirmed thatbacteria are deposited initially at the end of metaphyseal tunnels that provide a framework for the rapidlygrowing metaphyseal vessels. The presence of endothelial gaps in the tips of metaphyseal vessels,regardless of blood flow rates, may play a critical role in the initiation of osteomyelitis [33]. The joint isspared unless the metaphysis is intracapsular. The infection spreads laterally where it breaks through thecortex and lifts the loose periosteum to form a subperiosteal abscess [29,34].

In adults, the growth plate has resorbed, and the infection may again extend to the joint spaces as ininfants. In addition, the periosteum is firmly attached to the underlying bone; as a result, subperiostealabscess formation and intense periosteal proliferation are less frequently seen. The infection can erodethrough the periosteum, forming a draining sinus tract(s) [35].

CLINICAL FORMS

Issues related to clinical manifestations and diagnosis of osteomyelitis are discussed separately. (See"Osteomyelitis in adults: Clinical manifestations and diagnosis".)

Hematogenous osteomyelitis — Hematogenous osteomyelitis is the most common form ofosteomyelitis in infants and children [1]. The pathogenesis is discussed separately. (See "Hematogenousosteomyelitis in children: Epidemiology, pathogenesis, and microbiology".)

In adults, vertebral osteomyelitis is the most common form of hematogenous osteomyelitis; thepathogenesis is discussed separately. (See "Vertebral osteomyelitis and discitis in adults", section on'Pathogenesis'.)

Other sites of hematogenous osteomyelitis in adults include the long bones, pelvis, and clavicle. (See"Osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Hematogenousosteomyelitis'.)

In people who inject drugs (PWID), osteomyelitis assumes an axial distribution involving vertebralcolumn, especially the lumbar spine; the reason for the axial distribution in this patient population isuncertain. Osteomyelitis can also occur in the sternum, extremities and sacroiliac joints. Commonmicrobiologic causes include S. aureus, Pseudomonas spp, and Candida spp. In addition, osteomyelitisdue to oral flora can occur osteomyelitis among PWID who lick the needle tip or skin before infection [36].

Tuberculous osteomyelitis usually occurs from reactivation of tuberculous bacilli lodged in bone duringthe mycobacteremia occurring at the time of the primary infection. (See "Skeletal tuberculosis", sectionon 'Spondylitis (Pott disease)'.)








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Nonhematogenous osteomyelitis — Nonhematogenous osteomyelitis, which develops adjacent to acontiguous focus of infection or via direct inoculation of infection into the bone (via trauma, surgery orhardware placement). The clinical manifestations and diagnosis of nonhematogenous osteomyelitis arediscussed separately. (See "Osteomyelitis in adults: Clinical manifestations and diagnosis", section on'Nonhematogenous osteomyelitis'.)

Skull base osteomyelitis can occur as a complication of otogenic, sinogenic, odontogenic, or rhinogenicinfections [37]. The pathogenesis is not fully understood; it may include a combination of factors includinghypoperfusion and diminished immune response. In addition, use of water irrigation for cerumendisimpaction may reduce the cerumen lysozyme content, leading to alkaline pH and increasedsusceptibility to Pseudomonas infection [38]. Malignant otitis externa can spread from the externalauditory canal to the skull base [39,40]. Potential complications include involvement cranial nerves, theparotid gland, the temporomandibular joint, the carotid artery, and the jugular vein.

Osteomyelitis involving the hand can occur as a result of animal or human bite. Pathogens includeaerobic and anaerobic bacteria; streptococcal and staphylococcal species are most commonly reported[41-43]. (See "Animal bites (dogs, cats, and other animals): Evaluation and management" and "Humanbites: Evaluation and management".)

Contiguous osteomyelitis associated with vascular insufficiency occurs most commonly in the setting ofdiabetes mellitus and/or peripheral vascular disease. Inadequate tissue perfusion and predisposes todevelopment of osteomyelitis following minor foot trauma [35].

SUMMARY

The hallmark of chronic osteomyelitis is the presence of dead bone (sequestrum). Other commonfeatures of chronic osteomyelitis include involucrum (reactive bony encasement of the sequestrum),local bone loss, and, if there is extension through cortical bone, sinus tracts. (See 'Introduction'above.)

●

The pathogenesis of osteomyelitis is multifactorial and poorly understood. Some important factorsinclude virulence of the infecting organism(s), underlying immune status of the host, and the type,location, and vascularity of the bone. (See 'Pathogenesis' above.)

●

Staphylococcus aureus can survive intracellularly in cultured osteoblasts. Persistence of intracellularpathogens within osteoblasts may also be an important factor in the pathogenesis of osteomyelitis.When digested by osteoblasts, S. aureus undergoes phenotypic alteration, which renders it moreresistant to the action of antimicrobials. This may explain in part the high relapse rate ofosteomyelitis treated with antimicrobials for a short duration. (See 'Resistance to host defense'above.)

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Acute osteomyelitis demonstrates suppurative infection with acute inflammatory cells, accompanied●

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ACKNOWLEDGMENT

The editors of UpToDate would like to acknowledge LiYan Yin, MD, and Jason Calhoun, MD, whocontributed to earlier versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Lew DP, Waldvogel FA. Osteomyelitis. Lancet 2004; 364:369.

2. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med 1997; 336:999.

3. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeuticconsiderations and unusual aspects. N Engl J Med 1970; 282:198.

4. Roberts JM, Drummond DS, Breed AL, Chesney J. Subacute hematogenous osteomyelitis inchildren: a retrospective study. J Pediatr Orthop 1982; 2:249.

5. Foster TJ, Höök M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 1998;6:484.

6. Herrmann M, Vaudaux PE, Pittet D, et al. Fibronectin, fibrinogen, and laminin act as mediators ofadherence of clinical staphylococcal isolates to foreign material. J Infect Dis 1988; 158:693.

7. Johansson A, Flock JI, Svensson O. Collagen and fibronectin binding in experimentalstaphylococcal osteomyelitis. Clin Orthop Relat Res 2001; :241.

8. Yacoub A, Lindahl P, Rubin K, et al. Purification of a bone sialoprotein-binding protein from

by edema, vascular congestion, and small vessel thrombosis (picture 1 and picture 2). Pathologicfeatures of chronic osteomyelitis include necrotic bone, the formation of new bone, andpolymorphonuclear leukocyte exudation joined by large numbers of lymphocytes, histiocytes, andoccasional plasma cells (picture 3). (See 'Histopathology' above.)

New bone formation is another characteristic feature of osteomyelitis. New bone forms from thesurviving fragments of periosteum, endosteum, and the cortex in the region of the infection and isproduced by a vascular reaction to the infection. (See 'Histopathology' above.)

●

The surviving bone in the osteomyelitis field usually becomes osteoporotic during the active period ofinfection. Osteoporosis is the result of the inflammatory reaction and atrophy disuse. (See'Histopathology' above.)

●

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Staphylococcus aureus. Eur J Biochem 1994; 222:919.

9. Rydén C, Tung HS, Nikolaev V, et al. Staphylococcus aureus causing osteomyelitis binds to anonapeptide sequence in bone sialoprotein. Biochem J 1997; 327 ( Pt 3):825.

10. Shirtliff ME, Leid JG, Costerton JW. The Basic Science of Musculoskeletal Infections. In: Musculoskeletal Infections, Calhoun JH, Mader JT (Eds), Marcel Decker, New York 2003.

11. Patti JM, Bremell T, Krajewska-Pietrasik D, et al. The Staphylococcus aureus collagen adhesin is avirulence determinant in experimental septic arthritis. Infect Immun 1994; 62:152.

12. Switalski LM, Patti JM, Butcher W, et al. A collagen receptor on Staphylococcus aureus strainsisolated from patients with septic arthritis mediates adhesion to cartilage. Mol Microbiol 1993; 7:99.

13. Patti JM. A humanized monoclonal antibody targeting Staphylococcus aureus. Vaccine 2004; 22Suppl 1:S39.

14. Xu Y, Rivas JM, Brown EL, et al. Virulence potential of the staphylococcal adhesin CNA inexperimental arthritis is determined by its affinity for collagen. J Infect Dis 2004; 189:2323.

15. Therrien R, Lacasse P, Grondin G, Talbot BG. Lack of protection of mice against Staphylococcusaureus despite a significant immune response to immunization with a DNA vaccine encodingcollagen-binding protein. Vaccine 2007; 25:5053.

16. Patti JM, Boles JO, Höök M. Identification and biochemical characterization of the ligand bindingdomain of the collagen adhesin from Staphylococcus aureus. Biochemistry 1993; 32:11428.

17. Buck AW, Fowler VG Jr, Yongsunthon R, et al. Bonds between fibronectin and fibronectin-bindingproteins on Staphylococcus aureus and Lactococcus lactis. Langmuir 2010; 26:10764.

18. Norden CW. Lessons learned from animal models of osteomyelitis. Rev Infect Dis 1988; 10:103.

19. Webb LX, Wagner W, Carroll D, et al. Osteomyelitis and intraosteoblastic Staphylococcus aureus. JSurg Orthop Adv 2007; 16:73.

20. Ellington JK, Harris M, Hudson MC, et al. Intracellular Staphylococcus aureus and antibioticresistance: implications for treatment of staphylococcal osteomyelitis. J Orthop Res 2006; 24:87.

21. Greenberg DP, Bayer AS, Cheung AL, Ward JI. Protective efficacy of protein A-specific antibodyagainst bacteremic infection due to Staphylococcus aureus in an infant rat model. Infect Immun1989; 57:1113.

22. Gemmell CG, Goutcher SC, Reid R, Sturrock RD. Role of certain virulence factors in a murinemodel of Staphylococcus aureus arthritis. J Med Microbiol 1997; 46:208.

23. Nair S, Song Y, Meghji S, et al. Surface-associated proteins from Staphylococcus aureus
































demonstrate potent bone resorbing activity. J Bone Miner Res 1995; 10:726.

24. Littlewood-Evans AJ, Hattenberger MR, Lüscher C, et al. Local expression of tumor necrosis factoralpha in an experimental model of acute osteomyelitis in rats. Infect Immun 1997; 65:3438.

25. Schlievert PM. Role of superantigens in human disease. J Infect Dis 1993; 167:997.

26. Loughran AJ, Gaddy D, Beenken KE, et al. Impact of sarA and Phenol-Soluble Modulins on thePathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus. Infect Immun2016; 84:2586.

27. Mader JT, Calhoun JH. Osteomyelitis. In: Principles and Practice of Infectious Diseases, Mandell GL, Douglas RG, Bennett Jr JE (Eds), Churchill Livingstone, New York 1995. p.1039.

28. De Boeck H. Osteomyelitis and septic arthritis in children. Acta Orthop Belg 2005; 71:505.

29. Morrissey RT. Bone and Joint Infections. In: Lovell and Winter's Pediatric Ortopaedics, 3rd ed, Morrissey RT (Ed), Lippincott, Philadelphia 1990. p.539.

30. Hobo T. Zur Pathogenesed er akuten haematogenen Osteomyelitism, it BeriicksichtigundgerVitalfarbungslehre. Acta Scholae Medicina Universitas Imperialis Kioto 1921; 4:1.

31. Howlett CR. The fine structure of the proximal growth plate and metaphysis of the avian tibia:endochondral osteogenesis. J Anat 1980; 130:745.

32. Ham KN, Hurley JV, Ryan GB, Storey E. Localization of particulate carbon in metaphyseal vesselsof growing rats. Aust J Exp Biol Med Sci 1965; 43:625.

33. Emslie KR, Nade S. Pathogenesis and treatment of acute hematogenous osteomyelitis: evaluationof current views with reference to an animal model. Rev Infect Dis 1986; 8:841.

34. Jansson A, Jansson V, von Liebe A. [Pediatric osteomyelitis]. Orthopade 2009; 38:283.

35. Calhoun JH, Manring MM. Adult osteomyelitis. Infect Dis Clin North Am 2005; 19:765.

36. Tande AJ, Steckelberg JM, Osmon DR, Berbari EF. Osteomyelitis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th, Bennet JE, Dolin R, Blaser MJ (Eds), Philadelphia 2019. p.1418.

37. Khan MA, Quadri SAQ, Kazmi AS, et al. A Comprehensive Review of Skull Base Osteomyelitis:Diagnostic and Therapeutic Challenges among Various Presentations. Asian J Neurosurg 2018;13:959.

38. Driscoll PV, Ramachandrula A, Drezner DA, et al. Characteristics of cerumen in diabetic patients: akey to understanding malignant external otitis? Otolaryngol Head Neck Surg 1993; 109:676.


























39. Alva B, Prasad KC, Prasad SC, Pallavi S. Temporal bone osteomyelitis and temporoparietalabscess secondary to malignant otitis externa. J Laryngol Otol 2009; 123:1288.

40. Carfrae MJ, Kesser BW. Malignant otitis externa. Otolaryngol Clin North Am 2008; 41:537.

41. Peeples E, Boswick JA Jr, Scott FA. Wounds of the hand contaminated by human or animal saliva.J Trauma 1980; 20:383.

42. Shields C, Patzakis MJ, Meyers MH, Harvey JP Jr. Hand infections secondary to human bites. JTrauma 1975; 15:235.

43. Resnick D, Pineda CJ, Weisman MH, Kerr R. Osteomyelitis and septic arthritis of the handfollowing human bites. Skeletal Radiol 1985; 14:263.

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GRAPHICS

Acute osteomyelitis

Light micrograph of acute osteomyelitis of the tibia shows manydisconnected bony trabeculae in a sea of inflammatory cells (red arrow) anda single multinucleated giant cell (black arrow). The surfaces of thetrabeculae (white arrows) have a few undifferentiated, spindle-shapedconnective tissue elements. There is little evidence of active bone formationor bone resorption.

Courtesy of Jon Mader, MD.

Graphic 72714 Version 3.0



Early repair in acute osteomyelitis

Light micrograph in acute osteomyelitis of the tibial articular apparatus. Thepresence of whorls of chondrocytes (arrows) indicates early tissue repair inwhich multinucleated osteoclasts (dashed arrows) are actively remodelingthe subchondral region. Bone (arrowhead) has replaced the mature lamellarstructure, and the medullary spaces are largely filled with inflammatory cellsand fibrin.



Contributor Disclosures

Madhuri M Sopirala, MD, MPH Nothing to disclose Denis Spelman, MBBS, FRACP, FRCPA, MPH Nothing todisclose Elinor L Baron, MD, DTMH Nothing to disclose

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Chronic osteomyelitis

Light micrograph of chronic osteomyelitis of the tibia. Against a backgroundof inflammatory cells (arrow), there are thickened bony trabeculae(arrowhead) lined by plump osteoblasts, which are actively forming bone.The accumulation of small dark cells (lymphocytes; dashed arrows)represent sites of perivascular inflammation.






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Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis - UpToDate



Approach to imaging modalities in the setting of suspectednonvertebral osteomyelitisAuthor: Charles E Spritzer, MD Section Editor: Denis Spelman, MBBS, FRACP, FRCPA, MPH Deputy Editor: Elinor L Baron,MD, DTMH


Literature review current through: Feb 2020. | This topic last updated: Feb 28, 2020.

INTRODUCTION

Radiographic imaging is useful for confirming or excluding the diagnosis of osteomyelitis, delineating theextent of disease, and planning therapy (table 1). Imaging findings must be interpreted in clinical context[1]. Osteomyelitis may occur in any bone; the largest body of data on imaging modalities for evaluation ofosteomyelitis comes from the literature on diabetic foot infections.

The benefits and limitations of plain radiographs, magnetic resonance imaging, computed tomography,nuclear modalities, and ultrasonography for the diagnosis of osteomyelitis will be reviewed here. Anintegrated diagnostic approach to evaluation of adults with suspected osteomyelitis is presented in detailseparately. (See "Osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Clinicalapproach'.)

Issues related to radiographic imaging in the setting of suspected vertebral osteomyelitis and discitis arediscussed separately. (See "Vertebral osteomyelitis and discitis in adults".)

PATHOPHYSIOLOGY OF OSTEOMYELITIS

Osteomyelitis can occur as a result of hematogenous seeding, contiguous spread of infection to bonefrom adjacent soft tissues and joints, or direct inoculation of infection into the bone as a result of traumaor surgery. The most commonly affected adults are individuals with poorly controlled diabetes, peripheralneuropathy, and vascular insufficiency who develop ulcers and subsequent osteomyelitis in one or morebones of the foot [2,3]. (See "Osteomyelitis in adults: Clinical manifestations and diagnosis", section on'Classification'.)

In the setting of osteomyelitis, inflammatory exudate in the marrow causes elevated medullary pressure,which compresses vascular channels, leading to ischemia and bone necrosis. If the areas of necrotic

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bone separate from the remaining viable bone, sequestra are formed. Surviving bone and periosteumultimately produce a sheath of bone surrounding the area of necrosis, which is referred to as aninvolucrum. Both the sequestra and involucrum may be apparent radiographically (image 1 and image 2)[2,3].

Acute osteomyelitis refers to infection in the bone prior to development of sequestra, usually measured indays or weeks. In some forms of osteomyelitis, development of sequestra is relatively slow (such asvertebral osteomyelitis), while in others the development of sequestra occurs relatively rapidly (such asosteomyelitis in the setting of prosthetic devices or compound fractures) [1].

Following formation of sequestra, the infection is considered to be chronic osteomyelitis. Other hallmarksof chronic osteomyelitis include involucrum, local bone loss, and sinus tracts (extension of infectionthrough cortical bone) (image 1 and image 2). Occasionally, pus may exist in an opening (cloaca) ofinvolucrum.

SELECTING AN IMAGING MODALITY

The evaluation of suspected osteomyelitis includes radiographic imaging interpreted together with theclinical history, culture data, and laboratory results. The optimal imaging modality depends upon thespecific clinical circumstances and should be tailored accordingly. An integrated diagnostic approach forosteomyelitis is outlined in detail separately. (See "Osteomyelitis in adults: Clinical manifestations anddiagnosis", section on 'Clinical approach'.)

In general, if osteomyelitis is suspected based on clinical history and physical findings, imaging shouldbegin with conventional radiographs (plain x-rays) of the involved area. A more sophisticated imagingmodality should be pursued for patients with normal radiographs or radiographs suggestive ofosteomyelitis without definitive characteristic features; such imaging may be used to establish adiagnosis of osteomyelitis and/or to define the extent of disease for surgical planning. In general,magnetic resonance imaging (MRI) is the imaging modality with greatest sensitivity for diagnosis ofosteomyelitis; if MRI is contraindicated, a labeled leukocyte scan, sulfur colloid marrow scan, computedtomography (CT), or positron emission tomography/CT is appropriate [4-6]. MRI, CT, andultrasonography may all be useful in assessing the associated soft tissue abnormalities.

IMAGING MODALITIES

The sensitivity of conventional radiographs for detection of acute osteomyelitis is limited, and thespecificity of some imaging modalities may be limited by confounding bony pathology. Negativepredictive values are high for magnetic resonance imaging (MRI) and radionuclide studies.

Conventional radiography — Conventional radiography (eg, plain x-ray) is a reasonable initial imagingmodality for evaluation of suspected osteomyelitis in patients with at least two weeks of clinical









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symptoms; it is not adequate for detection of early osteomyelitis [7]. Conventional radiographs are usefulfor identification of noninfectious pathology and for identifying air within soft tissues (image 3). Thesensitivity of conventional radiographs range from 22 to 75 percent [8]. One meta-analysis includingdiabetic foot ulcers reported a pooled sensitivity and specificity of 0.54 and 0.68, respectively [9].

Radiographic findings of osteomyelitis include soft tissue swelling, osteopenia, cortical loss, bonydestruction, and periosteal reaction [10-13]. Radiographs may be unremarkable for the first 10 to 14 daysfollowing infection [3]. Bony destructive changes on radiography lag at least two weeks behind clinicalinfection; approximately 50 to 75 percent of the bone matrix must be destroyed before plain radiographsdemonstrate lytic changes [14].

Following trauma, radiographic findings of architectural distortion, osteopenia due to disuse, and normalfracture healing may be difficult to distinguish from osteomyelitis [15]. In addition, conventionalradiography may be insufficient to distinguish osteomyelitis from other processes such as Charcotarthropathy and fracture [16].In the presence of orthopedic hardware, findings of osteomyelitis mayinclude fracture, nonunion, or periprosthetic lucency. In the setting of chronic osteomyelitis, reactivesclerosis, sequestra, and involucrum may be observed [10,11].

Magnetic resonance imaging — Magnetic resonance imaging (MRI) has excellent sensitivity fordiagnosis of osteomyelitis. After conventional radiographic evaluation, MRI is generally considered thestudy of choice for further assessment [4,5,17-20]. It is useful for obtaining images delineating the extentof cortical destruction characteristic of osteomyelitis, as well as to evaluate for presence of bone marrowabnormality, soft tissue inflammation (such as in the setting of cellulitis, myositis, and/or ulceration), andischemia (picture 1) [21,22]. MRI may demonstrate abnormal marrow edema as early as one to five daysfollowing onset of infection [9,17,23]. Intravenous contrast does not improve the detection ofosteomyelitis on MRI but does improve the distinction between phlegmon, necrotic tissue, and abscess.

MRI has high sensitivity and negative predictive value [1,4,9,24-26]. In one meta-analysis, the sensitivityof MRI was superior to conventional radiography and nuclear modalities (including bone scans and whiteblood cell studies) [24]. Another meta-analysis including patients with diabetic foot ulceration whounderwent MRI reported a pooled sensitivity and specificity of 90 and 79 percent, respectively (image 4)[9]. A subsequent meta-analysis confirmed the high sensitivity of 93 percent but with a poorer specificityof 70 percent; technetium-99m hexamethylpropylene amine oxime (HMPAO)-tagged white blood cellsand fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) had higherspecificities [6]. Given the high negative predictive value of MRI, an MRI with no evidence ofosteomyelitis is sufficient for exclusion of osteomyelitis if clinical signs or symptoms have been presentfor at least one week [1].

Both T1-weighted and fat-suppressed T2-weighted (or short tau inversion recovery) images should beobtained; these are usually performed in the same imaging plane, and multiple imaging planes areusually obtained. Abnormal osseous signal on all sequences in the region of concern in the correctclinical setting confirms the diagnosis of osteomyelitis. Soft tissue abnormalities adjacent to the bone and











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bony destruction increase diagnostic confidence [24]. Absence of osseous signal abnormality on allsequences excludes infection.

MRI may overestimate the extent and duration of infection, given its high sensitivity. Reactive marrowedema seen on fluid sensitive images may coexist with true marrow infection, leading to an imagingabnormality that is larger than the area of actual infection. However, the T1-weighted images likelyunderestimate the extent of disease. One study suggests that marked ischemia may affect the overallaccuracy of MRI in detecting osteomyelitis [27]. Lastly, bone marrow changes may persist for weeks tomonths after osteomyelitis begins to respond to therapy.

Bone marrow signal abnormality on MRI is a nonspecific finding that can be seen with a variety of otherpathologies including contusion, fracture, postsurgical change, arthritis, neoplasm, and Charcotarthropathy [28]. Establishing the correct diagnosis depends on the clinical setting and on additionalimaging findings. Moreover, if infection coexists with additional pathology that can cause bone marrowedema, MRI cannot reliably distinguish between marrow changes attributable to infection and thoseattributable to other pathology.

It may be diagnostically challenging to distinguish a diabetic foot with Charcot arthropathy fromconcomitant infection on MRI. The presence of sinus tracts, fluid collections with thick rim or diffuseenhancement, and extensive adjacent marrow abnormality are concerning for Charcot withsuperimposed osteomyelitis [29]. In cases of severe Charcot arthropathy, definitive radiographicexclusion of osteomyelitis may not be possible. Preliminary data suggest that techniques such asdiffusion weighted MRI may help in the differentiation of Charcot arthropathy from osteomyelitis [30].

MRI is the imaging modality of choice for delineating the anatomy of the spinal cord and adjacentosseous and soft tissues. (See "Vertebral osteomyelitis and discitis in adults".)

Gadolinium contrast-enhanced images are not required to diagnose acute osteomyelitis. However, theadministration of contrast is useful to enhance visualization of sinus tracts, fistulas, and necrotic tissueand to distinguish between abscess and phlegmon (picture 1) [21,22]. The utility of gadolinium contrast-enhanced images is increased in chronic osteomyelitis as areas of active inflammation will enhance andabscesses are well demarcated [17].

The penumbra sign, a thin layer of granulation tissue lining a bone abscess cavity, may be seen inosteomyelitis (image 5). This finding produces a higher signal on T1-weighted magnetic resonanceimages; in one study, it had a sensitivity and specificity of 73 and 99 percent, respectively [31].

Metallic hardware can give rise to artifact that may degrade MRI image quality and limit diagnosticcapability.

Computed tomography — Computed tomography (CT) is more sensitive than conventional radiographyfor assessing cortical and trabecular integrity, periosteal reaction, intraosseous gas, soft tissue gas, andthe extent of sinus tracts (image 6) [12,15,17,32-35]. It is useful in chronic osteomyelitis and may be themost useful modality to evaluate for the presence of osseous sequestra and involucrum [1,20].













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Intravenous contrast is required for detection of soft tissue abnormalities such as sinus tracts.Noncontrast CT allows assessment of gas but does not evaluate soft tissue pathology as well as acontrasted CT.

Metallic hardware can give rise to artifact that may degrade CT image quality and limit diagnosticcapability (image 7).

Nuclear modalities — A nuclear study may be useful if metal hardware precludes MRI or CT. Nuclearimaging has high sensitivity for detecting evidence of inflammation and therefore tends to be morereliable for evaluation of acute infection than chronic infection. There are a number of different nuclearstudy modalities, including positron emission tomography (PET) scans, three-phase bone scans, andtagged white blood cell (WBC) scans; gallium scans are used less often.

A major limitation of nuclear studies is that radiographic evidence of bone turnover or inflammation due tononinfectious bone pathology may be confused with osteomyelitis [36-39]. Such conditions include recenttrauma or surgery, recently healed osteomyelitis, septic arthritis, degenerative joint disease, bone tumors,and Paget disease [40,41]. False-negative results are possible in areas of relative ischemia (a commoncomorbidity in osteomyelitis) since radiotracer may not be adequately delivered to the target site.

Flourine-18-labeled fluorodeoxyglucose (FDG) imaging using PET is a relatively new modality that hasshown promising results for imaging of infection [4,42-45] and may overcome some of the limitations withother nuclear imaging studies.

Positron emission tomography – 18F-FDG PET uses 18F-FDG, a glucose analog that accumulatesin leukocytes, which in turn accumulate at the site of infection. The 18F-FDG molecule accumulatesrapidly even in poorly perfused areas due to its small size [46]. As such, imaging is performed 30 to60 minutes after tracer injection, making the study faster than other nuclear medicine studies [17].The tracer provides high-resolution tomographic images and, when combined with CT (18F-FDGPET CT), provides the anatomic detail of conventional CT scans.

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Data suggest that 18F-FDG PET is useful for assessing both acute and chronic osteomyelitis[26,46]. A meta-analysis including 299 patients from nine studies reported a pooled sensitivity andspecificity of 74 and 91 percent, respectively [26]. A subsequent meta-analysis including more than250 patients reported a sensitivity and specificity 89 and 92 percent, respectively [6]. A meta-analysis evaluating imaging modalities in patients with chronic osteomyelitis reported PET to besuperior to other modalities (sensitivity and specificity of 96 and 91 percent, respectively) [47].Preliminary data suggest 18F-FDG PET may be useful in distinguishing Charcot arthropathy fromnormal joints and patients with osteomyelitis [48]. 18F-FDG PET is useful in assessing peripheralpost-traumatic osteomyelitis [49].

18F-FDG PET may be useful for diagnosing spondylodiscitis. (See "Vertebral osteomyelitis anddiscitis in adults".)




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18F-FDG PET has several disadvantages; these include the inability to discriminate tumor frominfection, high cost, false positives due to postsurgical inflammatory changes, and limited availability.Tissue inflammation associated with spinal hardware and spinal degenerative changes may beconfounders [46]. As such, 18F-FDG PET may be useful as an alternative to MRI for circumstancesin which MRI is contraindicated or as a supplement when MRI is equivocal.

Three-phase bone scan – Three-phase bone scans use a radionuclide tracer that accumulates inareas of bone turnover and increased osteoblast activity (such as technetium-99m bound to aphosphorus-containing compound) [40]. The scans are performed using a gamma camera at threepoints following tracer injection: immediately after injection (blood flow phase), 15 minutes afterinjection (blood pool phase), and four hours after injection (osseous phase). In the setting ofosteomyelitis, there is intense uptake in all three phases; in the setting of cellulitis, there is increasedactivity only in the first two phases and normal or mild diffuse increased activity in the third phase[12].

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The sensitivity and specificity of three-phase bone scan for detection of osteomyelitis variesdepending on the appearance of correlative radiographs. If conventional radiographs are normal,three-phase bone scan has a sensitivity and specificity of about 95 percent [1,40,50]. If radiographsdemonstrate noninfectious disorders such as fracture or Charcot arthropathy, (entities associatedwith bone formation and radionuclide tracer uptake), false-positive results are more likely. False-negative results are possible in early osteomyelitis or in the setting of chronic osteomyelitis withimpaired blood flow or infarction [41]. In one meta-analysis, the pooled sensitivity and specificity forthree-phase bone scans were 0.81 and 0.28, respectively [9].

Tagged white blood cell scan – A tagged WBC scan uses autologous WBCs and requires acirculating WBC of at least 2000 per microliter [19]. The WBCs are labeled with indium 111oxyquinoline, gallium-67, or technetium-99m [1]. To perform the study, blood is drawn from thepatient, and the white blood cells are separated for labeling with tracer; after a few hours, the taggedwhite cells are returned to the patient's circulation via intravenous injection. The time of imaging isdependent upon the isotope used. For technetium-99m, imaging begins four to six hours afteradministration and may be repeated at 18 and 30 hours. For indium-111, images are acquired 18 to30 hours following injection [17]. Images are taken up to 24 hours later. The tagged white cellsaccumulate in the bone marrow and at sites of inflammation or infection; they are not specific forbone. The different tagging agents result in different advantages and disadvantages for the agentused. For example, indium 111-labeled WBCs are more stable than those tagged with technetium99m, but the scans are of much lower resolution [46].

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Tagged WBC scans have similar sensitivity to bone scans for evaluation of osteomyelitis [51].Reported sensitivities and specificities range from 72 to 100 percent and 67 to 100 percent,respectively [46]. In a meta-analysis comprising 206 patients undergoing indium-111 WBCscintigraphy, a 92 percent sensitivity and 75 percent specificity were reported. In the same meta-analysis, using technetium-99m HMPAO in 406 patients, the specificity improved to 92 percent with




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Ultrasonography — Ultrasound may be a useful diagnostic tool for circumstances in which othermodalities are not readily available. Typically, bone is not well depicted by ultrasound, because the

a sensitivity of 91 percent [6]. Despite these results, it has been reported that specificity can be poorif corresponding radiographs are not normal [51]. In addition, regions with substantial quantities ofred marrow (such as the vertebral bodies) are not visualized reliably with this modality; WBC scansmay best be used in the distal extremities [41]. Although studies suggest that when combined withbone scintigraphy, technetium-99m HMPAO is useful in patients with Charcot arthropathy, taggedWBC scans can be falsely positive in the setting of other causes of inflammation including fracture[52]. False-negative results are possible in the setting of chronic osteomyelitis when white cellmigration to sites of infection is decreased.

Gallium and dual tracer scans – Gallium scans utilize the affinity of gallium-67 to acute phasereactants (lactoferrin, transferrin, and others) to demonstrate areas of inflammation that may berelated to infection [51]. This older modality is used less commonly than the other nuclear modalitiesdescribed above [46].

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This method is quite sensitive and more specific than three-phase bone scan (sensitivity andspecificity 25 to 80 and 67 percent, respectively) [53,54]. If negative, gallium scans effectivelyexclude the diagnosis of osteomyelitis [1]. False-positive results can occur in the setting of uptakerelated to fracture and neoplasm; correlative radiographs may help to evaluate for these entities. Atpresent, gallium imaging is limited primarily to the spine [46].

Scanning is typically performed 18 to 72 hours following gallium injection and therefore should bereserved for patients who are clinically stable and do not require prompt imaging results for urgentmanagement decisions [17].

A gallium scan can be performed concurrently with a technetium-labeled three-phase bone scan,and the information gathered may be more useful than that obtained from either examination alone[54]. In this instance, both radionuclide species are injected at the same time. Then, bone scanimages can be obtained three to four hours after injection, and gallium scan images can be obtainedup to 24 hours later. The result is considered positive when gallium tracer uptake is greater than thatof the bone scan.

SPECT-CT – Single photon emission CT (SPECT-CT) has been shown to increase the accuracy ofgallium studies, tagged WBC studies, and three-phase bone scans. Improved localization of the siteof osteomyelitis and, more importantly, improved distinction between soft tissue infection andosteomyelitis have been reported [55]. The use of SPECT-CT has also shown to improve theaccuracy of tagged WBC studies in post-traumatic osteomyelitis [49]. CT has been shown toincrease the accuracy of gallium studies, tagged WBC studies, and three-phase bone scans. Thistool allows improved distinction between soft tissue infection and osteomyelitis as well as improvedlocalization of osteomyelitis [55].

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cortical surface of the bone reflects the acoustic energy that is used to generate ultrasound images.However, changes superficial to cortical bone can be visualized by ultrasound.

In osteomyelitis, ultrasound can demonstrate elevation and/or thickening of the periosteum due to pusemanating from the bone [56-58]. Ultrasound may be more useful for detection of these findings inpediatric patients, since the periosteum in the pediatric skeleton is more loosely adherent to the cortexthan in the adult skeleton [1,17]. Ultrasonography is considered excellent for aspirating suspectedinfected fluid collections or abscesses [59]. (See "Overview of the clinical manifestations of sickle celldisease" and "Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on'Ultrasonography'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around theworld are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infection inadults".)

SUMMARY

In general, if osteomyelitis is suspected based on clinical history and physical findings, imagingshould begin with conventional radiographs of the involved area for patients with at least two weeksof clinical symptoms. A more sophisticated imaging modality should be pursued for patients with lessthan two weeks of symptoms, normal radiographs, or radiographs suggestive of osteomyelitiswithout definitive characteristic features. In general, magnetic resonance imaging (MRI) is theimaging modality with greatest sensitivity for diagnosis of osteomyelitis; if MRI is not available orcontraindicated, computed tomography (CT) is an appropriate alternative test. If metal hardwareprecludes MRI or CT, a nuclear study is appropriate. (See 'Selecting an imaging modality' above and"Osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Clinical approach'.)

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In the setting of osteomyelitis, inflammatory exudate in the marrow causes elevated medullarypressure, which compresses vascular channels, leading to ischemia and bone necrosis. If the areasof necrotic bone separate from the remaining viable bone, sequestra are formed. Surviving bone andperiosteum ultimately produce a sheath of bone surrounding the area of necrosis, which is referredto as an involucrum. Both the sequestra and involucrum may be apparent radiographically. (See'Pathophysiology of osteomyelitis' above.)

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Findings of osteomyelitis on conventional radiography include osteopenia, cortical loss, bonydestruction, and periosteal reaction. Other chronic findings include reactive sclerosis, sequestra, andinvolucrum. Conventional radiographs are useful for identification of noninfectious pathology and foridentifying air within soft tissues. However, conventional radiography may be insufficient todistinguish osteomyelitis from other processes such as Charcot arthropathy and fracture. (See

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ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Dr. Perry Horwich and Dr. Mary Hochman,who contributed to earlier versions of this topic review.


'Conventional radiography' above.)

MRI has high sensitivity and negative predictive value for diagnosis of osteomyelitis. MRI maydemonstrate abnormal marrow edema as early as one to five days following onset of infection, andan MRI with no evidence of osteomyelitis is sufficient for exclusion of osteomyelitis in patients withsymptoms for at least one week. MRI is useful for delineating the extent of cortical destructioncharacteristic of osteomyelitis, as well as for detecting presence of bone marrow and soft tissueinflammation (such as in the setting of cellulitis, myositis, and/or ulceration). However, MRI mayoverestimate the extent and duration of infection and cannot reliably distinguish between marrowchanges attributable to infection and those attributable to other pathology. Intravenous gadoliniumcontrast does not improve the detection of acute osteomyelitis but does improve the distinctionbetween phlegmon, necrotic tissue, and abscess. (See 'Magnetic resonance imaging' above.)

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CT is more sensitive than conventional radiography for assessing cortical and trabecular integrity,periosteal reaction, intraosseous gas, soft tissue gas, and the extent of sinus tracts. It is the mostuseful modality to evaluate for the presence of osseous sequestra and involucrum. (See 'Computedtomography' above.)

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A nuclear study may be useful if metal hardware precludes MRI or CT. Nuclear imaging has highsensitivity for detecting evidence of inflammation and therefore tends to be more reliable forevaluation of acute infection than chronic infection. However, a major limitation is that radiographicevidence of bone turnover or inflammation due to noninfectious bone pathology may be confusedwith osteomyelitis. Single photon emission CT (SPECT-CT) has been shown to improve theaccuracy of tracer imaging alone. While fluorine-18-fluorodeoxyglucose positron emissiontomography CT may provide similar diagnostic accuracy as MRI, its high cost and lack of insurerreimbursement preclude routine use. Tagged white blood cell studies combined with three-phasebone scan or SPECT-CT are more practical choices. Single photon emission CT improves theaccuracy of tracer imaging alone. (See 'Nuclear modalities' above.)

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Ultrasound may be a useful diagnostic tool in circumstances where the more preferred modalitiesare not readily available. This may be especially true in the pediatric population. In addition,ultrasound is excellent for aspirating suspected infected fluid collections or abscesses. (See'Ultrasonography' above.)

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REFERENCES

1. Pineda C, Vargas A, Rodríguez AV. Imaging of osteomyelitis: current concepts. Infect Dis ClinNorth Am 2006; 20:789.


3. Schmitt SK. Osteomyelitis. Infect Dis Clin North Am 2017; 31:325.

4. Demirev A, Weijers R, Geurts J, et al. Comparison of [18 F]FDG PET/CT and MRI in the diagnosisof active osteomyelitis. Skeletal Radiol 2014; 43:665.

5. Expert Panel on Musculoskeletal Imaging:, Beaman FD, von Herrmann PF, et al. ACRAppropriateness Criteria(®) Suspected Osteomyelitis, Septic Arthritis, or Soft Tissue Infection(Excluding Spine and Diabetic Foot). J Am Coll Radiol 2017; 14:S326.

6. Lauri C, Tamminga M, Glaudemans AWJM, et al. Detection of Osteomyelitis in the Diabetic Foot byImaging Techniques: A Systematic Review and Meta-analysis Comparing MRI, White Blood CellScintigraphy, and FDG-PET. Diabetes Care 2017; 40:1111.

7. Harmer JL, Pickard J, Stinchcombe SJ. The role of diagnostic imaging in the evaluation ofsuspected osteomyelitis in the foot: a critical review. Foot (Edinb) 2011; 21:149.

8. Centre for Clinical Practice at NICE (UK). Diabetic Foot Problems: Inpatient Management of Diabetic Foot Problems, National Institute for Health and Clinical Excellence, London 2011.

9. Dinh MT, Abad CL, Safdar N. Diagnostic accuracy of the physical examination and imaging testsfor osteomyelitis underlying diabetic foot ulcers: meta-analysis. Clin Infect Dis 2008; 47:519.

10. Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. ClinInfect Dis 2004; 39:885.

11. Darouiche RO, Landon GC, Klima M, et al. Osteomyelitis associated with pressure sores. ArchIntern Med 1994; 154:753.

12. Gold RH, Hawkins RA, Katz RD. Bacterial osteomyelitis: findings on plain radiography, CT, MR,and scintigraphy. AJR Am J Roentgenol 1991; 157:365.

13. Bone and Joint Imaging, 3rd ed, Resnick D, Kransdorf M (Eds), Elsevier, Philadelphia 2005. p.718.

14. Butt WP. The radiology of infection. Clin Orthop Relat Res 1973; :20.

15. Berbari EF, Steckelberg JM, Osmon DR. Osteomyelitis. In: Principles and Practice of Infectious Diseases, 6th ed, Mandell GL, et al (Eds), Elsevier, Philadelphia 2005. p.1322.


























16. Kaim AH, Gross T, von Schulthess GK. Imaging of chronic posttraumatic osteomyelitis. Eur Radiol2002; 12:1193.

17. Simpfendorfer CS. Radiologic Approach to Musculoskeletal Infections. Infect Dis Clin North Am2017; 31:299.

18. American College of Radiology. ACR Approproateness Criteria. Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. https://acsearch.acr.org/docs/69340/Narrative/ (Accessed on September 04, 2018).

19. Hingorani A, LaMuraglia GM, Henke P, et al. The management of diabetic foot: A clinical practiceguideline by the Society for Vascular Surgery in collaboration with the American Podiatric MedicalAssociation and the Society for Vascular Medicine. J Vasc Surg 2016; 63:3S.

20. Peterson N, Widnall J, Evans P, et al. Diagnostic Imaging of Diabetic Foot Disorders. Foot Ankle Int2017; 38:86.

21. Erdman WA, Tamburro F, Jayson HT, et al. Osteomyelitis: characteristics and pitfalls of diagnosiswith MR imaging. Radiology 1991; 180:533.

22. Durham JR, Lukens ML, Campanini DS, et al. Impact of magnetic resonance imaging on themanagement of diabetic foot infections. Am J Surg 1991; 162:150.

23. Butalia S, Palda VA, Sargeant RJ, et al. Does this patient with diabetes have osteomyelitis of thelower extremity? JAMA 2008; 299:806.

24. Kapoor A, Page S, Lavalley M, et al. Magnetic resonance imaging for diagnosing foot osteomyelitis:a meta-analysis. Arch Intern Med 2007; 167:125.

25. American College of Radiology. ACR Appropriateness Criteria. ACR 2012.

26. Treglia G, Sadeghi R, Annunziata S, et al. Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related todiabetic foot: a systematic review and a meta-analysis. Foot (Edinb) 2013; 23:140.

27. Fujii M, Armstrong DG, Terashi H. Efficacy of magnetic resonance imaging in diagnosing diabeticfoot osteomyelitis in the presence of ischemia. J Foot Ankle Surg 2013; 52:717.

28. Tomas MB, Patel M, Marwin SE, Palestro CJ. The diabetic foot. Br J Radiol 2000; 73:443.

29. Ahmadi ME, Morrison WB, Carrino JA, et al. Neuropathic arthropathy of the foot with and withoutsuperimposed osteomyelitis: MR imaging characteristics. Radiology 2006; 238:622.

30. Abdel Razek AAK, Samir S. Diagnostic performance of diffusion-weighted MR imaging indifferentiation of diabetic osteoarthropathy and osteomyelitis in diabetic foot. Eur J Radiol 2017;






























89:221.

31. Shimose S, Sugita T, Kubo T, et al. Differential diagnosis between osteomyelitis and bone tumors.Acta Radiol 2008; 49:928.

32. Ledermann HP, Kaim A, Bongartz G, Steinbrich W. Pitfalls and limitations of magnetic resonanceimaging in chronic posttraumatic osteomyelitis. Eur Radiol 2000; 10:1815.

33. Mader JT, Ortiz M, Calhoun JH. Update on the diagnosis and management of osteomyelitis. ClinPodiatr Med Surg 1996; 13:701.

34. Wing VW, Jeffrey RB Jr, Federle MP, et al. Chronic osteomyelitis examined by CT. Radiology 1985;154:171.

35. Seltzer SE. Value of computed tomography in planning medical and surgical treatment of chronicosteomyelitis. J Comput Assist Tomogr 1984; 8:482.

36. Gross T, Kaim AH, Regazzoni P, Widmer AF. Current concepts in posttraumatic osteomyelitis: adiagnostic challenge with new imaging options. J Trauma 2002; 52:1210.

37. Al-Sheikh W, Sfakianakis GN, Mnaymneh W, et al. Subacute and chronic bone infections:diagnosis using In-111, Ga-67 and Tc-99m MDP bone scintigraphy, and radiography. Radiology1985; 155:501.

38. Kaim A, Maurer T, Ochsner P, et al. Chronic complicated osteomyelitis of the appendicularskeleton: diagnosis with technetium-99m labelled monoclonal antigranulocyte antibody-immunoscintigraphy. Eur J Nucl Med 1997; 24:732.

39. Kolindou A, Liu Y, Ozker K, et al. In-111 WBC imaging of osteomyelitis in patients with underlyingbone scan abnormalities. Clin Nucl Med 1996; 21:183.

40. Schauwecker DS. The scintigraphic diagnosis of osteomyelitis. AJR Am J Roentgenol 1992; 158:9.

41. Schauwecker DS. Osteomyelitis: diagnosis with In-111-labeled leukocytes. Radiology 1989;171:141.

42. Heiba SI, Kolker D, Mocherla B, et al. The optimized evaluation of diabetic foot infection by dualisotope SPECT/CT imaging protocol. J Foot Ankle Surg 2010; 49:529.

43. Keidar Z, Militianu D, Melamed E, et al. The diabetic foot: initial experience with 18F-FDG PET/CT.J Nucl Med 2005; 46:444.

44. Chacko TK, Zhuang H, Nakhoda KZ, et al. Applications of fluorodeoxyglucose positron emissiontomography in the diagnosis of infection. Nucl Med Commun 2003; 24:615.

45. Wang GL, Zhao K, Liu ZF, et al. A meta-analysis of fluorodeoxyglucose-positron emission


































tomography versus scintigraphy in the evaluation of suspected osteomyelitis. Nucl Med Commun2011; 32:1134.

46. Palestro CJ. Radionuclide imaging of osteomyelitis. Semin Nucl Med 2015; 45:32.

47. Termaat MF, Raijmakers PG, Scholten HJ, et al. The accuracy of diagnostic imaging for theassessment of chronic osteomyelitis: a systematic review and meta-analysis. J Bone Joint Surg Am2005; 87:2464.

48. Basu S, Chryssikos T, Houseni M, et al. Potential role of FDG PET in the setting of diabetic neuro-osteoarthropathy: can it differentiate uncomplicated Charcot's neuroarthropathy from osteomyelitisand soft-tissue infection? Nucl Med Commun 2007; 28:465.

49. Govaert GA, IJpma FF, McNally M, et al. Accuracy of diagnostic imaging modalities for peripheralpost-traumatic osteomyelitis - a systematic review of the recent literature. Eur J Nucl Med MolImaging 2017; 44:1393.

50. Schauwecker DS. The role of nuclear medicine in osteomyelitis. In: Skeletal Nuclear Medicine, Collier DB, et al (Eds), Mosby, St. Louis 1996.

51. Thrall J, Ziessman H. Nuclear Medicine: The Requisites, 2nd ed, Mosby, St. Louis 2001.

52. Poirier JY, Garin E, Derrien C, et al. Diagnosis of osteomyelitis in the diabetic foot with a 99mTc-HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy. Diabetes Metab2002; 28:485.

53. Palestro CJ, Kim CK, Swyer AJ, et al. Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy. J Nucl Med 1991;32:1861.

54. Tumeh SS, Aliabadi P, Weissman BN, McNeil BJ. Chronic osteomyelitis: bone and gallium scanpatterns associated with active disease. Radiology 1986; 158:685.

55. Saha S, Burke C, Desai A, et al. SPECT-CT: applications in musculoskeletal radiology. Br J Radiol2013; 86:20120519.

56. Abiri MM, Kirpekar M, Ablow RC. Osteomyelitis: detection with US. Radiology 1989; 172:509.

57. Howard CB, Einhorn M, Dagan R, Nyska M. Ultrasound in diagnosis and management of acutehaematogenous osteomyelitis in children. J Bone Joint Surg Br 1993; 75:79.

58. Wheat J. Diagnostic strategies in osteomyelitis. Am J Med 1985; 78:218.

59. Booz MM, Hariharan V, Aradi AJ, Malki AA. The value of ultrasound and aspiration in differentiatingvaso-occlusive crisis and osteomyelitis in sickle cell disease patients. Clin Radiol 1999; 54:636.































GRAPHICS

Summary statistics of imaging modalities for diagnosis of osteomyelitis associated withdiabetic foot ulcer

Diagnostic modalityTotal

patients

Sensitivity

(95% confidenceinterval)

Specificity

(95% confidenceinterval)

Study

Probe-to-bone test orexposed bone

288 0.60 (0.46-0.73) 0.91 (0.86-0.94) Dinh etal

Radiography 177 0.54 (0.44-0.63) 0.68 (0.53-0.80) Dinh etal

Magnetic resonance imaging 135

421

0.90 (0.82-0.95)

0.93 (0.82-0.97)

0.79 (0.62-0.91)

0.75 (0.63-0.84)

Dinh etal

Lauri etal

Bone scan 185 0.81 (0.73-0.87) 0.28 (0.17-0.42) Dinh etal

Leukocyte scan 269 0.74 (0.67-0.80) 0.68 (0.57-0.78) Dinh etal

In-111 oxine WBC 206 0.92 (0.72-0.98) 0.75 (0.66-0.82) Lauri etal

Tc-99m HMPAO WBC 406 0.91 (0.86-0.94) 0.92 (0.78-0.98) Lauri etal

18F-FDG PET/CT 254 0.89 (0.68-0.97) 0.92 (0.85-0.96) Lauri etal

WBC: white blood cell; HMPAO: hexamethylpropyleneamine oxime; 18F-FDG PET/CT: 18F-labeled fluoro-2-deoxyglucosepositron emission tomography/computed tomography.

Data reproduced with permission from: Dinh MT, Abad CL, Safdar N. Diagnostic accuracy of the physical examination andimaging tests for osteomyelitis underlying diabetic foot ulcers: Meta-analysis. Clin Infect Dis 2008; 47:519-527. Copyright ©2008 University of Chicago Press.With additional data from:

1. Lauri C, Tamminga M, Glaudemans AWJM. Detection of Osteomyelitis in the Diabetic Foot by Imaging Techniques: Asystematic Review and Meta-analysis Comparing MRI, White Blood Cell Scintigraphy, and FDG-PET. Diabetes Care 2017;40: 1111-1120.




Adult with chronic osteomyelitis

39-year-old man with chronic osteomyelitis of the tibia and a draining wound. Plain films (A andB) demonstrate a sclerotic sequestrum in the defect of the tibia (arrow). Magnetic resonanceimaging axial T1 & T2 images (C and D) show the sequestrum (arrow) in the intraosseousabscess. The abscess/sinus tract can be seen extending to the skin on the T2 image(arrowhead).

Courtesy of Charles Spritzer, MD.




Child with chronic osteomyelitis

Four-year-old boy with chronic osteomyelitis. Radiographs of the femurdemonstrate pathologic fracture and involucrum (arrow).

Courtesy of Charles Spritzer, MD.




Osteomyelitis of the toe

Radiograph of the foot demonstrates air in the soft tissues about the 5th toe(black arrowheads). Cortical destruction of the 5th metatarsal head is alsoseen (white arrow). Irregular contour of the overlying skin representsassociated soft tissue ulceration (asterisk).

Courtesy of Perry Horwich, MD.




Osteomyelitis of the patella

(A) Axial T1-weighted image demonstrates signal changes and corticalinterruption overlying the anterior and lateral patella. Patellar osteomyelitisis present (long arrow). Incidental note is made of an enchondroma(asterisk). (B) Axial short tau inversion recovery (STIR) image demonstrateshigh signal edema in the marrow of the anterior and lateral patella withoverlying soft tissue loss representing osteomyelitis (long arrow). A smallknee joint effusion is also present (arrowheads). (C,D) Pre- and postcontrastaxial images demonstrate enhancement in the distribution of edema in thepatella and overlying soft tissues. Patellar osteomyelitis is present in panel D(long arrow).





Osteomyelitis in the setting of a diabetic foot ulcer

(A) Sagittal fluid-sensitive short inversion time inversion recovery (STIR) imagedemonstrates high signal fluid collection along the plantar surface of the calcaneus(arrow).(B) Sagittal post-contrast T1-weighted image with fat saturation demonstrates theperipherally enhancing fluid collection (arrow).(C) Sagittal T1-weighted pre-contrast image demonstrates some cortical interruption(arrow).(D) Lateral radiograph demonstrates soft tissue loss overlying the plantar aspect ofthe calcaneus (arrow). Osseous remodeling and periosteal reaction about theposterior calcaneus (asterisk) reflect changes associated with longstanding chronicosteomyelitis.





Penumbra sign in osteomyelitis

Magnetic resonance imaging (MRI) scan shows the penumbra sign (atransitional zone with relatively high signal intensity between abscess andsclerotic bone marrow on T1-weighted MRI).

Reproduced with permission from: Shih HN, Shih LY, Wong YC. Diagnosis andtreatment of subacute osteomyelitis. J Trauma 2005; 58:83. Copyright © 2005Lippincott Williams & Wilkins.




Osteomyelitis in the heel

(A) Sagittal computed tomography image demonstrates cortical fragmentation of theplantar aspect of the calcaneus (arrows) and adjacent air and soft tissue ulceration.(B) Corresponding fluid-sensitive short inversion time inversion recovery (STIR)image demonstrates extensive high-signal edema in the calcaneus (asterisk) and againdemonstrates posterior plantar ulcer overlying the calcaneus (arrow).





Osteomyelitis in the setting of hip prosthesis

(A) Coronal-reformatted computed tomography image demonstrates markedbeam hardening artifact about a metallic left hip prosthesis (arrow).(B) Despite extensive artifact in image A, on lung windows, a region of aircan be identified adjacent to the lesser trochanter (arrow).(C) Fluoroscopic-guided aspiration (arrow indicates needle) yielded 3 cc ofpus. Initial Gram stain was positive for gram-negative rods; culturessubsequently grew Bacteroides fragilis.




Charles E Spritzer, MD Nothing to disclose Denis Spelman, MBBS, FRACP, FRCPA, MPH Nothing todisclose Elinor L Baron, MD, DTMH Nothing to disclose







Charles E Spritzer, MD Nothing to disclose Denis Spelman, MBBS, FRACP, FRCPA, MPH Nothing todisclose Elinor L Baron, MD, DTMH Nothing to disclose




Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology - UpToDate



Hematogenous osteomyelitis in children: Epidemiology,pathogenesis, and microbiologyAuthor: Paul Krogstad, MD Section Editors: Sheldon L Kaplan, MD, William A Phillips, MD Deputy Editor: Mary M Torchia,MD


Literature review current through: Feb 2020. | This topic last updated: Nov 18, 2019.

INTRODUCTION

Osteomyelitis is an infection localized to bone. It is usually caused by microorganisms (predominantlybacteria) that enter the bone hematogenously. Other pathogenic mechanisms include direct inoculation(usually traumatic, but also surgical) or local invasion from a contiguous infection (eg, cellulitis, sinusitis,periodontal disease). Other risk factors for nonhematogenous osteomyelitis include open fractures thatrequire surgical reduction, implanted orthopedic hardware (such as pins or screws), and puncturewounds.

The epidemiology, pathogenesis, and microbiology of hematogenous osteomyelitis in children will bediscussed here. The clinical features, evaluation, diagnosis, and management of osteomyelitis in childrenare discussed separately:

EPIDEMIOLOGY

The incidence of osteomyelitis varies geographically. As summarized in a 2012 systematic review andmeta-analysis that included >12,000 patients, the incidence ranged from approximately 1 in 5000 to 7700children in developed countries and 1 in 500 to 2300 children in developing countries [1]. Some countrieshave noted a decrease in the incidence over time [2], whereas others, including the United States, havenoted an increase, particularly with the emergence of community-associated methicillin-resistantStaphylococcus aureus [3,4].

Hematogenous osteomyelitis is more common in children than in adults. Boys are affected nearly twice

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(See "Hematogenous osteomyelitis in children: Clinical features and complications".)●

(See "Hematogenous osteomyelitis in children: Evaluation and diagnosis".)●

(See "Hematogenous osteomyelitis in children: Management".)●

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as often as girls [1]. More than one-half of pediatric cases occur in children younger than five years andone-quarter in children younger than two years [5]. However, osteomyelitis is uncommon in young infants(<4 months) without underlying risk factors [6]. (See 'Risk factors' below.)

RISK FACTORS

Risk factors for osteomyelitis in neonates (<30 days of age) include [6-8]:

Risk factors for hematogenous osteomyelitis in older infants and children include:

PATHOGENESIS

Overview — Hematogenous osteomyelitis in long (tubular) bones begins with bacterial deposition in themetaphysis (figure 1). The mechanism of deposition is unclear, although some evidence suggests thatendothelial cells permit microbial passage [10-12]. Trauma or emboli may cause occlusion of the slow-flowing sinusoidal vessels, further establishing a nidus for infection.

The focus of infection in the metaphysis leads to cellulitis in the bone marrow. Inflammatory exudate inthe marrow causes increased intramedullary pressure, which forces the exudate through the Haversiansystems and Volkmann canals and into the cortex, where it can rupture through the periosteum. Areas ofbone necrosis may develop at foci of infection within the bone. The resulting devitalized bone (known asa sequestrum) can be visualized radiographically and may be surrounded by new bone laid down by theelevated periosteum (known as the involucrum). Infection can spread to the epiphysis and adjacent jointspace; contiguous extension into the joint space occurs in as many as one-third of cases overall [1,9,13-

Complicated delivery●

Prematurity●

Skin infection●

Central venous catheter●

Urinary tract anomalies●

Active maternal infection at the time of delivery [9]●

Sickle cell disease (see "Acute and chronic bone complications of sickle cell disease", section on'Osteomyelitis and septic arthritis')

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Immunodeficiency disorders, such as chronic granulomatous disease (see "Chronic granulomatousdisease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infections')

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15].

Subacute/chronic osteomyelitis is sometimes associated with the formation of an intraosseous abscess(Brodie abscess), a central area of suppuration and necrosis contained and encapsulated by granulationtissue and sclerosis (image 1) [16,17]. (See "Osteomyelitis in adults: Clinical manifestations anddiagnosis", section on 'Hematogenous osteomyelitis'.)

Age-specific features — The pathogenesis of osteomyelitis in children is influenced by characteristics ofthe growing skeleton (figure 2) [18].

Birth to three months — Three features of the young infant skeleton facilitate the spread of boneinfection [18]:

Older infants and toddlers — The developing skeleton in older infants and toddlers is better able tocontain bone infection:

Older children and adolescents — In older children and adolescents, the metaphyseal cortex isconsiderably thicker, with a dense, fibrous periosteum. These features help to contain the infection, whichrarely ruptures to spread to the outer cortex. In adolescents, this may result in an intraosseous abscessin which a central area of suppuration and necrosis is contained and encapsulated by granulation tissue

The thin cortex and loosely applied periosteum are poorly able to contain infection, which can extendalong the subperiosteal space and break through into the surrounding soft tissue

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Nutrient metaphyseal capillaries perforate the epiphyseal growth plate, particularly in the hip,shoulder, and knee; these capillaries may permit spread of infection to the epiphysis and jointsurface, causing concomitant septic arthritis

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The capsule of the diarthrodial joints frequently extends to, or is slightly distal to, the epiphysealplate, allowing infection to invade the joint space and causing concomitant septic arthritis from afocus of osteomyelitis either proximal or distal to the joint (see "Bacterial arthritis: Epidemiology,pathogenesis, and microbiology in infants and children", section on 'Pathogenesis')

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As the skeleton matures, the cortex becomes thicker and the periosteum slightly more dense.Infection rarely spreads to the soft tissues, but subperiosteal abscess and contiguous edema readilydevelop; subperiosteal abscess typically occurs at the metaphysis, where the cortex is the thinnest[19].

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Metaphyseal capillaries atrophy as the epiphysis becomes ossified and a distinct physeal plate isformed. This process begins as early as eight months of age, is usually complete by 18 months, andhas traditionally been considered to limit the spread of infection to the joint space [20], unless themetaphysis is intracapsular, as it is in the shoulder, ankle, hip, and elbow. However, concurrentseptic arthritis and osteomyelitis are now commonly encountered [21,22], and transphyseal vesselsare of unclear importance.

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(Brodie abscess (image 1)). (See "Osteomyelitis in adults: Clinical manifestations and diagnosis", sectionon 'Hematogenous osteomyelitis'.)

Vertebral osteomyelitis — Vertebral infections can involve either the intervertebral disc (discitis) or thevertebral body. In young children, the blood supply to the intervertebral disc is rich, derived fromperiosteal vessels and adjacent vertebral bodies. The vessels from adjacent vertebrae begin to atrophy inthe first year of life and are obliterated completely by 10 years of age [23,24]. This may account for theobservation that discitis is more common in younger children [25]. (See "Hematogenous osteomyelitis inchildren: Clinical features and complications", section on 'Spine'.)

The pathogenesis of vertebral osteomyelitis may be related to sluggish blood flow and thrombosis in thevertebral veins. It is discussed separately. (See "Vertebral osteomyelitis and discitis in adults", section on'Pathogenesis'.)

MICROBIOLOGY

Most cases of acute hematogenous osteomyelitis in children are caused by gram-positive bacteria,principally S. aureus (table 1) [1]. However, no pathogen is isolated in routine cultures of blood andwound aspirates in up to one-half of cases [1], which usually are presumed to be caused by S. aureusand treated accordingly [26,27]. In younger children, many of these may actually be due to Kingellakingae. (See 'Kingella kingae' below and "Hematogenous osteomyelitis in children: Management",section on 'Culture-negative osteomyelitis'.)

Most cases of acute hematogenous osteomyelitis are caused by a single organism. Polymicrobialinfections usually are associated with contiguous spread, trauma, vascular insufficiency, or immobility ofan extremity. (See 'Polymicrobial infections' below.)

Staphylococcus — S. aureus is the most common cause of osteomyelitis in children overall. In a 2012systematic review, it was identified in approximately two-thirds of cases occurring since 1996 [1]. Thehigh frequency of S. aureus may be related to a number of extracellular and cell-associated virulencefactors that promote bacterial adherence, resistance to host defense mechanisms, and proteolyticactivity.

Although the prevalence of community-associated methicillin-resistant S. aureus (CA-MRSA) variesgeographically, it is an important cause of pediatric musculoskeletal infections. CA-MRSA is associatedwith more severe infection than methicillin-susceptible S. aureus (MSSA) [28-30]. In a retrospectivereview of 59 children with S. aureus osteomyelitis evaluated at a single center between 2000 and 2002,CA-MRSA was identified from blood or bone cultures in 31 individuals (53 percent) [31]. PVL positivitywas more frequent in MRSA than MSSA isolates (87 versus 24 percent), and all children who developedcomplications had PVL-positive isolates. However, in a more recent review of 287 children with S. aureusacute hematogenous osteoarticular infections from the same institution, agr group III S. aureus wasassociated with increased risk of orthopedic complications (22 versus 9 percent), while PVL positivity was






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not a predictor [22]. Additional reports also suggest that multifocal disease, local abscess formation,venous thrombosis, and a greater systemic inflammatory response are more common with PVL-positiveisolates [32-36]. However, osteomyelitis, pneumonia, and other severe manifestations can bedemonstrated in the absence of PVL, likely reflecting the presence of multiple virulence factorselaborated by S. aureus, particularly the USA300 strains that now predominate in the United States [32-36]. (See "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinicalspectrum", section on 'CA-MRSA strains'.)

Coagulase-negative staphylococci may cause osteomyelitis in neonates and children with indwellingvascular catheters (eg, for chronic hemodialysis). (See "Hematogenous osteomyelitis in children: Clinicalfeatures and complications", section on 'Chronic hemodialysis'.)

Groups A and B streptococci — Group A beta-hemolytic Streptococcus (Streptococcus pyogenes) maycause osteomyelitis in older infants and children, particularly as a complication of varicella-zoster virusinfection [37]. In a 2012 systematic review, group A beta-hemolytic Streptococcus was identified inapproximately 8 percent of cases occurring after 1996 [1].

Group B Streptococcus causes osteomyelitis in infants younger than three months. In a 2012 systematicreview, group B Streptococcus was identified in approximately 4 percent of cases occurring after 1996[1]. Infants with group B streptococcal osteomyelitis are usually two to four weeks of age. Generally,there is no recognized preceding infection and a single bone is involved. (See "Group B streptococcalinfection in neonates and young infants", section on 'Other focal infection'.)

Streptococcus pneumoniae — Streptococcus pneumoniae (pneumococcus) may cause osteomyelitisin children who are at increased risk of invasive pneumococcal disease (eg, those with chronic heartdisease, chronic lung disease, diabetes mellitus, sickle cell disease, asplenia, splenic dysfunction,immunodeficiency), including children younger than two years who are incompletely immunized againstS. pneumoniae. However, in the post-pneumococcal conjugate vaccine era, most cases occur in childrenwithout risk factors and are caused by serotypes not included in the 13-valent pneumococcal conjugatevaccine (especially 35B and 33F) [38].

Kingella kingae — K. kingae, a gram-negative organism present in oral microbiome, is beingincreasingly identified as a cause of osteomyelitis in children 6 to 36 months of age [9,39-42], and somereports suggest K. kingae is the most common cause of osteomyelitis in Switzerland and France [9,42-44]. It often affects nontubular bones (eg, sternum, vertebrae, calcaneum) [40].

K. kingae is a fastidious organism that is difficult to isolate by conventional culture techniques. Inoculationof specimens into blood culture vials and, especially, molecular diagnostic methods (eg, polymerasechain reaction amplification) may increase detection [40-42,45].

The epidemiology of skeletal infections caused by K. kingae was described in a cluster of cases inchildren attending a day care center [46]. Within a one-week period, three children aged 17 to 21 monthsattending the same classroom developed hematogenous osteomyelitis and septic arthritis. Child-to-child





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transmission was supported by identical patterns on pulse field gel electrophoresis and the increasedprevalence of nasal carriage among children in the index classroom compared with children in otherclassrooms (45 versus 7 percent).

Escherichia coli and other coliforms — E. coli and other coliforms can cause osteomyelitis inneonates. In a 2012 systematic review, E. coli was identified in approximately 2 percent of casesoccurring after 1996 [1].

Haemophilus influenzae — Haemophilus influenzae type b (Hib) is a rare cause of osteomyelitis nowthat infants are routinely vaccinated against Hib [3,47,48].

Other bacteria — Other bacteria that can cause osteomyelitis include:

Bartonella henselae osteomyelitis may occur in children with cat scratch disease [49-52]. In aliterature review of 64 cases of B. henselae osteomyelitis, the vertebral column and pelvic girdlewere the most frequent sites of infection; approximately one-third of patients had multifocal disease,with involvement of ≥3 bones [52]. (See "Microbiology, epidemiology, clinical manifestations, anddiagnosis of cat scratch disease".)

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Pseudomonas aeruginosa is a cause of osteomyelitis in injection drug users. It also may occur inchildren with nail puncture wounds to the foot. (See "Pseudomonas aeruginosa skin and soft tissueinfections", section on 'Infection following nail puncture'.)

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Brucella osteomyelitis may occur in children with travel to or living in an endemic area and in childrenwho ingest unpasteurized dairy products. Brucella can produce abscesses in the vertebral bodies orlong bones, although bone involvement is not a striking feature of the disease. (See "Brucellosis:Epidemiology, microbiology, clinical manifestations, and diagnosis".)

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Mycobacterium tuberculosis and nontuberculous mycobacteria can cause hematogenousosteomyelitis in children with immunodeficiency, penetrating injuries, or surgical history. (See"Skeletal tuberculosis" and "Epidemiology, clinical manifestations, and diagnosis of osteomyelitis dueto nontuberculous mycobacteria" and "Treatment of osteomyelitis due to nontuberculousmycobacteria in adults".)

●

Salmonella species – Salmonella species may cause osteomyelitis in children with sickle celldisease or related hemoglobinopathies, exposure to reptiles or amphibians, gastrointestinalsymptoms, and children in developing countries.

●

Actinomyces may cause osteomyelitis in facial bones or vertebral bodies [53]. (See "Cervicofacialactinomycosis".)

●

Anaerobic organisms rarely cause osteomyelitis, which most often results from spread of infectionfrom the paranasal sinuses (eg, Pott puffy tumor) or devitalized tissue. However, primaryFusobacterium osteomyelitis with concomitant septic arthritis has been described [54,55].

●


https://www.uptodate.com/contents/hematogenous-osteomyelitis-in-children-epidemiology-pathogenesis-and-microbiology/abstract/3,47,48



https://www.uptodate.com/contents/microbiology-epidemiology-clinical-manifestations-and-diagnosis-of-cat-scratch-disease?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/microbiology-epidemiology-clinical-manifestations-and-diagnosis-of-cat-scratch-disease?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/pseudomonas-aeruginosa-skin-and-soft-tissue-infections?sectionName=INFECTION+FOLLOWING+NAIL+PUNCTURE&search=osteomyelitis&topicRef=6063&anchor=H12&source=see_link#H12


https://www.uptodate.com/contents/brucellosis-epidemiology-microbiology-clinical-manifestations-and-diagnosis?search=osteomyelitis&topicRef=6063&source=see_link


https://www.uptodate.com/contents/skeletal-tuberculosis?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-osteomyelitis-due-to-nontuberculous-mycobacteria?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-osteomyelitis-due-to-nontuberculous-mycobacteria?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/treatment-of-osteomyelitis-due-to-nontuberculous-mycobacteria-in-adults?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/treatment-of-osteomyelitis-due-to-nontuberculous-mycobacteria-in-adults?search=osteomyelitis&topicRef=6063&source=see_link


https://www.uptodate.com/contents/cervicofacial-actinomycosis?search=osteomyelitis&topicRef=6063&source=see_link

https://www.uptodate.com/contents/cervicofacial-actinomycosis?search=osteomyelitis&topicRef=6063&source=see_link




Fungi — Coccidiomycosis, which is increasingly common in the southwestern United States, can causeinfection in cancellous bone such as vertebral bodies, distal tubular bones, and the skull [56]. Infection inmultiple sites occurs in nearly one-half of all children and adults with musculoskeletal coccidioidomycosis[57-59]. (See "Manifestations and treatment of nonmeningeal extrathoracic coccidioidomycosis", sectionon 'Clinical manifestations'.)

Bone disease caused by Aspergillus has been described in immunocompetent individuals [60].Aspergillus is frequently a cause of osteomyelitis in patients with chronic granulomatous disease [61].

Polymicrobial infections — Polymicrobial infection is unusual in children with acute osteomyelitis [62].Isolation of multiple bacteria from bone generally occurs with spread from a contiguous infectious focus,usually from the skull, face, hands, or feet. Distal extremities that are compromised by vascularinsufficiency or are immobile, as in patients with paraplegia, spina bifida, or following trauma such aslawn mower injuries, can be sites of polymicrobial osteomyelitis.

Pathogens in abnormal hosts


Links to society and government-sponsored guidelines from selected countries and regions around theworld are provided separately. (See "Society guideline links: Septic arthritis and osteomyelitis inchildren".)

SUMMARY

Sickle cell disease – Among patients with sickle cell disease, hematogenous osteomyelitis is mostoften caused by Salmonella species or other gram-negative organisms, such as E. coli [63-70]. S.aureus, the most common cause of osteomyelitis in normal hosts, probably accounts for only one-fourth of all cases in sickle cell disease. (See "Acute and chronic bone complications of sickle celldisease".)

●

Chronic granulomatous disease – Children with chronic granulomatous disease most oftendevelop osteomyelitis caused by Serratia and Aspergillus species. Osteomyelitis is less oftenattributed to staphylococci, Pseudomonas, Burkholderia, Nocardia, and other bacterial and fungalspecies. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, anddiagnosis", section on 'Infections'.)

●

HIV – Osteomyelitis in patients with human HIV infection is most commonly caused by S. aureus. S.pneumoniae infections are also particularly common in HIV-infected children who have not beenimmunized [71]. Other organisms that have been recovered in individual cases include E. coli,Salmonella enteritidis, Cryptococcus neoformans, Mycobacterium kansasii, and Histoplasmacapsulatum.

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https://www.uptodate.com/contents/manifestations-and-treatment-of-nonmeningeal-extrathoracic-coccidioidomycosis?sectionName=CLINICAL+MANIFESTATIONS&search=osteomyelitis&topicRef=6063&anchor=H4&source=see_link#H4

https://www.uptodate.com/contents/manifestations-and-treatment-of-nonmeningeal-extrathoracic-coccidioidomycosis?sectionName=CLINICAL+MANIFESTATIONS&search=osteomyelitis&topicRef=6063&anchor=H4&source=see_link#H4




https://www.uptodate.com/contents/society-guideline-links-septic-arthritis-and-osteomyelitis-in-children?search=osteomyelitis&topicRef=6063&source=see_link



https://www.uptodate.com/contents/acute-and-chronic-bone-complications-of-sickle-cell-disease?search=osteomyelitis&topicRef=6063&source=see_link








The incidence of pediatric osteomyelitis varies geographically and is greater in developing thandeveloped countries. Most cases occur in children younger than five years. Boys are affectedapproximately twice as often as girls. (See 'Epidemiology' above.)

●

Risk factors for osteomyelitis in neonates include complicated delivery, prematurity, skin infection,central venous catheter, and urinary tract anomalies. Risk factors for osteomyelitis in older infantsand children include sickle cell disease, immunodeficiency, sepsis, minor trauma with coincidentbacteremia, and indwelling vascular catheter (including hemodialysis catheters). (See 'Risk factors'above.)

●

The pathogenesis of hematogenous osteomyelitis involves deposition of bacteria in the metaphysis(from the metaphyseal vessels) leading to cellulitis of the bone marrow; the exudate under pressureis forced into the bony cortex, where it can lift or rupture through the periosteum (figure 1). Thespread of infection is influenced by characteristics of the growing skeleton (figure 2) (see'Pathogenesis' above):

●

In the young infant, the thin cortex and loosely applied periosteum are poorly able to containinfection, which can extend into the surrounding soft tissue. The metaphyseal blood supply,which crosses the epiphyseal growth plate, permits spread of infection to the epiphysis and jointspace. (See 'Birth to three months' above.)

•

In older infants, children, and adolescents, the thicker cortex, denser periosteum, and atrophy ofthe metaphyseal capillaries prevent spread of infection to the soft tissues and epiphysis.However, joint infection may still occur if the metaphysis is intracapsular (eg, shoulder, hip,ankle, elbow) or with simultaneous hematogenous infection. Subperiosteal abscess typicallyoccurs at the metaphysis. (See 'Older infants and toddlers' above and 'Older children andadolescents' above.)

•

Most cases of acute hematogenous osteomyelitis are caused by a single organism. However, nopathogen is isolated in approximately one-half of cases. Polymicrobial infections usually areassociated with contiguous spread, trauma, vascular insufficiency, or immobility of an extremity.(See 'Microbiology' above.)

●

Staphylococcus aureus is the most common cause of osteomyelitis in children. Community-associated methicillin-resistant S. aureus is associated with more severe infection than methicillin-sensitive S. aureus. (See 'Staphylococcus' above.)

●

Other important bacterial causes of hematogenous osteomyelitis in children include groups A and BStreptococcus, Streptococcus pneumoniae, and Kingella kingae (the dominant cause ofosteoarticular infections in several countries) (table 1). (See 'Microbiology' above.)

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REFERENCES

1. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatricosteomyelitis: a systematic review of the literature. J Bone Joint Surg Br 2012; 94:584.

2. Blyth MJ, Kincaid R, Craigen MA, Bennet GC. The changing epidemiology of acute and subacutehaematogenous osteomyelitis in children. J Bone Joint Surg Br 2001; 83:99.

3. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitisand septic arthritis: emergence of community-associated methicillin-resistant Staphylococcusaureus. J Pediatr Orthop 2006; 26:703.

4. Malcius D, Trumpulyte G, Barauskas V, Kilda A. Two decades of acute hematogenousosteomyelitis in children: are there any changes? Pediatr Surg Int 2005; 21:356.

5. Gutierrez K. Bone and joint infections in children. Pediatr Clin North Am 2005; 52:779.

6. Wong M, Isaacs D, Howman-Giles R, Uren R. Clinical and diagnostic features of osteomyelitisoccurring in the first three months of life. Pediatr Infect Dis J 1995; 14:1047.

7. Knudsen CJ, Hoffman EB. Neonatal osteomyelitis. J Bone Joint Surg Br 1990; 72:846.

8. de Jesus LE, Fernandes A, Sias SM, et al. Neonatal osteomyelitis and complex nephro-ureteralduplication. Surg Infect (Larchmt) 2011; 12:73.

9. Ferroni A, Al Khoury H, Dana C, et al. Prospective survey of acute osteoarticular infections in aFrench paediatric orthopedic surgery unit. Clin Microbiol Infect 2013; 19:822.

10. Ham KN, Hurley JV, Ryan GB, Storey E. Localization of particulate carbon in metaphyseal vesselsof growing rats. Aust J Exp Biol Med Sci 1965; 43:625.

11. Anderson CE, Parker J. Invasion and resorption in enchondral ossification. An electron microscopicstudy. J Bone Joint Surg Am 1966; 48:899.

12. Emslie KR, Nade S. Pathogenesis and treatment of acute hematogenous osteomyelitis: evaluationof current views with reference to an animal model. Rev Infect Dis 1986; 8:841.

13. Yagupsky P, Bar-Ziv Y, Howard CB, Dagan R. Epidemiology, etiology, and clinical features ofseptic arthritis in children younger than 24 months. Arch Pediatr Adolesc Med 1995; 149:537.

14. Perlman MH, Patzakis MJ, Kumar PJ, Holtom P. The incidence of joint involvement with adjacentosteomyelitis in pediatric patients. J Pediatr Orthop 2000; 20:40.






























15. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Shortened hospital stay for childhood bone and jointinfections: analysis of 265 prospectively collected culture-positive cases in 1983-2005. Scand JInfect Dis 2012; 44:683.

16. Ramos OM. Chronic osteomyelitis in children. Pediatr Infect Dis J 2002; 21:431.

17. Foster CE, Taylor M, Schallert EK, et al. Brodie Abscess in Children: A 10-Year Single InstitutionRetrospective Review. Pediatr Infect Dis J 2019; 38:e32.

18. Ogden JA. Pediatric osteomyelitis and septic arthritis: the pathology of neonatal disease. Yale JBiol Med 1979; 52:423.

19. Green WT. Osteomyelitis of infants: A disease different from osteomyelitis of older children. ArchSurg 1936; 32:462.

20. Trueta J. The three types of acute hematogenous osteomyelitis: A clinical and vascular study. JBone Joint Surg Br 1959; 41:671.

21. Montgomery CO, Siegel E, Blasier RD, Suva LJ. Concurrent septic arthritis and osteomyelitis inchildren. J Pediatr Orthop 2013; 33:464.

22. McNeil JC, Vallejo JG, Kok EY, et al. Clinical and Microbiologic Variables Predictive of OrthopedicComplications Following Staphylococcus aureus Acute Hematogenous Osteoarticular Infections inChildren. Clin Infect Dis 2019; 69:1955.

23. Conventry MB, Ghormley RK, Kernohan JW. Intervertebral disc: Its microscopic anatomy andpathology. J Bone Joint Surg 1945; 27:105.

24. Cushing AH. Diskitis in children. Clin Infect Dis 1993; 17:1.

25. Fernandez M, Carrol CL, Baker CJ. Discitis and vertebral osteomyelitis in children: an 18-yearreview. Pediatrics 2000; 105:1299.

26. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Significance of Negative Cultures in the Treatment ofAcute Hematogenous Bone and Joint Infections in Children. J Pediatric Infect Dis Soc 2013; 2:119.

27. Floyed RL, Steele RW. Culture-negative osteomyelitis. Pediatr Infect Dis J 2003; 22:731.

28. Sarkissian EJ, Gans I, Gunderson MA, et al. Community-acquired Methicillin-resistantStaphylococcus aureus Musculoskeletal Infections: Emerging Trends Over the Past Decade. JPediatr Orthop 2016; 36:323.

29. Davis WT, Gilbert SR. Comparison of Methicillin-resistant Versus Susceptible Staphylococcusaureus Pediatric Osteomyelitis. J Pediatr Orthop 2018; 38:e285.

30. Vorhies JS, Lindsay EA, Tareen NG, et al. Severity Adjusted Risk of Long-term Adverse Sequelae


































Among Children With Osteomyelitis. Pediatr Infect Dis J 2019; 38:26.

31. Martínez-Aguilar G, Avalos-Mishaan A, Hulten K, et al. Community-acquired, methicillin-resistantand methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children. PediatrInfect Dis J 2004; 23:701.

32. Gonzalez BE, Martinez-Aguilar G, Hulten KG, et al. Severe Staphylococcal sepsis in adolescents inthe era of community-acquired methicillin-resistant Staphylococcus aureus. Pediatrics 2005;115:642.

33. Bocchini CE, Hulten KG, Mason EO Jr, et al. Panton-Valentine leukocidin genes are associatedwith enhanced inflammatory response and local disease in acute hematogenous Staphylococcusaureus osteomyelitis in children. Pediatrics 2006; 117:433.

34. Gonzalez BE, Teruya J, Mahoney DH Jr, et al. Venous thrombosis associated with staphylococcalosteomyelitis in children. Pediatrics 2006; 117:1673.

35. McCaskill ML, Mason EO Jr, Kaplan SL, et al. Increase of the USA300 clone among community-acquired methicillin-susceptible Staphylococcus aureus causing invasive infections. Pediatr InfectDis J 2007; 26:1122.

36. Ritz N, Curtis N. The role of Panton-Valentine leukocidin in Staphylococcus aureus musculoskeletalinfections in children. Pediatr Infect Dis J 2012; 31:514.

37. Ibia EO, Imoisili M, Pikis A. Group A beta-hemolytic streptococcal osteomyelitis in children.Pediatrics 2003; 112:e22.

38. Olarte L, Romero J, Barson W, et al. Osteoarticular Infections Caused by Streptococcuspneumoniae in Children in the Post-Pneumococcal Conjugate Vaccine Era. Pediatr Infect Dis J2017; 36:1201.

39. Yagupsky P, Porsch E, St Geme JW 3rd. Kingella kingae: an emerging pathogen in young children.Pediatrics 2011; 127:557.

40. Chometon S, Benito Y, Chaker M, et al. Specific real-time polymerase chain reaction placesKingella kingae as the most common cause of osteoarticular infections in young children. PediatrInfect Dis J 2007; 26:377.

41. El Houmami N, Minodier P, Dubourg G, et al. Patterns of Kingella kingae Disease Outbreaks.Pediatr Infect Dis J 2016; 35:340.

42. Samara E, Spyropoulou V, Tabard-Fougère A, et al. Kingella kingae and Osteoarticular Infections.Pediatrics 2019; 144.

43. Ceroni D, Kampouroglou G, Valaikaite R, et al. Osteoarticular infections in young children: what has



































changed over the last years? Swiss Med Wkly 2014; 144:w13971.

44. Juchler C, Spyropoulou V, Wagner N, et al. The Contemporary Bacteriologic Epidemiology ofOsteoarticular Infections in Children in Switzerland. J Pediatr 2018; 194:190.

45. Verdier I, Gayet-Ageron A, Ploton C, et al. Contribution of a broad range polymerase chain reactionto the diagnosis of osteoarticular infections caused by Kingella kingae: description of twenty-fourrecent pediatric diagnoses. Pediatr Infect Dis J 2005; 24:692.

46. Kiang KM, Ogunmodede F, Juni BA, et al. Outbreak of osteomyelitis/septic arthritis caused byKingella kingae among child care center attendees. Pediatrics 2005; 116:e206.

47. De Jonghe M, Glaesener G. [Type B Haemophilus influenzae infections. Experience at thePediatric Hospital of Luxembourg]. Bull Soc Sci Med Grand Duche Luxemb 1995; 132:17.

48. Ratnayake K, Davis AJ, Brown L, Young TP. Pediatric acute osteomyelitis in the postvaccine,methicillin-resistant Staphylococcus aureus era. Am J Emerg Med 2015; 33:1420.

49. Sakellaris G, Kampitakis E, Karamitopoulou E, et al. Cat scratch disease simulating a malignantprocess of the chest wall with coexistent osteomyelitis. Scand J Infect Dis 2003; 35:433.

50. Mirakhur B, Shah SS, Ratner AJ, et al. Cat scratch disease presenting as orbital abscess andosteomyelitis. J Clin Microbiol 2003; 41:3991.

51. Hajjaji N, Hocqueloux L, Kerdraon R, Bret L. Bone infection in cat-scratch disease: a review of theliterature. J Infect 2007; 54:417.

52. Erdem G, Watson JR, Hunt WG, et al. Clinical and Radiologic Manifestations of Bone Infection inChildren with Cat Scratch Disease. J Pediatr 2018; 201:274.

53. Bartkowski SB, Zapala J, Heczko P, Szuta M. Actinomycotic osteomyelitis of the mandible: reviewof 15 cases. J Craniomaxillofac Surg 1998; 26:63.

54. Gregory SW, Boyce TG, Larson AN, et al. Fusobacterium nucleatum Osteomyelitis in 3 PreviouslyHealthy Children: A Case Series and Review of the Literature. J Pediatric Infect Dis Soc 2015;4:e155.

55. Brook I. Microbiology and management of joint and bone infections due to anaerobic bacteria. JOrthop Sci 2008; 13:160.

56. Galgiani JN, Ampel NM, Catanzaro A, et al. Practice guideline for the treatment ofcoccidioidomycosis. Infectious Diseases Society of America. Clin Infect Dis 2000; 30:658.

57. Sondermeyer GL, Lee LA, Gilliss D, et al. Epidemiology of Pediatric Coccidioidomycosis inCalifornia, 2000-2012. Pediatr Infect Dis J 2016; 35:166.


































58. Ho AK, Shrader MW, Falk MN, Segal LS. Diagnosis and initial management of musculoskeletalcoccidioidomycosis in children. J Pediatr Orthop 2014; 34:571.

59. Bisla RS, Taber TH Jr. Coccidioidomycosis of bone and joints. Clin Orthop Relat Res 1976; :196.

60. Corrall CJ, Merz WG, Rekedal K, Hughes WT. Aspergillus osteomyelitis in an immunocompetentadolescent: a case report and review of the literature. Pediatrics 1982; 70:455.

61. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease. Report on anational registry of 368 patients. Medicine (Baltimore) 2000; 79:155.

62. Nelson JD. Acute osteomyelitis in children. Infect Dis Clin North Am 1990; 4:513.

63. Gill FM, Sleeper LA, Weiner SJ, et al. Clinical events in the first decade in a cohort of infants withsickle cell disease. Cooperative Study of Sickle Cell Disease. Blood 1995; 86:776.

64. Bennett OM. Salmonella osteomyelitis and the hand-foot syndrome in sickle cell disease. J PediatrOrthop 1992; 12:534.

65. Webb DK, Serjeant GR. Haemophilus influenzae osteomyelitis complicating dactylitis inhomozygous sickle cell disease. Eur J Pediatr 1990; 149:613.

66. Chambers JB, Forsythe DA, Bertrand SL, et al. Retrospective review of osteoarticular infections ina pediatric sickle cell age group. J Pediatr Orthop 2000; 20:682.

67. Burnett MW, Bass JW, Cook BA. Etiology of osteomyelitis complicating sickle cell disease.Pediatrics 1998; 101:296.

68. HOOK EW, CAMPBELL CG, WEENS HS, COOPER GR. Salmonella osteomyelitis in patients withsickle-cell anemia. N Engl J Med 1957; 257:403.

69. Syrogiannopoulos GA, McCracken GH Jr, Nelson JD. Osteoarticular infections in children withsickle cell disease. Pediatrics 1986; 78:1090.

70. Sadat-Ali M. The status of acute osteomyelitis in sickle cell disease. A 15-year review. Int Surg1998; 83:84.

71. Robertson AJ, Firth GB, Truda C, et al. Epidemiology of acute osteoarticular sepsis in a setting witha high prevalence of pediatric HIV infection. J Pediatr Orthop 2012; 32:215.






























GRAPHICS

Pathogenesis of acute osteomyelitis in children

(A) During an episode of bacteremia, bacteria are deposited in the metaphysisfrom the metaphyseal vessels (nutrient artery and vein).(B) A focus of infection develops in the metaphysis, which leads to cellulitis in thebone marrow.(C) Exudate under pressure is forced laterally through the Haversian systems andVolkmann canals and into the cortex of the bone, where it can lift or rupturethrough the periosteum.




Brodie abscess radiograph

Lateral (A) and frontal (B) radiographs of the right lower extremity demonstrate an ovoid lucentlesion in the medullary cavity of the proximal metadiaphysis of the tibia (arrows) withassociated periosteal reaction (arrowheads). The lateral radiograph (A) also demonstratesirregular cortical lucency anteriorly suggesting an area of focal cortical disruption (dashedarrow).

Reproduced with permission from: Abdulhadi MA, White AM, Pollock AN. Brodie abscess. Pediatr EmergCare 2012; 28:1249. Copyright © 2012 Lippincott Williams & Wilkins.




Developmental pathogenesis of acute osteomyelitis

(A) In newborns, infection commonly spreads along the subperiosteal space andruptures through the cortex into soft tissue or adjacent joint spaces.(B and C) In infants and older children, capillaries do not cross the physis.Infection in older children is generally confined to the metaphysis, and thethicker cortex and denser periosteum limit spread to soft tissues.




Clinical features associated with bacterial pathogens that cause acute hematogenousosteomyelitis in children

Clinical features

Gram-positive bacteria

Staphylococcus aureus All ages; possible associated skin or soft tissue infection; MRSA may be associatedwith venous thromboembolism and pulmonary disease

Coagulase-negativestaphylococci

Neonates in intensive care unit; children with indwelling vascular catheters (eg, forchronic hemodialysis)

Group A Streptococcus More common in children younger than 4 years; may occur as a complication ofconcurrent varicella-zoster virus infection

Group B Streptococcus Infants younger than 3 months (usually 2 to 4 weeks)

Streptococcus pneumoniae Children younger than 2 years who are incompletely immunized; children older than2 years with underlying medical conditions (eg, sickle cell disease, asplenia, splenicdysfunction, immunodeficiency, chronic heart disease, chronic lung disease, diabetesmellitus)

Actinomyces May affect the facial bones, the pelvis, or vertebral bodies

Gram-negative bacteria

Kingella kingae Children 6 to 36 months; indolent onset; oral ulcers preceding musculoskeletalfindings; may affect nontubular bones

Nonsalmonella gram-negativebacilli (eg, Escherichia coli,Serratia)

Birth to 3 months; children with sickle cell disease; instrumentation of thegastrointestinal or urinary tract; immunocompromised host (eg, CGD)

Haemophilus influenzae type b Incompletely immunized children in areas with low Hib immunization rates

Bartonella henselae Children with cat exposure; may affect the vertebral column and pelvic girdle; maycause multifocal infection

Pseudomonas aeruginosa Injectable drug use

Brucella Travel to or living in an endemic area; ingestion of unpasteurized dairy products

Mycobacterium tuberculosis Birth in, travel to, or contact with a visitor from, a region endemic for M. tuberculosis

Nontuberculous mycobacteria Surgery or penetrating injury; CGD; other underlying immunodeficiency; HIVinfection

Salmonella species Children with sickle cell disease or related hemoglobinopathies; exposure to reptilesor amphibians; children with gastrointestinal symptoms; children in developingcountries

Polymicrobial infection More likely with direct inoculation (eg, penetrating trauma) or contiguous spread (eg,from skull, face, hands, feet)

MRSA: methicillin-resistant S. aureus; CGD: chronic granulomatous disease; Hib: H. influenzae type b.



Paul Krogstad, MD Nothing to disclose Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: Pfizer[Streptococcus pneumoniae]; Merck [Staphylococcus aureus]; MeMed Diagnostics [Bacterial and viral infections].Consultant/Advisory Board: Pfizer [Staphylococcus aureus]. Other Financial Interest: Pfizer [Speaker on PCV13,linezolid]; Medscape [Video discussion on bacterial meningitis]; Elsevier [Co-editor (Feigin and Cherry Textbook ofPediatric Infectious Diseases)]. William A Phillips, MD Nothing to disclose Mary M Torchia, MD Nothing to disclose


Hematogenous osteomyelitis in children: Evaluation and diagnosis - UpToDate



Hematogenous osteomyelitis in children: Evaluation anddiagnosisAuthor: Paul Krogstad, MD Section Editors: Sheldon L Kaplan, MD, William A Phillips, MD Deputy Editor: Mary M Torchia,MD



INTRODUCTION

The evaluation and diagnosis of hematogenous osteomyelitis in children will be discussed here. Theepidemiology, pathogenesis, microbiology, clinical features, complications, and management ofosteomyelitis in children osteomyelitis are discussed separately:

DEFINITION AND PATHOGENESIS

Osteomyelitis is an infection localized to bone. It is usually caused by microorganisms (predominantlybacteria) that enter the bone hematogenously.

Osteomyelitis also may result from direct inoculation of bone with bacteria in association with an openfracture or as a complication of puncture wounds or the placement of orthopedic hardware (such as pinsor screws). (See "Infectious complications of puncture wounds".)

Less commonly, osteomyelitis may arise as an extension of a contiguous infection (eg, decubitus ulcer,sinusitis, periodontal disease).

DIAGNOSTIC APPROACH

Overview — The diagnosis of osteomyelitis is supported by a combination of [1]:

®

(See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology".)●



Clinical features suggestive of bone infection (constitutional symptoms, focal symptoms and signs of●

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References

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https://www.uptodate.com/contents/hematogenous-osteomyelitis-in-children-evaluation-and-diagnosis/abstract/1






The diagnosis often is unclear at the initial evaluation. The initial presentation may be delayed, and signsand symptoms nonspecific. A high index of suspicion and monitoring of the clinical course are essentialto establishing the diagnosis. We suggest that an orthopedic surgeon or interventional radiologist beconsulted as early as possible to assist in obtaining specimens from the site of infection and assessingthe need for surgical intervention. (See 'Microbiology' below and "Hematogenous osteomyelitis inchildren: Management", section on 'Indications for surgery'.)

The diagnosis is confirmed by histopathologic evidence of inflammation in a surgical specimen of bone(picture 1A-C) (if obtained) or identification of a pathogen by culture or Gram stain in an aspirate orbiopsy of bone [2].

The diagnosis is probable in a child with compatible clinical, laboratory, and/or radiologic findings (table1) in whom a pathogen is isolated from blood, periosteal collection, or joint fluid. We also consider thediagnosis to be probable in a child with compatible clinical, laboratory, and radiologic findings andnegative cultures if he or she responds as expected to empiric antimicrobial therapy.

The diagnosis is unlikely if advanced imaging studies (particularly magnetic resonance imaging [MRI])are normal.

Clinical suspicion — Based upon the history and physical examination, acute hematogenousosteomyelitis should be suspected in infants and children with findings suggestive of bone infection,including:

Additional clinical features of osteomyelitis in children are discussed separately. (See "Hematogenousosteomyelitis in children: Clinical features and complications", section on 'Clinical features'.)

Osteomyelitis also should also be considered in children who are found to have bacteremia or an

bone inflammation, limitation of function, elevated erythrocyte sedimentation rate [ESR], and/or C-reactive protein [CRP]) (see 'Clinical suspicion' below and 'Blood tests' below)

An imaging study with abnormalities characteristic of osteomyelitis (table 1) (see 'Plain radiographs'below and 'Advanced imaging' below)

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A positive microbiologic or histopathologic specimen (see 'Microbiology' below and 'Histopathology'below)

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A response to empiric antimicrobial therapy (see 'Response to empiric therapy' below)●

Constitutional symptoms (irritability, decreased appetite or activity), with or without fever●

Focal symptoms and signs of bone inflammation (eg, warmth, swelling, point tenderness) thattypically progress over several days to a week; symptoms and signs in infants and small childrenmay be poorly localized

●

Limitation of function (limited use of an extremity; limp; refusal to walk, crawl, sit, or bear weight)●

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abnormal imaging study of bone in the evaluation of trauma or nonspecific signs or symptoms (eg,irritability, fever without a source).

Risk factors that may raise suspicion for osteomyelitis include (see "Hematogenous osteomyelitis inchildren: Epidemiology, pathogenesis, and microbiology", section on 'Risk factors'):

Initial evaluation — The initial evaluation for children with suspected osteomyelitis includes blood testsand plain radiographs of the affected area(s).

Blood tests — Initial blood tests for children with suspected osteomyelitis include a complete bloodcount (CBC) with differential, ESR, and/or CRP [3]. To avoid multiple venipunctures, at least one bloodculture should be obtained at the same time as these studies. Blood cultures are discussed below. (See'Microbiology' below.)

At the time of presentation, elevation of ESR (>20 mm/h) and/or CRP (>10 to 20 mg/L [1 to 2 mg/dL]) issensitive (approximately 95 percent) in cases of culture-proven osteomyelitis in children, but ESR andCRP are nonspecific [4-6]. Elevated ESR and/or CRP support the diagnosis of osteomyelitis but do notexclude other conditions in the differential diagnosis. ESR and CRP may be normal early in the infectionin some patients, and repeat testing may be warranted within 24 hours in children in whom osteomyelitisis strongly suspected. ESR and CRP also are important markers for evaluating the response to therapy.(See "Hematogenous osteomyelitis in children: Management", section on 'Response to therapy'.)

Elevation of the white blood cell (WBC) count is variable and nonspecific [7]. In a 2012 systematic reviewof >12,000 patients, the WBC was elevated in only 36 percent [5]. However, the CBC and differential arehelpful in evaluating other considerations in the differential diagnosis of children with bone pain (eg, vaso-occlusive crisis in sickle cell disease, leukemia). (See 'Differential diagnosis' below.)

Plain radiographs — Plain radiograph(s) of the affected region(s) should be performed as the initialimaging study to exclude other causes of pain (eg, bone tumors and fractures) [3,8,9]. Plain radiographsare usually normal or inconclusive early in the course of osteomyelitis, often necessitating advancedimaging when osteomyelitis is suspected. Newborn infants are an exception to this general rule; plainradiographs are abnormal at the time of evaluation in most newborn and young infants who are ultimatelyfound to have osteomyelitis [10,11]. (See 'Advanced imaging' below and 'Differential diagnosis' below.)

Characteristic findings — Children with suspected osteomyelitis and characteristic abnormalitieson initial plain radiographs are likely to have osteomyelitis (table 1). They should receive empiricantibiotic therapy pending further evaluation (microbiology and possibly additional imaging studies). (See

Bacteremia or sepsis●

Immune deficiency (eg, sickle cell disease, chronic granulomatous disease)●

Indwelling vascular catheter, including hemodialysis catheter●

For neonates – Prematurity, skin infection, complicated delivery, urinary tract anomalies, late onsetneonatal sepsis

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"Hematogenous osteomyelitis in children: Management", section on 'Empiric parenteral therapy' and'Microbiology' below and 'Advanced imaging' below.)

Plain radiographic findings that are compatible with osteomyelitis include:

However, these findings generally are not apparent at the onset of symptoms. The timing and typicalsequence of radiographic changes of osteomyelitis varies depending on which bones are affected andthe age of the patient.

Evidence of periosteal new bone formation (periosteal reaction) (image 1A-B)●

Periosteal elevation (suggestive of periosteal abscess) (image 1D)●

Lytic lesions (image 1C) or sclerosis, indicating subacute/chronic infection●

Long bones – The typical sequence of radiographic changes in long bones of children is as follows[12,13]:

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Approximately three days after symptom onset – Small area of localized, deep, soft-tissueswelling in the region of the metaphysis (image 2)

•

Three to seven days after symptom onset – Obliteration of the translucent fat planes interposedwithin muscle by edema fluid

•

Ten to 21 days after symptom onset (7 to 10 days in neonates) – Evidence of bone destruction(osteopenia, osteolytic lesions), periosteal reaction, cortical thickening, periosteal elevation (dueto subcortical purulence (image 1A-D)); these lesions may require surgical debridement ordrainage (see "Hematogenous osteomyelitis in children: Management", section on 'Indicationsfor surgery')

•

One month or longer – Lytic sclerosis•

Membranous, irregular bones – Bone destruction and periosteal elevation generally are apparenttwo to three weeks later than in long bones.

●

Pelvic bones – Plain radiographs usually are not useful in the diagnostic evaluation of osteomyelitisof the pelvis; they were abnormal in only 25 percent of patients in one large series [14].

●

Vertebral osteomyelitis – In children with vertebral osteomyelitis, plain films may be normal at initialpresentation in more than 50 percent of cases [15]. Initial abnormalities may include localizedrarefaction of one vertebral plateau, followed by involvement of adjacent vertebrae. Markeddestruction of bone, usually anteriorly, can occur, followed by anterior osteophytic reactions withbridging and bone sclerosis.

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Discitis – The radiographic changes of discitis are first noted several weeks after the onset ofsymptoms, with the following sequence:

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Narrowing of the disc space two to four weeks after the onset of symptoms•

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Normal plain radiographs — A normal plain radiograph early in the course (eg, within seven daysof symptom onset) does not exclude osteomyelitis. Children with suspected osteomyelitis (eg, localizedbone pain, limited function, elevated ESR or CRP) and normal initial plain radiographs generally shouldreceive empiric antibiotic therapy pending additional imaging and the results of microbiologic studies.However, school-age children who are afebrile and have equivocal physical examination findings, andnormal plain radiographs may occasionally be followed closely without antimicrobial therapy pendingadditional evaluation. (See "Hematogenous osteomyelitis in children: Management", section on 'Empiricparenteral therapy' and 'Advanced imaging' below and 'Microbiology' below.)

Further imaging, usually with MRI or scintigraphy, should be performed as soon as possible in any childwith suspected osteomyelitis whose initial radiographs are normal, regardless of whether antibiotictherapy is initiated (image 3). (See 'Advanced imaging' below.)

Advanced imaging — Most children with suspected osteomyelitis undergo additional imaging with MRI,scintigraphy, computed tomography (CT), and/or ultrasonography (table 2). Indications for additionalimaging studies may include:

Magnetic resonance imaging — If it is available, MRI is the imaging modality of choice whenimaging other than plain radiography is needed to establish the diagnosis of osteomyelitis (eg, early inthe course) or to delineate the location and extent of bone and soft tissue involvement (table 2) [3,8,9].Intravenous contrast is not generally required but may help define intramedullary abscess orintramuscular abscesses [16]. Osteomyelitis is unlikely if MRI is negative.

MRI is particularly useful in identifying and/or distinguishing:

Destruction of the adjacent cartilaginous vertebral end-plates•

Herniation of the disc into the vertebral body•

In older children, anterior spontaneous fusion is common. Rarely, vertebral body compression orwedging is noted.

Despite the delay in radiographic changes, findings suggestive of discitis often are apparent at thetime of presentation (because of the indolent course). In one series, as an example, radiographicchanges were present on initial evaluation in more than 70 percent of cases [15].

Confirmation of the diagnosis in children with normal initial plain radiographs●

Further evaluation of abnormalities identified on plain radiographs (eg, bone destruction)●

Evaluation of extension of infection (eg, growth plate, epiphysis, joint, adjacent soft tissues)●

Guidance for percutaneous diagnostic and therapeutic drainage procedures (eg, needle aspiration,abscess drainage)

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Early changes in the bone marrow cavity (before changes in cortical bone are apparent on plainradiographs) [17]

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The major advantages of MRI compared with other imaging modalities include accurate identification ofsubperiosteal or soft-tissue collections of pus and avoidance of exposure to ionizing radiation [24]. Inaddition, the efficacy of MRI does not appear to be affected by diagnostic or surgical intervention.

Disadvantages of MRI include a longer scanning time than CT and the need for sedation or generalanesthesia for an adequate study in most young children, which may be a limiting factor in someinstitutions. MRI is less useful when multiple sites of involvement are suspected or there are no localizedclinical findings. Finally, MRI is not always readily available.

MRI demonstrates excellent anatomic detail and differentiation among soft tissue, bone marrow, andbone (image 5).

MRI abnormalities in discitis include reduction of disc space, increased T2 signal in the adjacent vertebral

Pelvic osteomyelitis [18-20]●

Involvement of the vertebral body and the adjacent disc in children with vertebral osteomyelitis●

Areas that may require surgical drainage (eg, sinus tracts, intraosseous abscesses, subperiosteal orsoft-tissue collections of pus) (image 4) (see "Hematogenous osteomyelitis in children:Management", section on 'Indications for surgery')

●

Involvement of the growth plate (image 3) [21-23]●

Contiguous septic arthritis (especially in the evaluation of young children with possible septic arthritisof the hip or femoral osteomyelitis)

●

Associated pyomyositis●

Evidence of venous thrombosis●

Areas of active inflammation show a decreased signal in T1-weighted images and an increasedsignal in T2-weighted images [25]. Fat-suppression sequences, including short-tau inversionrecovery (STIR), decrease the signal from fat and are more sensitive for the detection of bone-marrow edema.

●

The penumbra sign (high-intensity-signal transition zone between abscess and sclerotic bonemarrow in T1-weighted images (image 6)) is characteristic of subacute osteomyelitis and in onestudy was helpful in differentiating between indolent infections and neoplasms [26].

●

The signal from infected bone marrow can be enhanced with intravenous gadolinium contrast [27],but this is seldom necessary for diagnostic purposes [16,28]. Because of the risk of nephrogenicsystemic fibrosis, imaging with gadolinium should be avoided, if possible, in patients with moderateor advanced renal failure. (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy inadvanced kidney disease".)

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end plates, and signal intensity changes in the intervening discs [15,17].

The sensitivity and specificity for the detection of bone involvement in children with suspectedosteomyelitis with MRI are high (80 to 100 percent and 70 to 100 percent, respectively, in a 2012systematic review) [5]. Given the high sensitivity, osteomyelitis is unlikely if the MRI is negative [8]. False-positive results may occur in patients with adjacent soft tissue infection; adjacent soft tissue infection cancause edema of the bone that may be interpreted as "consistent with osteomyelitis" but representssympathetic inflammation rather than bone infection.

Scintigraphy — We suggest scintigraphy (also known as radionuclide scanning or bone scan) whenMRI is not available and imaging other than plain radiography is needed to establish the diagnosis ofosteomyelitis (table 2). Scintigraphy also may be useful when the area of suspected infection cannot belocalized or multiple areas of involvement are suspected.

Scintigraphy is helpful early in the course, readily available, relatively inexpensive, and requires sedationless frequently than MRI in young children. However, it does not provide information about the extent ofpurulent collections that may require drainage (eg, intramedullary abscess, muscular phlegmon) [8].Scintigraphy may be falsely negative if the blood supply to the periosteum is disrupted (eg, subperiostealabscess) and during the transition between decreased and increased activity [29,30]. In addition,scintigraphy involves exposure to ionizing radiation [31].

The three-phase bone scan utilizing technetium 99m (99mTc) usually is performed as the initial nuclearmedicine procedure in the evaluation of osteomyelitis. It consists of:

Increased uptake of tracer in the first two phases can be caused by anything that increases blood flowand is accompanied by inflammation. Osteomyelitis causes focal uptake in the third phase; the intensityof the signal reflects the level of osteoblastic activity. Localization of a lesion near a growth plate cancomplicate interpretation.

The sensitivity and specificity for the detection of bone involvement in children with suspectedosteomyelitis with scintigraphy generally are high, but the range is wider than MRI (53 to 100 percent and50 to 100 percent, respectively in a 2012 systematic review) [5]. Sensitivity is variable in neonates butappears to be lower than in older children [10,32,33]. Scintigraphy has been shown to have poorsensitivity (53 percent) in cases of osteomyelitis caused by methicillin-resistant Staphylococcus aureus(MRSA) [8].

MRI generally is preferred if the results of the three-phase 99mTc bone scan are equivocal. Scintigraphywith inflammation imaging tracers (eg, gallium or indium) may be helpful but involve additional exposureto radiation.

A nuclear angiogram (the flow phase), obtained two to five seconds after injection●

The blood pool phase, obtained 5 to 10 minutes after injection●

The delayed phase, specific for bone uptake, obtained two to four hours after injection●













Computed tomography — MRI usually is preferred to CT in the evaluation of suspectedosteomyelitis. However, CT better delineates changes in bone and may be preferred when significantbone destruction is identified on plain radiographs [17]. CT findings of osteomyelitis include increaseddensity of bone marrow, periosteal new bone formation, and periosteal purulence.

Other potential indications for CT may include:

CT is less time consuming than MRI, and young children usually do not require sedation. However, CTexposes children to ionizing radiation.

Ultrasonography — Ultrasonography usually is not helpful in the diagnosis of osteomyelitis. However,it can identify fluid collections associated with bone infections and may improve the success ofpercutaneous diagnostic and therapeutic drainage procedures [9,34].

Ultrasonography findings consistent with osteomyelitis include fluid collection adjacent to the bonewithout intervening soft tissue, elevation of the periosteum by more than 2 mm, and thickening of theperiosteum. (See "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis",section on 'Ultrasonography'.)

Microbiology

General principles — Isolation of a pathogen from bone, subperiosteal fluid collection, joint fluid, orblood establishes a diagnosis of confirmed or probable osteomyelitis in children with compatible clinicaland/or radiologic findings and speciation and susceptibility testing are essential for planning treatment.(See "Hematogenous osteomyelitis in children: Management", section on 'Antimicrobial therapy'.)

With an increasing proportion of cases caused by antibiotic-resistant organisms (eg, community-associated MRSA) and previously unusual species (eg, Kingella kingae in young children), it isparticularly important to collect specimens for culture from as many sites of infection as possible.

It is preferable to obtain microbiologic specimens before administration of antibiotics, but this must beweighed against the potential for additional complications of ongoing bacteremia by S. aureus or otherpathogens. If bone culture cannot be obtained immediately, decisions regarding immediate or delayedadministration of antibiotics generally are made in consultation with the orthopedic surgeon. For childrenwith signs of systemic illness (eg, fever, tachycardia), we provide antibiotic therapy immediately followingblood culture. In a retrospective review of 250 cases of osteomyelitis, the rates of culture positivity weresimilar (approximately 74 percent) whether or not patients received antibiotics before cultures wereobtained, although there was a tendency for cultures obtained by interventional radiology to more likelybe positive if obtained within 24 hours of initiating antibiotic treatment [35]. In another retrospective study,

Delineation of the extent of bone injury in chronic osteomyelitis or planning the surgical approach todebridement of devitalized bone (sequestra)

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Lack of availability of MRI or contraindications to MRI●



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operative cultures were positive in 42 of 50 children (84 percent) with osteomyelitis who receivedpreoperative antibiotics [36].

Sites to culture — Specimens for culture should be obtained from blood and as many potential sitesof infection as possible. An orthopedic surgeon and/or interventional radiologist should be consulted asearly as possible in the evaluation of children with suspected osteomyelitis to assist in obtainingspecimens for histopathology and/or culture and assessing the need for surgical intervention. In aretrospective review of 250 cases of osteomyelitis from a single institution, blood cultures were positive in46 percent of cases in which they were obtained, cultures obtained in the operating room (OR, bone,subperiosteal abscess, adjacent septic arthritis) were positive in 82 percent, and cultures obtained ininterventional radiology (IR) were positive in 52 percent [35]. OR/IR cultures were positive in 80 patientswho had negative blood cultures; among these cases, results of OR/IR cultures prompted a change inantibiotic therapy in 68 (85 percent).

It is important to let the microbiology lab know if less common or fastidious organisms (eg, K. kingae) aresuspected because they may require specific media, growth conditions, or prolonged culture time (table3) [37].

Blood cultures – We recommend at least one, and preferably two, blood cultures be obtained beforeadministration of antibiotics to children with osteomyelitis. Although less frequently positive thancultures from bone or adjacent abscesses, blood cultures may be the only positive source ofidentification of the pathogen [5,35,37,38].

●

Bone culture – Bone samples for culture, Gram stain, and histopathology should be obtainedwhenever possible [35,38]. Culture specimens may be obtained by percutaneous needle aspiration(which may be guided by ultrasonography, fluoroscopy, or other imaging modality) or open biopsy(particularly if surgery is required for therapeutic drainage and debridement). (See "Hematogenousosteomyelitis in children: Management", section on 'Indications for surgery'.)

●

Other cultures – Subperiosteal exudate, joint fluid, and pus from adjoining sites of infection should beobtained and sent for Gram stain and culture whenever possible, as directed by imaging studies [35].Specimens may be obtained by percutaneous needle aspiration (which may be guided byultrasonography, fluoroscopy, or other imaging modality). Injection of bone aspirates or periostealcollections into blood culture bottles is recommended to enhance recovery of K. kingae [39,40]. (See"Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", sectionon 'Kingella kingae'.)

●

Percutaneous needle aspiration is often successful in neonates with extensive soft-tissue andperiosteal involvement and infants and young children with subperiosteal collections.

Percutaneous techniques are less successful in older children and adolescents, who may requirebone aspiration or drilling to obtain culture specimens. In such cases, the risk of epiphyseal damageand further destruction of bone must be weighed against the benefit of obtaining a specimen.






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As reported in a 2012 systematic review of observational studies of osteomyelitis (during or after 2000), apathogen is isolated from any culture (blood, tissue, pus) in approximately 50 percent of cases [5]. Theyield of cultures of bone tissue or pus is greater than that from blood cultures (70 versus 40 percent).

Other microbiologic studies — Other microbiologic studies may be helpful in the detection ofspecific pathogens. Polymerase chain reaction (if available) can be particularly helpful for detecting K.kingae in purulent materials or bone specimens [41-43].

Histopathology — The diagnosis of osteomyelitis is confirmed in children who have histopathologicevidence of inflammation in a surgical specimen of bone (picture 1A-C). An orthopedic surgeon and/orinterventional radiologist should be consulted as early as possible in the evaluation of children withsuspected osteomyelitis to assist in obtaining specimens for histopathology and/or culture and assessingthe need for surgical intervention.

Histopathologic specimens may be obtained by percutaneous needle aspiration (which may be guided byultrasonography, fluoroscopy, or other imaging modality) or open biopsy (particularly if surgery is requiredfor therapeutic drainage and debridement). (See "Hematogenous osteomyelitis in children:Management", section on 'Indications for surgery'.)

Response to empiric therapy — Improvement in constitutional symptoms and localized inflammation(eg, erythema, point tenderness) with empiric antimicrobial therapy helps to support the diagnosis ofosteomyelitis, particularly in children in whom no pathogen is isolated. (See "Hematogenousosteomyelitis in children: Management", section on 'Response to therapy' and 'Probable osteomyelitis'below.)

In children with normal MRI and/or scintigraphy, a lack of clinical response to empiric therapy and theresults of blood cultures help to direct additional evaluation for other conditions in the differentialdiagnosis. (See 'Osteomyelitis unlikely (advanced imaging studies normal)' below and 'Differentialdiagnosis' below.)

DIAGNOSTIC INTERPRETATION

Confirmed osteomyelitis — The diagnosis of osteomyelitis is confirmed by histopathologic evidence ofinflammation in a surgical specimen of bone (picture 1A-C) (if obtained) or identification of a pathogen byculture or Gram stain in an aspirate of bone [2].

Probable osteomyelitis — The diagnosis of osteomyelitis is probable in a child with compatible clinical,laboratory, and/or radiologic findings (table 2) in whom a pathogen is isolated from blood, periostealcollection, or joint fluid. We also consider the diagnosis to be probable in a child with compatible clinical,laboratory, and radiologic findings and negative cultures if he or she responds as expected to empiricantimicrobial therapy.













Given the potential morbidity of delayed treatment, children with probable osteomyelitis should bemanaged in the same manner as children in whom infection has been confirmed by isolation of anorganism from bone or blood [44]. (See "Hematogenous osteomyelitis in children: Clinical features andcomplications", section on 'Complications' and "Hematogenous osteomyelitis in children: Management",section on 'Empiric parenteral therapy'.)

The response to empiric antimicrobial therapy in children with culture-negative osteomyelitis directs theneed for additional evaluation. (See "Hematogenous osteomyelitis in children: Management", section on'Culture-negative osteomyelitis'.)

Osteomyelitis unlikely (advanced imaging studies normal) — Osteomyelitis is unlikely if advancedimaging studies (usually magnetic resonance imaging or scintigraphy) are normal. The majorconsiderations in the differential diagnosis and approach to continued evaluation and managementdepend upon the results of the blood culture and response to antimicrobial therapy:

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of osteomyelitis includes infectious conditions, noninfectious conditions, andradiographic mimics (table 4).

Other infections — Infections that do not involve bone may cause fever, pain, and tenderness overlyingbone, mimicking hematogenous osteomyelitis. These infections usually are distinguished fromosteomyelitis by imaging studies that lack the characteristic features of osteomyelitis (table 1). (See'Advanced imaging' above.)

Other infections that may share features of osteomyelitis (and may complicate or be complicated byosteomyelitis) include:

Positive blood culture, improvement with empiric therapy – A source of infection other thanosteomyelitis must be sought (see 'Other infections' below)

●

Positive blood culture, no improvement with appropriate therapy – Other sources of bacteremia andnoninfectious conditions that may have predisposed the patient to bacteremia must be soughtaggressively (see 'Differential diagnosis' below)

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Negative blood culture, improvement with empiric therapy – The child may have a more superficialsource of infection (eg, cellulitis); a shorter course of antimicrobial therapy may be warranted (see'Other infections' below)

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Negative blood culture, no improvement with appropriate therapy – A bacterial infection is unlikely;fungal and noninfectious causes of musculoskeletal pain should be sought; discontinuation ofempiric antimicrobial therapy may be warranted (see 'Noninfectious conditions' below)

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Septicemia (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm●


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Noninfectious conditions

Chronic nonbacterial osteomyelitis — Chronic nonbacterial osteomyelitis (CNO; also called chronicrecurrent multifocal osteomyelitis [CRMO]) is a chronic inflammatory bone disorder that primarily affectschildren. It is characterized by bone pain with insidious onset. The initial presentation is similar to that ofosteomyelitis. Imaging may localize the areas of bony involvement and indicate the absence of featuressuggestive of chronic osteomyelitis, such as an abscess or sinus tract. However, microbiologic andpathologic studies from bone biopsy specimens are generally necessary to differentiate CNO fromosteomyelitis. The evaluation and treatment of CNO are discussed in detail separately. (See "Chronicnonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO)".)

Other noninfectious conditions — Several noninfectious conditions have clinical features thatoverlap with osteomyelitis. These include:

infants", section on 'Clinical manifestations' and "Systemic inflammatory response syndrome (SIRS)and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on'Clinical manifestations')

Cellulitis (see "Cellulitis and skin abscess: Clinical manifestations and diagnosis", section on'Cellulitis and erysipelas')

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Septic arthritis; approximately one-third of cases of osteomyelitis extend to the contiguous joint (asmany as 75 percent in neonates) [45-48] (see "Bacterial arthritis: Clinical features and diagnosis ininfants and children", section on 'Clinical features')

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Deep abscesses (eg, psoas abscess) (see "Psoas abscess", section on 'Clinical manifestations')●

Pyomyositis (see "Pyomyositis", section on 'Clinical manifestations')●

Malignancy – Tumor growth can cause bone pain, and some children with malignancies (particularlyleukemia and Ewing sarcoma) have fever as part of their initial presentation. Unlike those withosteomyelitis, symptoms can be intermittent in children with cancer. Affected children also fail torespond to empiric antibiotic therapy. Osteomyelitis and cancer involving bone are usuallydifferentiated with bone biopsy. (See "Clinical assessment of the child with suspected cancer",section on 'Bone and joint pain' and "Overview of the clinical presentation and diagnosis of acutelymphoblastic leukemia/lymphoma in children" and "Clinical presentation, staging, and prognosticfactors of the Ewing sarcoma family of tumors", section on 'Signs and symptoms' and "Bone tumors:Diagnosis and biopsy techniques".)

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Bone infarction – Bone infarction secondary to hemoglobinopathy, especially in infants withdactylitis, can be particularly difficult to distinguish from osteomyelitis.

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Plain radiographs, scintigraphy, and MRI all show similar results in both conditions. Unlike bonedisease with hemoglobinopathy, osteomyelitis does not respond to hydration and other supportive

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https://www.uptodate.com/contents/bone-tumors-diagnosis-and-biopsy-techniques?search=osteomyelitis&topicRef=6067&source=see_link




Radiographic mimics — Benign and malignant bone tumors and tumors involving bone can haveradiographic appearance similar to osteomyelitis. The acute clinical features and response to antibioticsin children with osteomyelitis usually distinguish osteomyelitis from these conditions. However, bonebiopsy can be performed if necessary for histopathologic differentiation.

Bone lesions that can have radiographic appearance similar to osteomyelitis include (table 4):

measures. (See "Acute and chronic bone complications of sickle cell disease".)

Vitamin C deficiency – Vitamin C deficiency (scurvy) may cause musculoskeletal pain and refusalto bear weight, particularly in children with autism spectrum disorder, intellectual disability, foodaversion, or limited food preferences [49]. Additional findings of vitamin C deficiency may includepetechiae, ecchymoses, bleeding gums, coiled hairs, and hyperkeratosis (picture 2). (See "Overviewof water-soluble vitamins", section on 'Deficiency'.)

●

Gaucher disease – Children with Gaucher disease can have painful bone crises similar to thosethat occur in patients with sickle cell disease. During bone pain crises, ischemia can be detected bytechnetium bone scan. Radiographs of the distal femur may demonstrate deformities caused byabnormal modeling of the metaphysis that are characteristic of Gaucher disease. However, thepossibility of osteomyelitis should be considered in febrile patients with Gaucher disease who do notimprove with hydration and other supportive measures. (See "Gaucher disease: Pathogenesis,clinical manifestations, and diagnosis" and "Gaucher disease: Treatment", section on 'Skeletaldisease'.)

●

Complex regional pain syndrome – Complex regional pain syndrome (CRPS) is an uncommonchronic condition that causes pain, swelling, and limited range of motion in the affected extremity. Itfrequently begins after an injury, surgery, or vascular event. Vasomotor instability and chronic skinchanges also occur. CRPS may be distinguished from osteomyelitis by autonomic dysfunction andnormal ESR/CRP. (See "Complex regional pain syndrome in children", section on 'Diagnosis'.)

●

Caffey disease – Caffey disease (infantile cortical hyperostosis) is an inherited diseasecharacterized by fever, subperiosteal bone hyperplasia, and swelling of overlying soft tissues. It is arare disorder and is difficult to distinguish from osteomyelitis on initial presentation. The disorderscan be distinguished on bone biopsy. (See "Differential diagnosis of the orthopedic manifestations ofchild abuse", section on 'Infantile cortical hyperostosis (Caffey disease)'.)

●

Fibrous dysplasia (see "Nonmalignant bone lesions in children and adolescents", section on 'Fibrousdysplasia')

●

Osteoid osteoma and osteoblastoma (see "Nonmalignant bone lesions in children and adolescents",section on 'Bone-forming lesions')

●

Chondroblastoma and chondromyxoid fibroma (see "Nonmalignant bone lesions in children andadolescents", section on 'Cartilage-forming tumors')

●




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SUMMARY AND RECOMMENDATIONS

Eosinophilic granuloma and other forms of histiocytosis (see "Langerhans cell histiocytosis(eosinophilic granuloma) of bone in children and adolescents")

●

Osteosarcoma (see "Osteosarcoma: Epidemiology, pathogenesis, clinical presentation, diagnosis,and histology", section on 'Clinical presentation')

●

The diagnosis of osteomyelitis is supported by a combination of clinical features suggestive of boneinfection, an imaging study with abnormalities characteristic of osteomyelitis (table 1), a positivemicrobiologic or histopathologic specimen, and/or a response to empiric antimicrobial therapy.

●

The diagnosis often is unclear at the initial evaluation. A high index of suspicion and monitoring ofthe clinical course are essential to establishing the diagnosis. An orthopedic surgeon and/orinterventional radiologist should be consulted as early as possible in the evaluation to assist inobtaining specimens for culture and/or histopathology. (See 'Overview' above.)

Acute hematogenous osteomyelitis should be suspected in infants and children with findingssuggestive of bone infection, including:

●

Constitutional symptoms (irritability, decreased appetite or activity), with or without fever•

Focal findings of bone inflammation (eg, warmth, swelling, point tenderness) that typicallyprogress over several days to a week

•

Limitation of function (eg, limited use of an extremity; limp; refusal to walk, crawl, sit, or bearweight)

•

Osteomyelitis should also be suspected in children who are found to have bacteremia or an imagingstudy with characteristic findings during the evaluation of other conditions (eg, fever, trauma). (See'Clinical suspicion' above.)

The initial evaluation of children with suspected osteomyelitis includes complete blood count withdifferential, erythrocyte sedimentation rate, C-reactive protein, blood culture, and plain radiographs.(See 'Initial evaluation' above.)

●

Plain radiographs may be sufficient to confirm a diagnosis of osteomyelitis. If needed, additional●



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REFERENCES

1. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch DisChild 2012; 97:545.

2. Krogstad P. Osteomyelitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry JD, Harrison G, Kaplan SL, et al (Eds), Elsevier, Philadelphia 2018. p.516.

3. Saavedra-Lozano J, Falup-Pecurariu O, Faust SN, et al. Bone and Joint Infections. Pediatr InfectDis J 2017; 36:788.

4. Harris JC, Caesar DH, Davison C, et al. How useful are laboratory investigations in the emergencydepartment evaluation of possible osteomyelitis? Emerg Med Australas 2011; 23:317.

evaluation generally includes advanced imaging with magnetic resonance imaging (MRI) orscintigraphy. If it is available, MRI is preferred to scintigraphy in view of its higher degree ofsensitivity and spatial resolution; however, scintigraphy may be better if symptoms are poorlylocalized or multiple areas of involvement are suspected, and can often be performed without theneed for sedation (table 1 and table 2). (See 'Advanced imaging' above.)

Specimens for Gram stain and culture should be obtained from as many sites of infection aspossible. Isolation of a pathogen from bone, periosteal collection, joint fluid, or blood confirms thediagnosis and speciation and susceptibility testing are essential for planning for the prolongedtreatment required for osteomyelitis. (See 'Microbiology' above.)

●

The diagnosis of osteomyelitis is confirmed by histopathologic evidence of inflammation in a surgicalspecimen of bone (picture 1A-C) (if obtained) or identification of a pathogen by culture or Gram stainin an aspirate of bone. (See 'Confirmed osteomyelitis' above.)

●

The diagnosis is probable in a child with compatible clinical, laboratory, and/or radiologic findings(table 1) in whom a pathogen is isolated from blood, periosteal collection, or joint fluid. We alsoconsider the diagnosis to be probable in a child with compatible clinical, laboratory, and radiologicfindings and negative cultures if he or she responds as expected to empiric antimicrobial therapy.(See 'Probable osteomyelitis' above.)

Osteomyelitis is unlikely if advanced imaging studies (usually MRI or scintigraphy) are normal. (See'Osteomyelitis unlikely (advanced imaging studies normal)' above.)

The differential diagnosis of osteomyelitis includes other infections, noninfectious conditions, andradiographic mimics (table 4). (See 'Differential diagnosis' above.)

●
















6. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Sensitivity of erythrocyte sedimentation rate and C-reactive protein in childhood bone and joint infections. Clin Orthop Relat Res 2010; 468:861.

7. Unkila-Kallio L, Kallio MJ, Eskola J, Peltola H. Serum C-reactive protein, erythrocyte sedimentationrate, and white blood cell count in acute hematogenous osteomyelitis of children. Pediatrics 1994;93:59.

8. Browne LP, Mason EO, Kaplan SL, et al. Optimal imaging strategy for community-acquiredStaphylococcus aureus musculoskeletal infections in children. Pediatr Radiol 2008; 38:841.

9. Jaramillo D, Dormans JP, Delgado J, et al. Hematogenous Osteomyelitis in Infants and Children:Imaging of a Changing Disease. Radiology 2017; 283:629.



12. Capitanio MA, Kirkpatrick JA. Early roentgen observations in acute osteomyelitis. Am J RoentgenolRadium Ther Nucl Med 1970; 108:488.

13. Overturf GD. Bacterial infections of the bones and joints. In: Infectious diseases of the fetus and newborn infant, 7th, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, PhiladelphiaVol 2011, p.296.

14. Mustafa MM, Sáez-Llorens X, McCracken GH Jr, Nelson JD. Acute hematogenous pelvicosteomyelitis in infants and children. Pediatr Infect Dis J 1990; 9:416.


16. Averill LW, Hernandez A, Gonzalez L, et al. Diagnosis of osteomyelitis in children: utility of fat-suppressed contrast-enhanced MRI. AJR Am J Roentgenol 2009; 192:1232.

17. Saigal G, Azouz EM, Abdenour G. Imaging of osteomyelitis with special reference to children.Semin Musculoskelet Radiol 2004; 8:255.

18. Connolly LP, Connolly SA, Drubach LA, et al. Acute hematogenous osteomyelitis of children:assessment of skeletal scintigraphy-based diagnosis in the era of MRI. J Nucl Med 2002; 43:1310.

19. Weber-Chrysochoou C, Corti N, Goetschel P, et al. Pelvic osteomyelitis: a diagnostic challenge inchildren. J Pediatr Surg 2007; 42:553.































20. McPhee E, Eskander JP, Eskander MS, et al. Imaging in pelvic osteomyelitis: support for earlymagnetic resonance imaging. J Pediatr Orthop 2007; 27:903.

21. Mazur JM, Ross G, Cummings J, et al. Usefulness of magnetic resonance imaging for thediagnosis of acute musculoskeletal infections in children. J Pediatr Orthop 1995; 15:144.

22. Pöyhiä T, Azouz EM. MR imaging evaluation of subacute and chronic bone abscesses in children.Pediatr Radiol 2000; 30:763.

23. Jaramillo D, Hoffer FA. Cartilaginous epiphysis and growth plate: normal and abnormal MR imagingfindings. AJR Am J Roentgenol 1992; 158:1105.

24. Kan JH, Hilmes MA, Martus JE, et al. Value of MRI after recent diagnostic or surgical intervention inchildren with suspected osteomyelitis. AJR Am J Roentgenol 2008; 191:1595.

25. Guillerman RP. Osteomyelitis and beyond. Pediatr Radiol 2013; 43 Suppl 1:S193.

26. Shih HN, Shih LY, Wong YC. Diagnosis and treatment of subacute osteomyelitis. J Trauma 2005;58:83.

27. Schmit P, Glorion C. Osteomyelitis in infants and children. Eur Radiol 2004; 14 Suppl 4:L44.

28. Kan JH, Young RS, Yu C, Hernanz-Schulman M. Clinical impact of gadolinium in the MRI diagnosisof musculoskeletal infection in children. Pediatr Radiol 2010; 40:1197.

29. Allwright SJ, Miller JH, Gilsanz V. Subperiosteal abscess in children: scintigraphic appearance.Radiology 1991; 179:725.

30. Tuson CE, Hoffman EB, Mann MD. Isotope bone scanning for acute osteomyelitis and septicarthritis in children. J Bone Joint Surg Br 1994; 76:306.

31. The Alliance for Radiation Safety in Pediatric Imaging. www.imagegently.org (Accessed on September 03, 2016).

32. Mok PM, Reilly BJ, Ash JM. Osteomyelitis in the neonate. Clinical aspects and the role ofradiography and scintigraphy in diagnosis and management. Radiology 1982; 145:677.

33. Bressler EL, Conway JJ, Weiss SC. Neonatal osteomyelitis examined by bone scintigraphy.Radiology 1984; 152:685.

34. Hoffer FA, Emans J. Percutaneous drainage of subperiosteal abscess: a potential treatment forosteomyelitis. Pediatr Radiol 1996; 26:879.

35. McNeil JC, Forbes AR, Vallejo JG, et al. Role of Operative or Interventional Radiology-GuidedCultures for Osteomyelitis. Pediatrics 2016; 137.































36. Ratnayake K, Davis AJ, Brown L, Young TP. Pediatric acute osteomyelitis in the postvaccine,methicillin-resistant Staphylococcus aureus era. Am J Emerg Med 2015; 33:1420.

37. Yeo A, Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ 2014; 348:g66.

38. Zhorne DJ, Altobelli ME, Cruz AT. Impact of antibiotic pretreatment on bone biopsy yield forchildren with acute hematogenous osteomyelitis. Hosp Pediatr 2015; 5:337.

39. Yagupsky P. Kingella kingae: from medical rarity to an emerging paediatric pathogen. Lancet InfectDis 2004; 4:358.

40. Centers for Disease Control and Prevention (CDC). Osteomyelitis/septic arthritis caused byKingella kingae among day care attendees--Minnesota, 2003. MMWR Morb Mortal Wkly Rep 2004;53:241.

41. Chometon S, Benito Y, Chaker M, et al. Specific real-time polymerase chain reaction placesKingella kingae as the most common cause of osteoarticular infections in young children. PediatrInfect Dis J 2007; 26:377.

42. Verdier I, Gayet-Ageron A, Ploton C, et al. Contribution of a broad range polymerase chain reactionto the diagnosis of osteoarticular infections caused by Kingella kingae: description of twenty-fourrecent pediatric diagnoses. Pediatr Infect Dis J 2005; 24:692.

43. El Houmami N, Minodier P, Dubourg G, et al. Patterns of Kingella kingae Disease Outbreaks.Pediatr Infect Dis J 2016; 35:340.

44. Lyon RM, Evanich JD. Culture-negative septic arthritis in children. J Pediatr Orthop 1999; 19:655.

45. Yagupsky P, Bar-Ziv Y, Howard CB, Dagan R. Epidemiology, etiology, and clinical features ofseptic arthritis in children younger than 24 months. Arch Pediatr Adolesc Med 1995; 149:537.

46. Perlman MH, Patzakis MJ, Kumar PJ, Holtom P. The incidence of joint involvement with adjacentosteomyelitis in pediatric patients. J Pediatr Orthop 2000; 20:40.

47. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Shortened hospital stay for childhood bone and jointinfections: analysis of 265 prospectively collected culture-positive cases in 1983-2005. Scand JInfect Dis 2012; 44:683.

48. Fox L, Sprunt K. Neonatal osteomyelitis. Pediatrics 1978; 62:535.

49. Harknett KM, Hussain SK, Rogers MK, Patel NC. Scurvy mimicking osteomyelitis: case report andreview of the literature. Clin Pediatr (Phila) 2014; 53:995.

































GRAPHICS

Imaging abnormalities in osteomyelitis

Imagingmodality

Abnormal findings

Plain radiograph* Deep soft tissue swelling (3 days after onset)

Periosteal reaction or elevation (10 to 21 days after onset)

Lytic sclerosis (≥1 month after onset)

Magnetic resonanceimaging

Bone marrow inflammation (decreased signal in T1-weighted images; increased signal in T2-weighted images)

Edema in marrow and soft tissues

Penumbra sign (high-intensity-signal transition zone between abscess and sclerotic bone marrowin T1-weighted images)

With gadolinium enhancement: absent blood flow, suggestive of necrosis or abscess

Three-phase bonescan

Focal uptake of tracer in the third phase (delayed phase)

Computedtomography

Increased density of bone marrow

Cortex destruction

Periosteal reaction (new bone formation) formation

Periosteal purulence

Sequestra (devitalized, sclerotic bone)

Ultrasonography Fluid collection adjacent to bone without intervening soft tissue

Thickening of periosteum

Periosteal elevation

* The timing and typical sequence of radiographic changes may vary with the site of infection and age of the patient.

References:1. Browne LP, Mason EO, Kaplan SL, et al. Optimal imaging strategy for community-acquired Staphylococcus aureus

musculoskeletal infections in children. Pediatr Radiol 2008; 38:841.2. Jaramillo D, Treves ST, Kasser JR, et al. Osteomyelitis and septic arthritis in children: Appropriate use of imaging to guide

treatment. AJR Am J Roentgenol 1995; 165:399.3. Saigal G, Azouz EM, Abdenour G. Imaging of osteomyelitis with special reference to children. Semin Musculoskelet Radiol

2004; 8:255.4. Schmit P, Glorion C. Osteomyelitis in infants and children. Eur Radiol 2004; 14 Suppl 4:L44.




Acute osteomyelitis






Progression of radiographic findings in a six-year-old boywith osteomyelitis of the fibula

(A) Plain radiographs (after one week of swelling and pain in the calf) wereinitially interpreted as normal.(B) A plain radiograph obtained four days after the initial films demonstratesperiosteal reaction and cortical thickening.(C) T1 weighted magnetic resonance image with gadolinium demonstratesenhancement of the fibula marrow space and surrounding soft tissues.

Courtesy of Marvin B Harper, MD.




Osteomyelitis with subperiosteal abscess

Radiograph of the femur demonstrates periosteal elevation due to asubperiosteal abscess as the result of osteomyelitis.





Lytic lucency in osteomyelitis

(A) Radiograph at the initial evaluation of a nine-year-old with fever and limpdemonstrates a lytic lucency in the distal femoral metaphysis.(B, C) Axial and coronal magnetic resonance (MR) images delineate the area ofosteomyelitis and adjacent marrow edema.

Reproduced with permission from Jeanne Chow, MD. Children's Hospital-Boston, Copyright ©Jeanne Chow, MD.




Early osteomyelitis in a six-year-old with fever and anklepain

Radiographs of the ankle (A) demonstrate deep soft tissue swelling (arrow)inferior to the medial malleolus. A technetium 99m bone scan showsincreased uptake in the distal tibia in the blood flow (B) and bone uptake (C;four hour) phases.





Osteomyelitis in a nine-year-old girl with knee pain andfever

(A) Plain radiographs of the knee are unremarkable.(B) T1 weighted MRI demonstrates marked decrease in signal intensity in themedial metaphysis and epiphysis of the distal femur. There is some involvementof the soft tissue.(C) These findings are more pronounced in a T1 weighted MRI with gadolinium.

MRI: magnetic resonance imaging.



¶



Comparison of imaging modalities in children with osteomyelitis

Modality Indications Advantages Disadvantages Comments*

Plain radiographs Baseline

Excluding otherconditions indifferential diagnosis

Monitoring diseaseprogression

Inexpensive

Easy to obtain

Abnormal findingsusually not present atonset of symptoms,except in newborns

Sensitivity 16 to 20percent

Specificity 80 to 100percent

Normal radiograph atonset does notexclude osteomyelitis

MRI Identify location andextent of disease

Evaluation of adjacentstructures forextension of infection(soft tissues, growthplate, epiphysis, joint)

Evaluation of difficultsites (eg, pelvis,vertebral bodies,intervertebral discs)

Planning surgicalintervention

No radiation risk

Demonstrates earlychanges in themarrow cavity

Improveddemonstration ofsubperiosteal abscess

Demonstration ofconcomitant septicarthritis, venousthrombosis, orpyomyositis

Costly

Less useful inmultifocal or poorlylocalized disease

Requires more timethan CT

Young children mayrequire sedation oranesthesia

Not always available

Sensitivity: 80 to 100percent

Specificity: 70 to 100percent

Osteomyelitis unlikelyif MRI is normal

Scintigraphy Poorly localizedsymptoms (eg, youngchildren who cannotverbalize)

Multifocal disease

More useful than MRIin multifocal or poorlylocalized disease

Demonstrates earlychanges

Readily available

May require lesssedation than MRI

Radiation exposure

Does not provideinformation aboutextent of purulentcollections that mayrequire drainage



Osteomyelitis unlikelyif scintigraphy isnormal

May be falselynegative if bloodsupply to periosteumis interrupted (eg,subperiosteal abscess)

CT Evaluation of corticaldestruction, bone gas,and sequestrum

Delineating extent ofbone injury insubacute/chronicosteomyelitis

Planning surgicalinterventions

Evaluation ofcomplications if MRInot available orcontraindicated

Less time-consumingthan MRI

Does not requiresedation

Expensive

Increased radiationexposure

Poor soft tissuecontrast

Sensitivity: 67 percent

Specificity: 50 percent

Generally used only ifother studies are notpossible orinconclusive

Ultrasonography Evaluate fluidcollections in adjacentstructures (eg, joint,periosteum)

Monitor abscessresolution orprogression

Inexpensive

No radiation burden

Noninvasive

Portable

Does not penetratebone cortex



MRI: magnetic resonance imaging; CT: computed tomography.* Values for sensitivity and specificity are from: Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and

¶



subacute paediatric osteomyelitis: A systematic review of the literature. J Bone Joint Surg Br 2012; 94:584.¶ Preferred imaging study when imaging other than plain radiographs are necessary to establish the diagnosis of osteomyelitis.

References:1. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatric osteomyelitis: A systematic

review of the literature. J Bone Joint Surg Br 2012; 94:584.2. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch Dis Child 2012; 97:545.3. Peltola H, Pääkkönen M. Acute osteomyelitis in children. N Engl J Med 2014; 370:352.4. Yeo A, Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ 2014; 348:g66.




Magnetic resonance image distal femoral osteomyelitisand subperiosteal abscess

Axial (A) and coronal (B) magnetic resonance images (post gadoliniuminfusion) of a seven-year-old with distal femoral osteomyelitis andsubperiosteal abscess. The abscess is posterior on the axial view (arrow) andmedial to the distal femur on the coronal view (arrow). The pus is dark andsurrounded by an enhancing rim.

Courtesy of William Phillips, MD, Texas Children's Hospital.




Magnetic resonance image demonstrating osteomyelitis

(A) The proximal shaft and metaphysis of the left tibia show an abnormalmottled appearance.(B) The marrow signal from the left tibia is abnormal. In addition, there issoft tissue inflammation surrounding the left tibia.

Courtesy of Sheldon L Kaplan, MD. Texas Children's Hospital.





Clinical features

























Differential diagnosis of osteomyelitis in children and adolescents

Condition Features that distinguish from osteomyelitis

Other infections

Septicemia

Cellulitis

Septic arthritis

Deep abscess

Pyomyositis

MRI or scintigraphy studies lack abnormalities characteristic ofosteomyelitis

Noninfectious conditions

Chronic nonbacterial osteomyelitis (eg,CRMO)

Multifocal lesions on imaging studiesLack of response to antimicrobial therapy

Malignancy (eg, primary bone tumor,leukemia)

Intermittent symptomsLack of response to antimicrobial therapyCharacteristic histopathology

Bone infarction in patients withhemoglobinopathy

Improvement with hydration and other supportive measures

Vitamin C deficiency (scurvy) Dietary history of limited vitamin C intakePetechiae, ecchymoses, bleeding gums, coiled hair, hyperkeratosis

Gaucher disease Characteristic radiographic featuresDysmorphic features on examination

Complex regional pain syndrome Autonomic dysfunctionNormal erythrocyte sedimentation rate, C-reactive protein

Caffey disease (infantile corticalhyperostosis)

Characteristic histopathology

Radiographic mimics*

Benign bone tumors:

Fibrous dysplasiaOsteoid osteomaOsteoblastomaChondroblastomaChondromyxoid fibroma

Absence of acute symptomsLack of response to antimicrobial therapyCharacteristic histopathology

Langerhans cell histiocytosis Characteristic histopathology

Malignant bone tumors:

Osteosarcoma Intermittent symptomsLack of response to antimicrobial therapyCharacteristic histopathology

MRI: magnetic resonance imaging; CRMO: chronic recurrent multifocal osteomyelitis.* Refer to UpToDate topics on benign bone tumors, Langerhans cell histiocytosis, and malignant bone tumors for additionalinformation about the radiographic appearance of these conditions.




Perifollicular abnormalities in scurvy

In this example, the perifollicular hyperkeratotic papules are quiteprominent, with surrounding hemorrhage. These lesions have beenmisinterpreted as "palpable purpura," leading to the mistaken clinicaldiagnosis of vasculitis.

Reproduced with permission from: Hirschmann JV, Raugi GJ. Adult scurvy. J AmAcad Dermatol 1999; 41:895. Copyright © 1999 Elsevier.







Hematogenous osteomyelitis in children: Management - UpToDate



Hematogenous osteomyelitis in children: ManagementAuthor: Paul Krogstad, MD Section Editors: Sheldon L Kaplan, MD, William A Phillips, MD Deputy Editor: Mary M Torchia,MD



INTRODUCTION

Osteomyelitis is an infection localized to bone. It is usually caused by microorganisms (predominantlybacteria) that enter the bone hematogenously. Other pathogenic mechanisms include direct inoculation(usually traumatic, but also surgical) or local invasion from a contiguous infection (eg, sinusitis, decubitusulcers, deep wound infections, periodontal disease). Risk factors for nonhematogenous osteomyelitisinclude open fractures that require surgical reduction, implanted orthopedic hardware (such as pins orscrews), and puncture wounds.

The management of hematogenous osteomyelitis in children will be discussed here. The epidemiology,microbiology, clinical features, evaluation, and diagnosis of osteomyelitis in children are discussedseparately:

ONGOING DIAGNOSTIC EVALUATION

Radiographs usually are obtained in the initial evaluation of suspected osteomyelitis. However, becauseradiographs may be normal early in the course, empiric antimicrobial therapy may be initiated beforeradiographic confirmation with advanced imaging studies (eg, magnetic resonance imaging [MRI],scintigraphy) has been accomplished. (See "Hematogenous osteomyelitis in children: Evaluation anddiagnosis", section on 'Normal plain radiographs'.)

For children with suspected osteomyelitis whose initial radiographs are normal, MRI or scintigraphytypically is performed within a few days to substantiate the diagnosis. If empiric antimicrobial therapy isinitiated before definitive imaging studies, cultures should be obtained from blood and suspected foci of

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infection (if possible). (See 'Pretreatment evaluation' below.)

MRI or scintigraphy (if available) may be useful for children whose initial radiographs demonstrated softtissue changes and periosteal reaction without characteristic changes in bone mineral density.Characteristic findings on MRI or scintigraphy support the diagnosis of osteomyelitis (table 1). (See"Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on 'Advanced imaging'.)

Osteomyelitis is unlikely among children who lack characteristic findings on MRI or scintigraphy. Othertypes of infection and noninfectious causes of bone pain must be reconsidered. (See "Hematogenousosteomyelitis in children: Evaluation and diagnosis", section on 'Differential diagnosis'.)

INDICATIONS FOR SURGERY

Surgical intervention may be required at the time of presentation or during antimicrobial therapy ifchildren fail to respond as expected or magnetic resonance imaging (MRI) indicates extensive bone/softtissue involvement that requires debridement [1-4]. Consultation with an orthopedist with pediatricexpertise is recommended early in the clinical course. (See "Hematogenous osteomyelitis in children:Evaluation and diagnosis", section on 'Overview'.)

Indications for surgical intervention include:

Lesions requiring surgical intervention usually are diagnosed with MRI. Computed tomography scans andradiographs also may reveal evidence of sequestra or involucra (sheaths of periosteal bone that formaround a sequestrum) and are sometimes useful to plan surgical intervention. (See "Hematogenousosteomyelitis in children: Evaluation and diagnosis", section on 'Advanced imaging'.)

ANTIMICROBIAL THERAPY

Indications — We recommend initiation of empiric antimicrobial therapy for most children with clinicalfeatures suggestive of osteomyelitis (eg, symptoms and signs of bone pain, elevated erythrocytesedimentation rate [ESR]/C-reactive protein [CRP]) and:

Need for drainage of subperiosteal and soft tissue abscesses and intramedullary purulence●

Debridement of contiguous foci of infection (which also require antimicrobial therapy)●

Excision of sequestra (ie, devitalized bone)●

Failure to improve after 48 to 72 hours of antimicrobial therapy (see 'Response to therapy' below)●

Characteristic imaging abnormalities (most commonly noted on initial magnetic resonance imaging[MRI]) (table 1) (see "Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on'Advanced imaging')

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Normal radiographs if advanced imaging is not immediately available (eg, within 24 hours) or●


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In children who are otherwise well or only mildly ill appearing, administration of empiric antibiotics may bedelayed for 24 to 48 hours until cultures can be obtained via surgery or interventional radiography. Therationale for this delay is that cultures from intraoperative and interventional radiology procedures areless often positive with longer periods of antimicrobial therapy prior to obtaining these specimens [5,6].

Pretreatment evaluation — Before initiating empiric antimicrobial therapy, cultures should be obtainedfrom blood and suspected foci of infection. A minimum of one blood culture (but preferably two) should beobtained. Empiric antimicrobial therapy is adjusted according to clinical response and culture andsusceptibility results (if a pathogen is isolated). (See "Hematogenous osteomyelitis in children: Evaluationand diagnosis", section on 'Microbiology' and 'Pathogen-directed therapy' below.)

Infectious disease specialist consultation may be warranted for immunocompromised patients (eg, thosewith sickle cell disease, chronic granulomatous disease [CGD]) because they often have infections withchallenging antimicrobial susceptibility profiles. (See 'Additional coverage for other pathogens' below.)

Empiric parenteral therapy — Antimicrobial therapy for osteomyelitis often is initiated before thediagnosis is confirmed. The risk of delaying treatment for bacteremic patients may be significant,particularly for those with community-associated Staphylococcus aureus. (See 'Outcome' below and"Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on'Staphylococcus'.)

Factors in choice of regimen — Initial antimicrobial therapy for acute hematogenous osteomyelitisusually is administered parenterally. The empiric regimen is determined by the most likely pathogens andantimicrobial susceptibilities based on epidemiologic factors, including the child's age (table 2), clinicalfeatures (table 3), whether the infection is life threatening, and organisms prevalent in the community(algorithm 1). An additional consideration is the future ease of transition to an oral regimen so thatindwelling intravenous catheters can be avoided. Thus, single (versus multiple) drug intravenous therapyand having an effective, palatable, oral counterpart may prove beneficial, particularly if no pathogens arerecovered by any cultures. (See 'Switch to oral therapy' below.)

Systematic reviews of randomized and observational studies have provided a general guide to the choiceof antibiotics for acute osteomyelitis in children [7-10]. In individual studies, the clinical cure rates foracute hematogenous osteomyelitis in children generally are >95 percent when empiric therapy is chosenaccording to age, underlying medical condition, and organisms that are prevalent in the community. Mostof the cases in the systematic reviews were confirmed to be caused by gram-positive pathogens(predominantly S. aureus), but a positive culture was not always required for study inclusion.

Children younger than three months — For empiric parenteral therapy in children younger than

feasible, particularly if they are ill appearing or have signs of sepsis; characteristic radiographicfeatures of osteomyelitis are not usually apparent on plain radiographs until 10 days after symptomonset (see 'Ongoing diagnostic evaluation' above and "Hematogenous osteomyelitis in children:Evaluation and diagnosis", section on 'Plain radiographs')

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three months with suspected osteomyelitis, we use a third- or fourth-generation cephalosporin combinedwith an antistaphylococcal agent (table 4). Third generation cephalosporins include cefotaxime (ifavailable), ceftazidime, or ceftriaxone; cefepime is a fourth generation cephalosporin. Antistaphylococcalagents include vancomycin, nafcillin/oxacillin, or cefazolin; cefazolin is an option for infants age one tothree months in whom central nervous system infection has been excluded. For infants with allergy orintolerance to cephalosporins (very uncommon in this age group), we suggest consultation with an expertin pediatric infectious diseases.

This empiric regimen provides coverage for the most common causes of hematogenous osteomyelitis inthis age group: S. aureus, gram-negative bacilli, and group B Streptococcus. (See "Hematogenousosteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Microbiology'.)

Cefotaxime is the preferred third-generation cephalosporin. If cefotaxime is not available, ceftazidime orthe fourth-generation cephalosporin cefepime are the preferred alternatives. Ceftriaxone is anotheralternative for infants who are not receiving intravenous calcium-containing solutions [11] but generally isavoided in young infants because of the theoretic increased risk of kernicterus.

Vancomycin is the preferred initial antistaphylococcal agent for infants:

At some institutions, clindamycin is used as an alternative to vancomycin if less than 10 percent of S.aureus isolates are methicillin resistant and less than 10 percent are clindamycin resistant, and the infanthas localized infection with no signs of sepsis. Other experts may use a different threshold forclindamycin resistance. (See 'Children three months and older' below.)

Children three months and older — Empiric intravenous antimicrobial therapy for children older thanthree months should be directed against S. aureus (the most common cause of hematogenousosteomyelitis in this age group) and other gram-positive organisms (eg, group A streptococci,Streptococcus pneumoniae). Broader empiric therapy may be necessary for special populations. (See'Additional coverage for other pathogens' below.)

Agents that provide antistaphylococcal and antistreptococcal coverage include nafcillin/oxacillin,cefazolin, clindamycin, and vancomycin. We do not generally use trimethoprim-sulfamethoxazole (TMP-SMX) for suspected community-associated MRSA (CA-MRSA) osteomyelitis in children because of thelimited data supporting its efficacy and the high rate of mild adverse events [12]. (See "Staphylococcusaureus in children: Overview of treatment of invasive infections".)

The choice of regimen depends on whether the infection is life threatening (eg, the child has signs ofsepsis), the local prevalence of CA-MRSA, and the susceptibility of CA-MRSA to clindamycin [1,13,14].

Who have been in an intensive care unit for more than one week (increased risk for hospital-acquired methicillin-resistant S. aureus (MRSA) or coagulase-negative staphylococci)

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Whose mothers have or are suspected to have infection or colonization with community-acquired S.aureus (increased risk of methicillin resistance)

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Coverage for gram-positive pathogens

A 2013 systematic review of three randomized trials and 22 observational studies addressing the choiceof antibiotics found limited evidence to definitively guide the choice of antibiotics for acute osteomyelitis inchildren [9]. There is evidence from a quasi-randomized trial that first-generation cephalosporins (eg,cefazolin) and clindamycin are similarly effective treatments for acute osteomyelitis in children >3 monthsof age in an area with a low prevalence of MRSA and Kingella kingae [18].

Additional coverage for other pathogens — It may be necessary to add empiric coverage for

Life-threatening infection – For gram-positive coverage in children ≥3 months with acutehematogenous osteomyelitis and life-threatening infection (eg, signs of sepsis), we suggestvancomycin plus either nafcillin or oxacillin; we provide empiric antimicrobial therapy for otherpathogens as indicated. Nafcillin or oxacillin is the preferred therapy for methicillin-susceptible S.aureus (MSSA). For children unable to tolerate penicillins, we use vancomycin alone. (See'Additional coverage for other pathogens' below.)

●

Non-life-threatening infection – For gram-positive coverage in children ≥3 months with acutehematogenous osteomyelitis and non-life-threatening infection:

●

We suggest nafcillin/oxacillin or cefazolin if <10 percent of the community S. aureus isolates aremethicillin resistant. For children who are unable to tolerate penicillin and cephalosporinantibiotics, we suggest clindamycin if <10 percent of S. aureus isolates are clindamycinresistant. Other experts may use a different threshold for clindamycin resistance.

•

We suggest either vancomycin or clindamycin if ≥10 percent of the community S. aureusisolates are methicillin resistant [13,14].

•

We suggest vancomycin for children who have underlying frequent contact with the healthcare system or who were hospitalized in the past six months because these children havean increased risk of clindamycin resistance.

-

We suggest vancomycin when ≥10 percent of S. aureus isolates in the community also areresistant to clindamycin (constitutive and inducible) [15,16]. Other experts may use adifferent threshold for clindamycin resistance. (See "Overview of antibacterial susceptibilitytesting", section on 'Inducible clindamycin resistance testing'.)

-

We suggest clindamycin for children with localized infection and no signs of sepsis ifclindamycin resistance is not a concern based on local patterns of antimicrobial drugresistance.

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Alternatives to vancomycin or clindamycin when MRSA is a concern include linezolid or daptomycin(daptomycin only if the child is ≥1 year of age and has no concomitant pulmonary involvement)[13,14,17].




















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pathogens other than S. aureus (and other gram-positives) when clinical or laboratory factors suggest aspecific pathogen (table 3). (See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis,and microbiology", section on 'Microbiology'.)

Preschool children in day care – K. kingae should be considered as a possible pathogen inchildren 6 to 36 months of age (especially those attending day care) and those with indolentosteomyelitis or a history of oral ulcers preceding the onset of musculoskeletal findings [19-27]. K.kingae usually is susceptible to cephalosporins (eg, cefazolin) but is consistently resistant tovancomycin and often resistant to clindamycin and antistaphylococcal penicillins (eg, oxacillin,nafcillin) [23,24].

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We generally do not provide initial empiric coverage for K. kingae in young children because mostcases of osteomyelitis in the United States are caused by S. aureus and other gram-positivepathogens. In addition, initial multidrug therapy may complicate transition to oral therapy if anorganism is not identified in culture. K. kingae generally causes relatively mild musculoskeletalinfections; chronic osteomyelitis and other complications requiring surgical interventions are rare[24,28,29].

For children between 6 and 36 months of age who require vancomycin or clindamycin for empiriccoverage of CA-MRSA, empiric coverage for K. kingae with cefazolin may be added if the child doesnot improve as expected. Alternatively, cefazolin may be substituted for vancomycin or clindamycin ifCA-MRSA is not identified in cultures of blood, bone, or soft tissue aspirates. (See 'Culture-negativeosteomyelitis' below and "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, andmicrobiology", section on 'Microbiology'.)

Incomplete Haemophilus influenzae type b immunization – We add coverage for H. influenzaetype b (Hib) (eg, cefotaxime, ceftriaxone) in children <2 years who have not been fully immunizedagainst Hib (table 5) who are from areas where Hib immunization rates are low. Coverage for Hib isnot necessary for children from areas with high Hib immunization rates. Regional vaccinationcoverage estimates for children 19 to 35 months are available from the Centers for Disease Controland Prevention.

●

Sickle cell disease or reptile exposure – We add empiric coverage for Salmonella and other gram-negative bacilli (eg, cefotaxime, ceftriaxone) for children with sickle cell disease. Salmonella is acommon cause of osteomyelitis in children with sickle cell disease [30,31]. Salmonella should alsobe considered in children with osteomyelitis and reptile or amphibian exposure and/orgastrointestinal symptoms [32]. (See "Acute and chronic bone complications of sickle cell disease",section on 'Osteomyelitis and septic arthritis'.)

●

Chronic granulomatous disease – Addition of a third-generation cephalosporin (eg, cefotaxime,ceftriaxone) to initial empiric therapy is prudent for patients with CGD. In individuals with CGD,osteomyelitis frequently is caused by unusual organisms (eg, Aspergillus and other fungi, Serratiaspecies, and other filamentous or gram-negative bacteria), as well as staphylococci [33,34].

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Pathogen-directed therapy — The antimicrobial regimen can be tailored to a specific pathogen whenculture and susceptibility results are available (table 6) [10]. Doses are provided in the table (table 4).Consultation with an expert in infectious diseases is suggested for children with an inadequate responseto therapy, unusual organisms, and/or drug allergies.

Culture-negative osteomyelitis — No organism is identified in approximately 50 percent of children withsuspected osteomyelitis [10]. The decision to continue empiric antibiotic therapy is based upon the initialclinical suspicion, advanced imaging studies, and response to empiric therapy. Most cases can bemanaged with regimens that are appropriate for culture-positive cases in a given geographical location,and failures of treatment are rare. We generally use therapy appropriate for MSSA (eg, cefazolin,nafcillin, oxacillin) and monitor for response to therapy. Other experts may use clindamycin, particularly inareas with high rates of CA-MRSA (if rates of clindamycin resistance are low). (See 'Response totherapy' below.)

However, before committing the child to a long course of antibiotic therapy, the differential diagnosis mustbe reconsidered and likely alternative diagnoses excluded. This is particularly important for childrenwhose imaging studies remain negative. (See "Hematogenous osteomyelitis in children: Evaluation anddiagnosis", section on 'Differential diagnosis'.)

Improvement with empiric therapy — For children who present with characteristic clinical andradiographic features of osteomyelitis and have negative cultures, but improve rapidly with empirictherapy, continuation of empiric antimicrobial therapy generally is warranted.

Debridement combined with voriconazole has proven successful in some patients with invasive boneAspergillus [34]. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, anddiagnosis", section on 'Infections' and "Chronic granulomatous disease: Treatment and prognosis",section on 'Treatment'.)

Recent gastrointestinal surgery or complex urinary tract anatomy – Addition of 1) a third- orfourth-generation cephalosporin (eg, cefotaxime, ceftriaxone, cefepime) or 2) an aminoglycoside (eg,gentamicin) to the initial empiric regimen may be warranted for patients with recent gastrointestinalsurgery or complex urinary tract anatomy. Such patients are at risk for infection with enteric gram-negative organisms.

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Injection drug users – Organisms that cause infection among injection drug users (IDU) varymarkedly between communities. Pseudomonas aeruginosa frequently has been reported amongIDUs with osteomyelitis.

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If P. aeruginosa osteomyelitis is a consideration, we suggest that ceftazidime be added to empiricantistaphylococcal therapy with vancomycin, nafcillin, or oxacillin; this combination covers othergram-negative bacilli as well as S. aureus. (See "Pseudomonas aeruginosa skin and soft tissueinfections" and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections".)











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They may be switched to oral therapy focused on likely common pathogens (eg, S. aureus,Streptococcus pyogenes) if the clinical course is uncomplicated and they meet criteria for oral therapy.(See 'Switch to oral therapy' below.)

Continuation of empiric therapy directed toward gram-positive pathogens, particularly S. aureus, inchildren with culture-negative osteomyelitis is supported by a retrospective review in which outcomeswere similar between 45 children with culture-positive osteomyelitis (42 percent with MSSA, 31 percentwith MRSA) and 40 children with culture-negative osteomyelitis who received antistaphylococcalantibiotics [35]. A prospective study also found similar outcomes in 80 Finnish children with culture-negative osteoarticular infections who were treated with clindamycin or first-generation cephalosporins (8also received amoxicillin or ampicillin) and 265 children with culture-positive osteoarticular infections (75percent MSSA, 10 percent Hib, 9 percent S. pyogenes, and 5 percent S. pneumoniae) [36]. Thesefindings may not be generalizable because the proportion of cases caused by MRSA variesgeographically [10]; MRSA is commonly encountered in the United States. (See "Hematogenousosteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Staphylococcus'.)

Given the possibility of MRSA osteomyelitis, with associated increased risk of complications, it isessential to monitor the clinical and inflammatory response to empiric antimicrobial therapy in childrenwith culture-negative osteomyelitis. (See 'Response to therapy' below.)

Lack of improvement with empiric therapy — Lack of improvement or worsening during empiricparenteral antimicrobial therapy in children with clinical and radiographic features of osteomyelitis andnegative cultures may indicate:

The evaluation and management of these possibilities is discussed below. (See 'Lack of improvement orworsening' below.)

Response to therapy

Monitoring response — The response to therapy is assessed with serial clinical, laboratory, andimaging evaluations (table 7). During hospitalization, we monitor:

Development of a complication (eg, periosteal or soft tissue abscess, venous thrombosis)●

Ineffective antimicrobial therapy (eg, unusual or resistant pathogen, polymicrobial infection,inadequate dose of antibiotic agent or failure to administer it)

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A diagnosis other than osteomyelitis●

Clinical status (eg, fever, pain, localized erythema or swelling, new sites of infection) at least daily.●

CRP if clinical status worsens and every two to three days until CRP has demonstrated a >50percent reduction or steady decline, then weekly.

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CRP and ESR have both been used to monitor response in children with acute osteomyelitis.



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Expected response — In children with acute hematogenous osteomyelitis who are receivingappropriate and effective antimicrobial therapy, clinical improvement usually occurs within three to fourdays. Clinical and laboratory improvement is indicated by:

Clinical and laboratory improvement suggests that the diagnosis and choice of antimicrobial therapy arecorrect; continued improvement may be an indication for outpatient therapy. (See 'Switch to oral therapy'below.)

Lack of improvement or worsening — Lack of improvement or worsening is defined by:

However, the ESR typically increases during the first several days of treatment and consequentlydoes not usually play a role in the management during the initial hospitalization. CRP also increasesearly in the infection but returns to normal much more rapidly than ESR (eg, one week versus threeto four weeks in a systematic review [10]), which makes it more useful in monitoring the response totherapy [37-40]. Increase in CRP on or after the fourth day of treatment (if it is not associated withsurgical interventions) may be associated with a complicated clinical course (eg, prolongedsymptoms, progression of radiographic changes, need for repeat surgical intervention) [41-43]. (See"Hematogenous osteomyelitis in children: Clinical features and complications", section on'Laboratory features'.)

White blood cell (WBC) count before the switch to oral therapy if it was elevated at the time ofdiagnosis.

●

Elevations in the peripheral WBC count in children with hematogenous osteomyelitis are variable,present in only approximately one-third of patients [10], and nonspecific. The peripheral WBC count,if initially elevated, usually normalizes within 7 to 10 days after initiation of effective antimicrobialand/or surgical therapy.

Radiographs if clinical status worsens or fails to improve (to evaluate development of complications;areas of devitalized bone [sequestra] become evident within two to four weeks); additional imaging,usually with MRI, may be necessary. (See 'Lack of improvement or worsening' below.)

●

Resolution of fever●

Decreased pain and erythema or swelling●

Decrease in peripheral WBC (if initially elevated) and a drop in CRP of ≥50 percent every two tothree days

●

Worsening pain or extension of infection (eg, to the adjacent soft tissues, joint)●

Persistent fever, pain, and discomfort with movement after five days in toddlers and seven days inolder children and adolescents

●

Failure of CRP to decline by ≥50 percent after one week of therapy and to continue to decline during●




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Patients who are not responding to treatment as expected require reevaluation and adjustment oftherapy. Consultation with an expert in infectious diseases may be helpful if adjustments to antimicrobialtherapy are indicated. Lack of improvement or worsening may indicate [2,4]:

the second week [37]

Progression of radiographic abnormalities in affected bones (eg, development of abscess,sequestra)

●

Development of a complication requiring surgical intervention (eg, soft tissue, subperiosteal, orintramedullary abscess; sinus tract; sequestra) (see 'Indications for surgery' above)

●

Prompt evaluation is warranted and may include ESR and/or CRP, WBC count, and plain radiographof the affected area; further imaging, usually with MRI, may be necessary to identify a lesionrequiring surgery [44]. Although repeat imaging may identify residual infection or other sites ofinfection, in children who have undergone surgical intervention, it can be difficult to distinguishpostsurgical changes (eg, hematoma) from a recurrent abscess. (See 'Indications for surgery'above.)

Thromboembolism (see "Venous thrombosis and thromboembolism in children: Risk factors, clinicalmanifestations, and diagnosis", section on 'Clinical manifestations')

●

Ineffective antimicrobial therapy (eg, unusual or resistant pathogen, polymicrobial infection,inadequate dose of antibiotic)

●

An aggressive attempt must be made to isolate or identify fastidious (eg, K. kingae) and unusualpathogens (eg, Brucella, Bartonella henselae, fungi, mycobacteria) if appropriate exposures areidentified (table 3).

A bone biopsy should be obtained for histopathologic staining and culture for bacteria, mycobacteria,and fungi; injection of bone aspirates or periosteal collections into blood culture bottles isrecommended to enhance recovery of Kingella [45,46]. Polymerase chain reaction (if available) canbe particularly helpful for detecting K. kingae in purulent materials or bone specimens [26]. (See"Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", sectionon 'Microbiology' and "Hematogenous osteomyelitis in children: Evaluation and diagnosis", sectionon 'Microbiology'.)

Consultation with an expert in infectious diseases may be helpful if adjustments to antimicrobialtherapy are indicated. Inclusion of coverage for K. kingae (eg, penicillin, cephalosporin) may bewarranted for children between 3 and 36 months of age who were initially treated with vancomycin orclindamycin.

A diagnosis other than osteomyelitis (see "Hematogenous osteomyelitis in children: Evaluation anddiagnosis", section on 'Differential diagnosis')

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Switch to oral therapy — There is no minimum duration of intravenous therapy for treatment ofosteomyelitis [7]. Patients who are older than one month with uncomplicated osteomyelitis can beswitched from intravenous to oral therapy after they have demonstrated unequivocal clinicalimprovement, as indicated by [47-49]:

This usually occurs after 5 to 10 days of antimicrobial therapy [37,41,47,50,51].

Oral therapy avoids the risks of prolonged intravenous antibiotic administration via central venouscatheters [52-54]. (See 'Response to therapy' above.)

In randomized trials and observational studies, treatment of osteomyelitis with intravenous antibiotics forshort periods (approximately seven days) followed by oral therapy was as successful as longer coursesof parenteral therapy [7,9,10,52,54].

Lack of fever for ≥48 hours●

Decreased pain, erythema, or swelling●

Normalization of WBC count●

Consistent decrease in CRP●

Prerequisites – Our prerequisites for switching to oral from parenteral therapy include:●

Age ≥1 month – The gastrointestinal absorption of oral antibiotics in neonates <1 month isunpredictable [55,56]; we provide their entire course of antimicrobial therapy parenterally.

•

The clinical course has been uncomplicated.•

The child is immune competent and fully immunized against H. influenzae and S. pneumoniaefor his or her age (table 5).

•

If a pathogen is identified, it is susceptible to oral antibiotics.•

If cultures are negative, the child has responded as expected to empiric parenteral therapy andthere is an oral regimen with a spectrum similar to the parenteral regimen.

•

The child has demonstrated ability to swallow, retain, and absorb an appropriate oralmedication; the initial doses of oral therapy should be administered while the child is in thehospital to ensure that the drug is tolerated.

•

The patient and family have received appropriate education, are committed to the follow-upschedule, and are expected to adhere to the antimicrobial regimen.

•

Outpatient parenteral antimicrobial therapy (OPAT) may be warranted for patients withcontraindications to oral therapy who have improved as expected with parenteral therapy. Insertionof a percutaneously inserted central catheter facilitates prolonged administration of parenteralantibiotics and can be used for OPAT. However, catheter-related complications (eg, malfunction,displacement, bloodstream infection) occur in 30 to 40 percent of children with osteoarticular



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Choice of oral regimen — The choice of oral therapy depends upon whether an organism was isolatedfrom blood, bone (if obtained), or other culture. Additional considerations include bioavailability andpalatability of the oral medication. Consultation with an expert in infectious diseases may be helpful inchoosing the optimal oral agent, particularly if the child has an unusual pathogen or allergy to antibiotics.

When an organism is isolated, the susceptibility pattern can be used to determine an appropriate drug(table 6).

When an organism is not isolated, oral therapy is directed toward the most likely pathogen(s) given thechild's age (table 2) and clinical presentation (table 3). The chosen regimen should have a spectrumsimilar to that provided by the parenteral therapy that was associated with improvement. As examples, achild who improved with cefazolin may be switched to cephalexin; a child who improved with parenteralclindamycin may be switched to oral clindamycin.

To ensure adequate bone penetration, antibiotics administered orally for hematogenous osteomyelitisgenerally are given in higher doses than those for treatment for other infections and recommended inpackage inserts (table 8) [47,58-60]. To achieve adequate serum levels, doses of beta-lactams(penicillins and cephalosporins other than cefixime) often can be increased to 100 to 150 mg/kg per daywithout serious adverse side effects.

We do not generally use oral TMP-SMX for CA-MRSA osteomyelitis in children because it has not beenprospectively studied for this indication. However, there are some retrospective data that it may beeffective [12].

Total duration

Confirmed or probable osteomyelitis — We suggest that children with confirmed or probableuncomplicated osteomyelitis be treated with antimicrobial therapy for a minimum of four weeks. The totalduration for individual patients is determined by the clinical and radiographic response to therapy andnormalization of inflammatory markers. (See "Hematogenous osteomyelitis in children: Evaluation anddiagnosis", section on 'Diagnostic interpretation'.)

We administer antimicrobial therapy for four weeks and until the ESR and CRP are normal [1,47,50,61],whichever is longer, regardless of pathogen or complications. Other experts may not use normalizationof ESR as a criterion for discontinuation of antimicrobial therapy or may document normalization of ESRonly in children with osteomyelitis caused by MRSA [62] and in cases that have been initially complicated(eg, concomitant septic arthritis, intraosseous or periosteal abscess or lytic bone lesions at presentation,requiring repeated surgical management of soft tissue foci, delayed normalization of CRP beyond theexpected 7 to 10 days).

Courses longer than four weeks may be necessary for children who require surgical debridement, havedelayed clinical improvement or persistent elevation of CRP, have MRSA or Panton-Valentine leukocidin-

infections who are treated with OPAT [53,57].





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positive osteomyelitis, or have underlying medical conditions [10]. (See 'Outcome' below.)

Before discontinuing antimicrobial therapy, we also generally obtain a radiograph to make sure there areno new bone lesions (eg, devitalized bone [sequestra], lytic lesions), even if there is no clinical evidenceof treatment failure. However, we discuss the need for and timing of subsequent radiographs with thepediatric orthopedist involved in the evaluation. Delaying the radiograph to allow initial or expectedabnormalities to resolve is an alternative approach. (See 'Lack of improvement or worsening' above.)

A 2013 systematic review found limited evidence to strictly define the optimal duration of antimicrobialtherapy for acute hematogenous osteomyelitis [9]. In the a randomized trial conducted in Finland,children with culture-proven osteomyelitis recovered completely whether they were treated for 20 or 30days, provided that they had a good clinical response and rapid normalization of CRP [63]. However, thegeneralizability of these results is limited because there were minimal complications and 89 percent ofcases were caused by MSSA. The proportion of cases caused by MRSA varies geographically but iscommon in the United States [38,39]. MRSA osteomyelitis requires increased duration of therapy, andsome experts do not stop antimicrobial treatment until both the ESR and CRP have normalized. (See"Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on'Staphylococcus'.)

In observational studies, treatment failure appears to be more common with total duration ≤3 weeks thanwith treatment ≥4 weeks [7,48,64,65]. Consequently, we advise treatment for a minimum of four weeksand extend the duration if inflammatory markers and clinical findings remain abnormal.

Osteomyelitis unlikely — Osteomyelitis is unlikely if advanced imaging studies (usually MRI orscintigraphy) are normal. Decisions about continuation and duration of antimicrobial therapy should bemade on a case-by-case basis. The results of the blood culture and response to antimicrobial therapy areimportant considerations in this decision.

Positive blood culture, improvement with empiric therapy – Pathogen-directed antimicrobialtherapy is warranted unless a source of infection other than osteomyelitis is identified. (See"Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on 'Other infections'.)

●

Positive blood culture, no improvement with empiric therapy – Continuation of pathogen-directed antimicrobial therapy is warranted pending evaluation for other sources of bacteremia andnoninfectious conditions that may have predisposed the patient to bacteremia. (See "Hematogenousosteomyelitis in children: Evaluation and diagnosis", section on 'Differential diagnosis'.)

●

Negative blood culture, improvement with empiric therapy – A shorter course of empiricantimicrobial therapy for a more superficial source of infection (eg, cellulitis) may be warranted. (See"Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on 'Other infections'.)

●

Negative blood culture, no improvement with empiric therapy – Empiric antimicrobial therapyusually can be discontinued; further investigation for pathogens not covered by empiric therapy maybe necessary. Noninfectious causes of musculoskeletal pain should be sought. (See

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Drug monitoring

OTHER THERAPIES

Immobilization — Immobilization of the affected extremity may relieve pain. It also may preventpathologic fractures when bone involvement is extensive as detected by radiography or other imagingmodalities. Immobilization may be particularly important for children with osteomyelitis of the proximalfemur or vertebral osteomyelitis and children with methicillin-resistant S. aureus (MRSA) osteomyelitis[70].

We suggest protected weight-bearing and activity restriction for children with risk factors for pathologicfracture until inflammatory markers have returned to normal, the involved bone appears normal onradiographs, and the child is pain free. Risk factors for pathologic fracture include [70]:

"Hematogenous osteomyelitis in children: Evaluation and diagnosis", section on 'Noninfectiousconditions'.)

Adverse effects – Children who are being treated with parenteral or oral antibiotic therapy forosteomyelitis require monitoring for potential adverse effects. Adverse effects of high-dose antibiotictherapy may include pancytopenia, leukopenia, hepatitis [66], impaired liver or renal function, andantibiotic-associated diarrhea [67,68].

●

The monitoring schedule varies depending upon the drug, dose, and route of therapy. We obtaincomplete blood count (CBC; with differential) weekly initially, while the patient is receiving beta-lactam antibiotics (eg, penicillins, cephalosporins). We also obtain a biochemical profile, includingserum aminotransferases, weekly while the patient is receiving penicillin antibiotics or parenteralcephalosporins. Some experts also obtain laboratory studies every one to two weeks forclindamycin, although hematologic adverse effects are less of a concern. For linezolid, CBCs shouldbe monitored weekly for therapy beyond two weeks. (See 'Follow-up' below.)

Adequacy of therapy – We generally do not monitor concentrations of antimicrobial agents exceptfor children receiving oral therapy whose clinical findings and inflammatory markers do not improveas expected. Rare patients have inadequate serum concentrations despite high oral doses [61]. Wemonitor adequacy of therapy and adherence by following ESR and CRP.

●

Although serum bactericidal titers have historically been used to monitor the adequacy of drugtherapy, they are not widely available and require isolation of an organism [69].

Prolonged hospital stay●

Multiple surgical procedures●

Maximum circumferential extent of abscess ≥50 percent of bone circumference on magneticresonance imaging (MRI)

●

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Thromboembolism — Patients with associated deep vein thrombosis and/or septic pulmonary emboliare usually managed in conjunction with a hematologist. Management typically involves anticoagulationand continuation of antimicrobial therapy until the thrombus has resolved on Doppler imaging. (See"Venous thrombosis and thromboembolism in children: Treatment, prevention, and outcome", section on'Anticoagulant agents'.)

FOLLOW-UP

Children who are being treated as outpatients for osteomyelitis with either intravenous or oral antibioticsshould be seen at one- to two-week intervals. They should be monitored for continued clinicalimprovement and adverse effects of high-dose antibiotic therapy (eg, pancytopenia, leukopenia, impairedliver or renal function, antibiotic-associated diarrhea, pseudomembranous colitis). At each visit, we obtainC-reactive protein (CRP) and complete blood count (with differential); we also obtain a biochemicalprofile, including serum aminotransferases if the patient is receiving beta-lactam antibiotics (eg,penicillins, intravenous cephalosporins). (See 'Drug monitoring' above.)

For children with complicated osteomyelitis (eg, concomitant septic arthritis, intraosseous or periostealabscess or lytic bone lesions at presentation, requiring repeated surgical management of soft tissue foci,delayed normalization of CRP [beyond the expected 7 to 10 days]), we obtain erythrocyte sedimentationrate when treatment discontinuation is being considered. We also generally obtain radiographs of theaffected area(s) before discontinuation of antibiotics to make sure there are no new bone lesions. (See'Total duration' above.)

No specific follow-up for uncomplicated osteomyelitis is necessary after discontinuation of antibiotics inchildren who have had an uneventful resolution of all clinical findings, although some surgeons may electto follow children for 6 to 12 months to assess the growth of long bones, particularly those withcomplicated, extensive, or poorly responsive infections. This may be of particular importance if thegrowth plate (physis) was affected by the focus of infection. We counsel patients to seek attention ifsymptoms return in the area of initial confirmed or suspected osteomyelitis, noting that recrudescencesmay occur after prolonged periods of time. We also counsel families to watch for symptoms ofClostridioides (formerly Clostridium) difficile infection (eg, diarrhea, abdominal pain, abdominaldistension). (See "Clostridioides (formerly Clostridium) difficile infection in children: Clinical features anddiagnosis", section on 'Symptomatic disease'.)

OUTCOME

Most newborns, infants, and children who receive prompt, appropriate antimicrobial therapy before

Sharp zone of diminished marrow enhancement on MRIInfection caused by USA300-0114 MRSA pulsotype, including USA300 methicillin-susceptible S.aureus strains

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extensive bone necrosis develops have excellent outcomes. In systematic reviews and observationalstudies, >95 percent of patients have complete resolution of radiographically apparent bone damage[7,48,71].

The causative organism and location of infection may influence outcomes, particularly in neonates.

In a 2012 systematic review, risk factors for worse prognosis included [10]:

Despite adequate therapy, recurrence of infection may occur in 1 to 2 percent of children with acutehematogenous osteomyelitis, and others may develop significant complications such as chronicosteomyelitis, limp, and leg length discrepancy [18,71].

Among neonates with osteomyelitis, the prognosis is generally better for group B streptococcal infectionthan staphylococcal infection [73,74]. Sequelae of neonatal osteomyelitis result from the extension ofinfection into the subperiosteal space and soft tissue, involvement of the growth plate, and the spread ofinfection into the adjacent joint space (figure 1). Destruction of the growth plate may be associated withgrowth disturbance (angular deformity, shortening or overgrowth of the affected bone) [75,76]. Othersequelae of neonatal osteomyelitis include osteonecrosis (avascular necrosis) of the femoral head andbony deformities. Among newborns with vertebral osteomyelitis, collapse or complete destruction of oneor more vertebral bodies may occur, with kyphosis or spinal cord compression (and resultant paralysis)as late complications [77]. (See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis,and microbiology", section on 'Pathogenesis' and "Hematogenous osteomyelitis in children: Clinicalfeatures and complications", section on 'Complications'.)

Long-term sequelae are uncommon in older infants and children. However, multifocal disease, pathologicfractures, abnormal bone growth, chronic osteomyelitis, and the need for repeated surgical interventionhave been reported frequently among patients with community-associated methicillin-resistantstaphylococcal infection [59]. (See "Methicillin-resistant Staphylococcus aureus infections in children:Epidemiology and clinical spectrum", section on 'Community-onset'.)

In a case series of patients with S. aureus osteomyelitis from a single institution, 17 (4.7 percent)developed pathologic long-bone fractures; 15 of the 17 had MRSA [70]. Risk factors for pathologicfracture included prolonged hospital stay, multiple surgical procedures, large circumferentialsubperiosteal abscess (ie, maximum circumferential extent of abscess ≥50 percent of bone

Methicillin-resistant S. aureus (MRSA), S. pneumoniae, or Panton-Valentine leukocidin-positive S.aureus as the infecting organism

●

Concurrent septic arthritis, pyomyositis, or abscess●

Involvement of the hip (40 percent risk of complications), ankle (33 percent complications), or knee(10 percent complications) [72]

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Positive culture●

Younger age (possibly related to delays in presentation, diagnosis, and treatment)●

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circumference on magnetic resonance imaging [MRI]), sharp zone of diminished marrow enhancementon MRI, and USA300-0114 pulsotype. We suggest that children known to have these risk factors bemanaged with protected weight-bearing and activity restriction until inflammatory markers have returnedto normal, the involved bone appears normal on radiographs, and the child is pain free.

CHRONIC OSTEOMYELITIS

Chronic osteomyelitis is defined by signs and symptoms of bone inflammation for at least two weeks andradiographic evidence of devitalized bone. Chronic osteomyelitis typically is described in patients withinadequate duration of therapy, but patient-specific etiologic and anatomic factors also play a role [48,78].Chronic osteomyelitis is uncommon with current principles of management of acute hematogenousosteomyelitis.

Diagnosis of chronic osteomyelitis requires bone biopsy for culture and histopathologic confirmation.Bone biopsy also may be necessary to exclude other conditions that may have similar radiographicappearance, including nonbacterial osteomyelitis (eg, chronic recurrent multifocal osteomyelitis),Langerhans cell histiocytosis, large cell lymphoma, or primary bone tumors [79]. (See "Hematogenousosteomyelitis in children: Evaluation and diagnosis", section on 'Differential diagnosis'.)

Treatment of chronic osteomyelitis involves removing devitalized bone and long-term administration ofantibiotics [79]. Repeated surgical debridement and bone grafting often are necessary. The importance ofadequate surgical debridement and adequate dosing and duration of, and adherence to, antimicrobialtherapy cannot be overemphasized.

The choice of antimicrobial agents and the duration of therapy have not been well studied [80], largelybecause chronic osteomyelitis is so rare in children. Antibiotic regimens that have been successful insmall case series of patients with methicillin-susceptible S. aureus (MSSA) include oral cloxacillin (notavailable in the United States) combined with probenecid and nafcillin combined with oral rifampin[79,81,82]. In a 2010 systematic review, the success rate for treatment of chronic osteomyelitis due tovarious pathogens (predominantly S. aureus) ranged from 80 to 100 percent with parenteral therapy thatranged from 0.4 to 6 weeks and oral therapy from 0.2 to 4.3 months [80].

We suggest that children with chronic osteomyelitis caused by MSSA be treated with the combination ofrifampin and a beta-lactam antibiotic (eg, penicillin or cephalosporin). For methicillin-resistant S. aureus,treatment with clindamycin is preferred (if the organism is susceptible). For culture-negative cases,treatment as for MSSA may be started, with careful clinical monitoring for improvement.

The duration of therapy is determined on a case-by-case basis. We typically obtain radiographs atmonthly intervals and discontinue therapy after a four-week interval during which all bony changes areindicative of healing (eg, increased bone density, decrease in the size of lytic areas in bone).

Adjunctive measures, such as local irrigation with antimicrobial solutions with or without detergents and







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surgical implantation of beads impregnated with antibiotics, have not been shown conclusively to affectoutcome [83-86].

Complications of chronic osteomyelitis include joint stiffness, limb shortening, and pathologic fractures.(See "Hematogenous osteomyelitis in children: Clinical features and complications", section on'Complications'.)




In children with osteomyelitis, surgical intervention may be required at the time of presentation orduring antimicrobial therapy. Indications for surgical intervention include:

●

Drainage of subperiosteal and soft tissue abscesses and intramedullary purulence•Debridement of contiguous foci of infection•Excision of sequestra (ie, devitalized bone)•Failure to improve after 48 to 72 hours of antimicrobial therapy•

Lesions requiring surgical intervention usually are diagnosed with radiography and magneticresonance imaging (MRI). (See 'Indications for surgery' above.)

For most children with clinical features compatible with osteomyelitis (eg, symptoms and signs ofbone pain, elevated erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP]), we recommendempiric antimicrobial therapy, even if the initial radiograph is normal (Grade 1B). Characteristicfeatures of osteomyelitis are not usually apparent on radiographs until 10 days after symptom onset,and advanced imaging may not be immediately available or feasible. (See 'Indications' above.)

●

Initial antimicrobial therapy for acute hematogenous osteomyelitis usually is administeredparenterally. The empiric regimen is determined by the most likely pathogens and antimicrobialsusceptibilities based on epidemiologic factors including the child's age (table 2), clinical features(table 3), and organisms prevalent in the community (algorithm 1). (See 'Empiric parenteral therapy'above.)

●

For infants <3 months of age, we use a third-generation cephalosporin (eg, cefotaxime[preferred], ceftazidime, ceftriaxone, cefepime), plus an antistaphylococcal agent (usuallyvancomycin or nafcillin/oxacillin). Neonates who have been in an intensive care unit for morethan one week should receive vancomycin rather than nafcillin/oxacillin. (See 'Children younger

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than three months' above.)

For children ≥3 months of age, we use cefazolin, nafcillin/oxacillin, clindamycin, or vancomycin,depending upon the local prevalence of community-associated methicillin-resistantStaphylococcus aureus (CA-MRSA) and the susceptibility of CA-MRSA to clindamycin. (See'Children three months and older' above.)

•

For children ≥3 months of age, it may be necessary to add empiric coverage for pathogensother than S. aureus when clinical or laboratory features suggest a specific pathogen (table 3).(See 'Additional coverage for other pathogens' above.)

•

The antimicrobial regimen can be tailored to a specific pathogen when culture and susceptibilityresults are available (table 6). Children whose cultures remain negative and improve with empirictherapy usually are continued on the same parenteral regimen on which they improved, followed byan oral regimen with a similar spectrum. (See 'Pathogen-directed therapy' above and 'Culture-negative osteomyelitis' above.)

●

Children receiving appropriate antimicrobial therapy generally demonstrate clinical improvementwithin three to four days. Clinical improvement is indicated by decreased fever, pain, erythema,swelling, peripheral white blood cell (WBC) count, and CRP. (See 'Expected response' above.)

●

Lack of improvement or worsening may indicate development of a complication requiring surgicalintervention (eg, abscess, sinus tract, sequestra), thromboembolism, ineffective antimicrobial therapy(eg, unusual or resistant pathogen, polymicrobial infection, insufficient dose), or a diagnosis otherthan osteomyelitis. Additional evaluation may include ESR/CRP, WBC count, plain radiography, andaggressive attempt to isolate fastidious and unusual pathogens. Adjustments to antimicrobial therapymay be necessary. (See 'Lack of improvement or worsening' above.)

●

We administer antimicrobial therapy for a minimum of four weeks. Before discontinuingantimicrobial therapy, we recheck the CRP and the ESR, and we do not stop therapy if either isabnormal. We also generally obtain a radiograph to make sure there are no new bone lesions (eg,abscess, sequestra), even if there is no clinical evidence of treatment failure. (See 'Total duration'above.)

●

Oral antibiotics may be used to complete the course of therapy for acute osteomyelitis in childrenolder than one month who have unequivocal improvement (eg, afebrile for ≥48 hours, decreasedpain and erythema or swelling, normalization of WBC count, consistent decrease in CRP), providedthat (see 'Switch to oral therapy' above):

●

The child is immune competent and fully immunized against Haemophilus influenzae andStreptococcus pneumoniae for age (table 5)

•

The child demonstrates ability to swallow, retain, and absorb an appropriate oral medication•












REFERENCES

1. Kaplan SL. Osteomyelitis in children. Infect Dis Clin North Am 2005; 19:787.

2. Syrogiannopoulos GA, Nelson JD. Duration of antimicrobial therapy for acute suppurativeosteoarticular infections. Lancet 1988; 1:37.

3. Scott RJ, Christofersen MR, Robertson WW Jr, et al. Acute osteomyelitis in children: a review of116 cases. J Pediatr Orthop 1990; 10:649.

4. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch DisChild 2012; 97:545.

5. McNeil JC, Forbes AR, Vallejo JG, et al. Role of Operative or Interventional Radiology-GuidedCultures for Osteomyelitis. Pediatrics 2016; 137.

6. Zhorne DJ, Altobelli ME, Cruz AT. Impact of antibiotic pretreatment on bone biopsy yield forchildren with acute hematogenous osteomyelitis. Hosp Pediatr 2015; 5:337.

7. Le Saux N, Howard A, Barrowman NJ, et al. Shorter courses of parenteral antibiotic therapy do notappear to influence response rates for children with acute hematogenous osteomyelitis: asystematic review. BMC Infect Dis 2002; 2:16.

8. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from30 years of clinical trials? Int J Infect Dis 2005; 9:127.

The clinical course has been uncomplicated, including no progression of bone disease•

If a pathogen is identified, it is susceptible to oral antibiotics•

If cultures are negative, the child has responded as expected to empiric parenteral therapy andthere is an oral regimen with a spectrum similar to the parenteral regimen

•

The patient and family are expected to adhere to the medication and follow-up regimen•

After hospital discharge, children should be evaluated at one- to two-week intervals for clinicalimprovement and complications related to antibiotic therapy (table 7). Monitoring drug levels duringoral therapy may be useful in selected patients (eg, those in whom resolution of clinical findings ornormalization of CRP and ESR does not occur as expected). In addition, a radiograph should beperformed at the end of treatment for children with complicated infections. (See 'Drug monitoring'above.)

●





















9. Howard-Jones AR, Isaacs D. Systematic review of duration and choice of systemic antibiotictherapy for acute haematogenous bacterial osteomyelitis in children. J Paediatr Child Health 2013;49:760.


11. Bradley JS, Wassel RT, Lee L, Nambiar S. Intravenous ceftriaxone and calcium in the neonate:assessing the risk for cardiopulmonary adverse events. Pediatrics 2009; 123:e609.

12. Messina AF, Namtu K, Guild M, et al. Trimethoprim-sulfamethoxazole therapy for children withacute osteomyelitis. Pediatr Infect Dis J 2011; 30:1019.

13. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society ofamerica for the treatment of methicillin-resistant Staphylococcus aureus infections in adults andchildren. Clin Infect Dis 2011; 52:e18.

14. Saavedra-Lozano J, Falup-Pecurariu O, Faust SN, et al. Bone and Joint Infections. Pediatr InfectDis J 2017; 36:788.

15. Lewis JS 2nd, Jorgensen JH. Inducible clindamycin resistance in Staphylococci: should cliniciansand microbiologists be concerned? Clin Infect Dis 2005; 40:280.

16. Frank AL, Marcinak JF, Mangat PD, et al. Clindamycin treatment of methicillin-resistantStaphylococcus aureus infections in children. Pediatr Infect Dis J 2002; 21:530.

17. Chen CJ, Chiu CH, Lin TY, et al. Experience with linezolid therapy in children with osteoarticularinfections. Pediatr Infect Dis J 2007; 26:985.

18. Peltola H, Pääkkönen M, Kallio P, et al. Clindamycin vs. first-generation cephalosporins for acuteosteoarticular infections of childhood--a prospective quasi-randomized controlled trial. Clin MicrobiolInfect 2012; 18:582.

19. de Groot R, Glover D, Clausen C, et al. Bone and joint infections caused by Kingella kingae: sixcases and review of the literature. Rev Infect Dis 1988; 10:998.

20. Goutzmanis JJ, Gonis G, Gilbert GL. Kingella kingae infection in children: ten cases and a review ofthe literature. Pediatr Infect Dis J 1991; 10:677.

21. Yagupsky P, Howard CB, Einhorn M, Dagan R. Kingella kingae osteomyelitis of the calcaneus inyoung children. Pediatr Infect Dis J 1993; 12:540.

22. Kiang KM, Ogunmodede F, Juni BA, et al. Outbreak of osteomyelitis/septic arthritis caused byKingella kingae among child care center attendees. Pediatrics 2005; 116:e206.


































23. Yagupsky P. Antibiotic susceptibility of Kingella kingae isolates from children with skeletal systeminfections. Pediatr Infect Dis J 2012; 31:212.

24. Yagupsky P, Porsch E, St Geme JW 3rd. Kingella kingae: an emerging pathogen in young children.Pediatrics 2011; 127:557.

25. Dubnov-Raz G, Ephros M, Garty BZ, et al. Invasive pediatric Kingella kingae Infections: anationwide collaborative study. Pediatr Infect Dis J 2010; 29:639.

26. Mallet C, Ceroni D, Litzelmann E, et al. Unusually severe cases of Kingella kingae osteoarticularinfections in children. Pediatr Infect Dis J 2014; 33:1.

27. Amit U, Flaishmakher S, Dagan R, et al. Age-Dependent Carriage of Kingella kingae in YoungChildren and Turnover of Colonizing Strains. J Pediatric Infect Dis Soc 2014; 3:160.

28. Basmaci R, Ilharreborde B, Doit C, et al. Two atypical cases of Kingella kingae invasive infectionwith concomitant human rhinovirus infection. J Clin Microbiol 2013; 51:3137.

29. Ruttan TK, Higginbotham E, Higginbotham N, et al. Invasive Kingella kingae Resulting in a BrodieAbscess. J Pediatric Infect Dis Soc 2015; 4:e14.

30. Sadat-Ali M. The status of acute osteomyelitis in sickle cell disease. A 15-year review. Int Surg1998; 83:84.

31. Akakpo-Numado GK, Gnassingbé K, Abalo A, et al. Locations of osteomyelitis in children withsickle-cell disease at Tokoin teaching hospital (Togo). Pediatr Surg Int 2009; 25:723.

32. Boguniewicz J, Rubiano-Landinez A, Lamb G, Kaplan SL. Comparison of musculoskeletal infections due to non-typhoidal Salmonella species and Staphylococcus aureus in immunocompetent children. Abstract and poster presentation, ID Week 2018, San Francisco, CA, October 2018. Available at:https://idsa.confex.com/idsa/2018/webprogram/Paper70569.html (Accessed on January 08, 2019).

33. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease. Report on anational registry of 368 patients. Medicine (Baltimore) 2000; 79:155.

34. Mouas H, Lutsar I, Dupont B, et al. Voriconazole for invasive bone aspergillosis: a worldwideexperience of 20 cases. Clin Infect Dis 2005; 40:1141.



37. Unkila-Kallio L, Kallio MJ, Eskola J, Peltola H. Serum C-reactive protein, erythrocyte sedimentationrate, and white blood cell count in acute hematogenous osteomyelitis of children. Pediatrics 1994;






























93:59.

38. Peltola H, Unkila-Kallio L, Kallio MJ. Simplified treatment of acute staphylococcal osteomyelitis ofchildhood. The Finnish Study Group. Pediatrics 1997; 99:846.

39. Peltola H, Pääkkönen M. Acute osteomyelitis in children. N Engl J Med 2014; 370:352.


41. Roine I, Faingezicht I, Arguedas A, et al. Serial serum C-reactive protein to monitor recovery fromacute hematogenous osteomyelitis in children. Pediatr Infect Dis J 1995; 14:40.

42. Tuason DA, Gheen T, Sun D, et al. Clinical and laboratory parameters associated with multiplesurgeries in children with acute hematogenous osteomyelitis. J Pediatr Orthop 2014; 34:565.

43. Amaro E, Marvi TK, Posey SL, et al. C-Reactive Protein Predicts Risk of VenousThromboembolism in Pediatric Musculoskeletal Infection. J Pediatr Orthop 2019; 39:e62.

44. Courtney PM, Flynn JM, Jaramillo D, et al. Clinical indications for repeat MRI in children with acutehematogenous osteomyelitis. J Pediatr Orthop 2010; 30:883.

45. Yagupsky P. Kingella kingae: from medical rarity to an emerging paediatric pathogen. Lancet InfectDis 2004; 4:358.

46. Centers for Disease Control and Prevention (CDC). Osteomyelitis/septic arthritis caused byKingella kingae among day care attendees--Minnesota, 2003. MMWR Morb Mortal Wkly Rep 2004;53:241.

47. Nelson JD, Bucholz RW, Kusmiesz H, Shelton S. Benefits and risks of sequential parenteral--oralcephalosporin therapy for suppurative bone and joint infections. J Pediatr Orthop 1982; 2:255.

48. Dich VQ, Nelson JD, Haltalin KC. Osteomyelitis in infants and children. A review of 163 cases. AmJ Dis Child 1975; 129:1273.

49. Chou AC, Mahadev A. The Use of C-reactive Protein as a Guide for Transitioning to Oral Antibioticsin Pediatric Osteoarticular Infections. J Pediatr Orthop 2016; 36:173.

50. Nelson JD. Acute osteomyelitis in children. Infect Dis Clin North Am 1990; 4:513.

51. Arnold JC, Cannavino CR, Ross MK, et al. Acute bacterial osteoarticular infections: eight-yearanalysis of C-reactive protein for oral step-down therapy. Pediatrics 2012; 130:e821.

52. Zaoutis T, Localio AR, Leckerman K, et al. Prolonged intravenous therapy versus early transition tooral antimicrobial therapy for acute osteomyelitis in children. Pediatrics 2009; 123:636.

































53. Ruebner R, Keren R, Coffin S, et al. Complications of central venous catheters used for thetreatment of acute hematogenous osteomyelitis. Pediatrics 2006; 117:1210.

54. Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibioticsfor postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr 2015; 169:120.

55. Perkins MD, Edwards KM, Heller RM, Green NE. Neonatal group B streptococcal osteomyelitis andsuppurative arthritis. Outpatient therapy. Clin Pediatr (Phila) 1989; 28:229.

56. Schwartz GJ, Hegyi T, Spitzer A. Subtherapeutic dicloxacillin levels in a neonate: possiblemechanisms. J Pediatr 1976; 89:310.

57. Maraqa NF, Gomez MM, Rathore MH. Outpatient parenteral antimicrobial therapy in osteoarticularinfections in children. J Pediatr Orthop 2002; 22:506.

58. Bryson YJ, Connor JD, LeClerc M, Giammona ST. High-dose oral dicloxacillin treatment of acutestaphylococcal osteomyelitis in children. J Pediatr 1979; 94:673.

59. Martínez-Aguilar G, Hammerman WA, Mason EO Jr, Kaplan SL. Clindamycin treatment of invasiveinfections caused by community-acquired, methicillin-resistant and methicillin-susceptibleStaphylococcus aureus in children. Pediatr Infect Dis J 2003; 22:593.

60. Landersdorfer CB, Bulitta JB, Kinzig M, et al. Penetration of antibacterials into bone:pharmacokinetic, pharmacodynamic and bioanalytical considerations. Clin Pharmacokinet 2009;48:89.

61. Nelson JD. Toward simple but safe management of osteomyelitis. Pediatrics 1997; 99:883.

62. Belthur MV, Phillips WA, Kaplan SL, Weinberg J. Prospective evaluation of a shortened regimen oftreatment for acute osteomyelitis and septic arthritis in children. J Pediatr Orthop 2010; 30:942.

63. Peltola H, Pääkkönen M, Kallio P, et al. Short- versus long-term antimicrobial treatment for acutehematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positivecases. Pediatr Infect Dis J 2010; 29:1123.

64. HARRIS NH. Some problems in the diagnosis and treatment of acute osteomyelitis. J Bone JointSurg Br 1960; 42-B:535.

65. Blockey NJ, Watson JT. Acute osteomyelitis in children. J Bone Joint Surg Br 1970; 52:77.

66. Al-Homaidhi H, Abdel-Haq NM, El-Baba M, Asmar BI. Severe hepatitis associated with oxacillintherapy. South Med J 2002; 95:650.

67. Olson SC, Smith S, Weissman SJ, Kronman MP. Adverse Events in Pediatric Patients ReceivingLong-Term Outpatient Antimicrobials. J Pediatric Infect Dis Soc 2015; 4:119.


































68. Murphy JL, Fenn N, Pyle L, et al. Adverse Events in Pediatric Patients Receiving Long-term Oraland Intravenous Antibiotics. Hosp Pediatr 2016; 6:330.

69. Marshall GS, Mudido P, Rabalais GP, Adams G. Organism isolation and serum bactericidal titers inoral antibiotic therapy for pediatric osteomyelitis. South Med J 1996; 89:68.

70. Belthur MV, Birchansky SB, Verdugo AA, et al. Pathologic fractures in children with acuteStaphylococcus aureus osteomyelitis. J Bone Joint Surg Am 2012; 94:34.

71. Karwowska A, Davies HD, Jadavji T. Epidemiology and outcome of osteomyelitis in the era ofsequential intravenous-oral therapy. Pediatr Infect Dis J 1998; 17:1021.

72. Yeo A, Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ 2014; 348:g66.

73. Edwards MS, Baker CJ, Wagner ML, et al. An etiologic shift in infantile osteomyelitis: theemergence of the group B streptococcus. J Pediatr 1978; 93:578.

74. Memon IA, Jacobs NM, Yeh TF, Lilien LD. Group B streptococcal osteomyelitis and septic arthritis.Its occurrence in infants less than 2 months old. Am J Dis Child 1979; 133:921.

75. Peters W, Irving J, Letts M. Long-term effects of neonatal bone and joint infection on adjacentgrowth plates. J Pediatr Orthop 1992; 12:806.

76. Williamson JB, Galasko CS, Robinson MJ. Outcome after acute osteomyelitis in preterm infants.Arch Dis Child 1990; 65:1060.

77. Overturf GD. Bacterial infections of the bone and joints. In: Infectious Diseases of the Fetus and Newborn, 7th ed, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.296.

78. Riise ØR, Kirkhus E, Handeland KS, et al. Childhood osteomyelitis-incidence and differentiationfrom other acute onset musculoskeletal features in a population-based study. BMC Pediatr 2008;8:45.


80. Howard-Jones AR, Isaacs D. Systematic review of systemic antibiotic treatment for children withchronic and sub-acute pyogenic osteomyelitis. J Paediatr Child Health 2010; 46:736.

81. Bell SM. Further observations on the value of oral penicillins in chronic staphylococcalosteomyelitis. Med J Aust 1976; 2:591.

82. Norden CW, Bryant R, Palmer D, et al. Chronic osteomyelitis caused by Staphylococcus aureus:controlled clinical trial of nafcillin therapy and nafcillin-rifampin therapy. South Med J 1986; 79:947.






























83. Makin M, Geller R, Jacobs J, Sacks T. Non-toxic detergent irrigation of chronic infections. Anexperimental evaluation. Clin Orthop Relat Res 1973; :320.

84. Anderson LD, Horn LG. Irrigation-suction technic in the treatment of acute hematogenousosteomyelitis, chronic osteomyelitis, and acute and chronic joint infections. South Med J 1970;63:745.

85. Blaha JD, Calhoun JH, Nelson CL, et al. Comparison of the clinical efficacy and tolerance ofgentamicin PMMA beads on surgical wire versus combined and systemic therapy for osteomyelitis.Clin Orthop Relat Res 1993; :8.

86. Walenkamp GH, Kleijn LL, de Leeuw M. Osteomyelitis treated with gentamicin-PMMA beads: 100patients followed for 1-12 years. Acta Orthop Scand 1998; 69:518.














GRAPHICS


Imagingmodality

Abnormal findings











Computedtomography


Cortex destruction













¶



Most common causes of bacterial osteomyelitis in children according to age

Age group Most common bacterial etiologies

<3 months Staphylococcus aureus (MSSA and MRSA)

Group B Streptococcus (Streptococcus agalactiae)

Gram-negative bacilli

3 months to earlychildhood

S. aureus (MSSA and MRSA)

Group A Streptococcus (Streptococcus pyogenes)

Streptococcus pneumoniae

Kingella kingae*

Hib

Older children andadolescents

S. aureus (MSSA and MRSA)

Group A Streptococcus (S. pyogenes)

S. pneumoniae

MSSA: methicillin-susceptible S. aureus; MRSA: methicillin-resistant S. aureus; Haemophilus influenzae type b: Hib.* Usually 36 months of age or less.¶ In children incompletely immunized against Hib.


¶




Clinical features

























Our approach to empiric antimicrobial therapy for children with acute hematogenous osteomy

This algorithm is intended for use with UpToDate content on management of osteomyelitis in children. Refer to UpToDate c additional aspects of management, including indications for surgical intervention.

ICU: intensive care unit; MRSA: methicillin-resistant S. aureus; Hib: Haemophilus influenzae type b; GI: gastrointestinal; MSSA: meth * Ceftriaxone is contraindicated in infants ≤28 days if they require or are expected to require treatment with intravenous solutions co ¶ Some experts also include cefazolin as an antistaphylococcal agent for infants age 1 to 3 months in whom central nervous system in Δ At some institutions, clindamycin is used as an alternative to vancomycin if <10% of S. aureus isolates are MRSA and the infant has ◊ Alternatives to vancomycin or clindamycin when MRSA is a concern include linezolid or daptomycin (daptomycin only if the child is ≥involvement).



§ For children with life-threatening infections, the combination of vancomycin plus either nafcillin or oxacillin provides antibactericidal ¥ Consultation with an infectious disease specialist may be warranted for immunocompromised patients (eg, sickle cell disease, chron with unusual pathogens or resistance profiles.‡ We consider the prevalence of MRSA in the community to be increased if ≥10% of S. aureus isolates are MRSA; other experts may † We consider the prevalence of clindamycin-resistant MRSA to be increased if ≥10% of MRSA isolates are resistant to clindamycin (c threshold.** Refer to UpToDate content on prevention of Hib infection for details.


¶

Δ



Suggested doses of parenteral antibiotics commonly used in the treatment ofosteoarticular infections in infants and children

Intravenousagent

Dose for infants 8 to 28 days of age Dose for children >28 days of age

Ampicillin 150 mg/kg per day divided in 2 doses 200 to 400 mg/kg per day divided in 4 doses;maximum dose 12 g/day

Cefazolin 100 to 150 mg/kg per day divided in 3 doses 100 to 150 mg/kg per day divided in 3 doses;maximum dose 6 g/day

Cefepime 60 to 100 mg/kg per day divided in 2 doses 100 to 150 mg/kg per day divided in 3 doses;maximum dose 6 g/day

Cefotaxime 150 to 200 mg/kg per day divided in 3 doses 150 to 200 mg/kg per day divided in 3 or 4doses; maximum dose 8 g/day

Ceftazidime 150 mg/kg per day divided in 3 doses 125 to 150 mg/kg per day divided in 3 doses;maximum daily dose 6 g

Ceftriaxone 50 to 75 mg/kg per day in 1 dose 75 to 100 mg/kg per day divided in 1 or 2doses; maximum dose 4 g/day

Clindamycin 20 to 30 mg/kg per day divided in 3 doses 25 to 40* mg/kg per day divided in 3 or 4doses; maximum dose 2.7 g/day

Daptomycin NA 1 through 6 years: 12 mg/kg per day in 1 dose

7 through 11 years: 9 mg/kg per day in 1 dose

12 through 17 years: 7 mg/kg per day in 1dose

Gentamicin 7.5 mg/kg per day divided in 3 doses 7.5 mg/kg per day divided in 3 doses

Linezolid 30 mg/kg per day divided in 3 doses <12 years: 30 mg/kg per day in 3 doses

≥12 years: 600 mg twice per day

Nafcillin 100 mg/kg per day divided in 4 doses 150 to 200 mg/kg per day divided in 4 doses;maximum dose 12 g/day

Oxacillin 100 mg/kg per day divided in 4 doses 150 to 200 mg/kg per day divided in 4 to 6doses; maximum dose 12 g/day

Penicillin 150,000 units/kg per day divided in 3 doses 250,000 to 400,000 units/kg per day divided in4 to 6 doses; maximum dose 24 million unitsper day

Vancomycin Loading dose of 20 mg/kg followed bymaintenance dose according to serumcreatinine as follows:

<0.7 mg/dL: 15 mg/kg every 12 hours0.7 to 0.9 mg/dL: 20 mg/kg every 24hours1.0 to 1.2 mg/dL: 15 mg/kg every 24hours1.3 to 1.6 mg/dL: 10 mg/kg every 24hours>1.6 mg/dL: 15 mg/kg every 48 hours

45 to 60 mg/kg per day divided in 3 to4 doses; maximum dose 4 g/day

Refer to UpToDate topics on management of osteomyelitis and septic arthritis in children for details regardingindications for particular drugs; recommended doses are for patients with normal renal function and infants born at>34 weeks' gestation. Consultation with an expert in pediatric infectious diseases is suggested for infants born at ≤34weeks gestation.

NA: not available; IV: intravenous.*40 mg/kg per day is preferred for children ≥3 months of age.¶ Daptomycin should not be used in children with concomitant pulmonary involvement and is not recommended in children <1year of age because of the risk of potential effects on muscular, neuromuscular, and/or nervous systems (peripheral and/orcentral) observed in dogs. It is not approved for the treatment of osteoarticular infections in children; the appropriate dose for

¶

Δ



osteoarticular infections has not yet been established but is the subject of clinical trials. The doses provided above are those thatare recommended for Staphylococcus aureus bacteremia in children.Δ Dosing algorithm for vancomycin based upon serum creatinine concentration in neonates born at gestational age >28 weeks.A vancomycin dosing method based upon postnatal age and weight is provided as an alternative to the serum creatinine-basedmethod listed above and may be useful in some clinical situations. This particular algorithm was provided in the 2009 edition ofthe Red Book.Postnatal age <7 days:

<1200 g: 15 mg/kg IV every 24 hours1200 to 2000 g: 10 to 15 mg/kg IV every 12 or 18 hours>1200 g: 10 to 15 mg/kg IV every 8 or 12 hours

Postnatal age ≥7 days: <1200 g: 15 mg/kg IV every 24 hours1200 to 2000 g: 10 to 15 mg/kg IV every 8 or 12 hours>2000 g: 10 to 15 mg/kg IV every 6 or 8 hours

Data from:1. American Academy of Pediatrics. Antibacterial drugs for newborn infants: Dose and frequency of administration. In: Red

Book: 2009 Report of the Committee on Infectious Diseases, 28 ed, Pickering LK (Ed), American Academy of Pediatrics,Elk Grove Village, IL 2009. p.745.

2. American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book: 2018 Report of the Committee onInfectious Diseases, 31 ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics,Itasca, IL 2018. p.914.

3. Cubicin (daptomycin for injection). United States Prescribing Information. Revised September, 2017. US Food and DrugAdministration. Available online at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (accessed August 3,2018).


[1]

th

st

¶

Δ

◊

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm



Suggested criteria for full Haemophilus influenza type b and Streptococcus pneumoniaeimmunization status when considering empiric antibiotics for community-acquiredpneumonia in children

Current age* Criteria for full immunization

Haemophilus influenzae type b

12 to 15 months ≥2 doses of Hib conjugate vaccine, with at least one dose at≥12 months of age

15 months to 5 years ≥2 doses of Hib conjugate vaccine, with at least one dose at≥12 months of age, or

≥1 dose of Hib conjugate vaccine at ≥15 months of age

≥5 years, not high risk Hib immunization not necessary

Streptococcus pneumoniae

12 to 24 months ≥3 doses of PCV at <16 months, with ≥1 dose at ≥12months, or

2 doses of PCV, both at ≥12 months

24 months through 5 years ≥3 doses of PCV at <16 months, with ≥1 dose at ≥12months, or

2 doses of PCV, both at ≥12 months, or

≥1 dose of PCV at ≥24 months

>5 years, not high risk PCV immunization not necessary

Hib: H. influenzae type b; PCV: pneumococcal conjugate vaccine.* Children younger than 12 months are incompletely immunized against Hib and S. pneumoniae.¶ Immunizations must be completed at least two weeks before pneumonia diagnosis.Δ Children at high risk for invasive Hib disease include chemotherapy recipients and those with anatomic or functional asplenia(including sickle cell disease), HIV infection, immunoglobulin deficiency, or early component complement deficiency. Please referto the UpToDate topic on prevention of H. influenzae infection for a discussion of full Hib immunization in children at high risk forinvasive Hib disease.◊ Children at high risk for invasive S. pneumoniae disease include those with chronic heart disease (particularly cyanoticcongenital heart disease and cardiac failure); chronic lung disease (including asthma if treated with high-dose oral corticosteroidtherapy); diabetes mellitus; cerebrospinal fluid leak; cochlear implant; sickle cell disease and other hemoglobinopathies;anatomic or functional asplenia; HIV infection; chronic renal failure; nephrotic syndrome; diseases associated with treatmentwith immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, and Hodgkindisease; solid organ transplantation; or congenital immunodeficiency. Please refer to the UpToDate topics on PCVs andpneumococcal polysaccharide vaccines for a discussion of full S. pneumoniae immunization in children at high risk for invasive S.pneumoniae disease.


¶

Δ

◊



Suggested antimicrobial regimens for the most commonly isolated pathogens causingosteoarticular infections in infants and children when results of culture and susceptibilitytesting are known

PathogenParenteral

agentsOral agents

Staphylococcus aureus

Methicillin-susceptible Cefazolin

Nafcillin

Oxacillin

Cephalexin

Cloxacillin (not available in the UnitedStates)

Dicloxacillin

Clindamycin*

Methicillin-resistant

Clindamycin-susceptible Vancomycin

Clindamycin

Clindamycin

Clindamycin-resistant Vancomycin

Linezolid

Daptomycin

Linezolid

Streptococcus agalactiae (Group BStreptococcus)

Penicillin Oral therapy not suggested in infants

Streptococcus pyogenes (Group AStreptococcus)

Penicillin

Ampicillin

Penicillin

Amoxicillin

Streptococcus pneumoniae (Pneumococcus)

Penicillin-susceptible Penicillin Penicillin

Amoxicillin

Penicillin-nonsusceptible Cefotaxime

Ceftriaxone

Clindamycin*

Linezolid

Clindamycin*

Linezolid

Kingella kingae Penicillin

Cefazolin

Cefotaxime

Ceftriaxone

Penicillin

Cephalexin

Cefixime

Haemophilus influenzae type b Cefotaxime

Ceftriaxone

Cefuroxime

Amoxicillin (if susceptible)

Cefixime

* If isolate is clindamycin-susceptible.¶ Clindamycin should not be used even if D-test is negative.Δ Daptomycin should not be used in children with concomitant pulmonary involvement. It is not approved for the treatment ofosteoarticular infections in children; the appropriate dose has not been established.


¶

Δ



Our approach to monitoring response to treatment and adverse effects of therapy forosteomyelitis in children and adolescents

When to perform Comments

Clinical evaluation:TemperaturePain and rangeof movementLocalizedswelling orerythema

At least daily during admissionEvery 1 to 2 weeks after discharge

Worsening or failure to improve mayindicate:

Development of a complicationUnusual or resistant pathogenPolymicrobial infectionInadequate dose of antimicrobial agent,or failure to administer itA diagnosis other than osteomyelitis

CRP and ESR CRP: During admission:Every 2 to 3 days until ≥50% reductionor steady decline has occurred, thenweekly if child remains hospitalizedIf clinical status worsensWeekly during outpatient follow-up

ESR: On admission and before stoppingantimicrobial therapy*

Highly elevated CRP after ≥4 days oftreatment may be associated with prolongedsymptoms of progression of radiographicchangesESR is usually at its highest 2 to 3 days afterbeginning antimicrobial therapy and declinesslowlyWe continue antibiotic therapy for 4 weeksor until CRP and ESR are normal, whicheveris longer*

CBC with differential Before switch to oral therapy if WBC count iselevated at time of diagnosis

The WBC count is elevated at diagnosis inapproximately one-third of children withosteomyelitisIt usually normalizes within 7 to 10 days ofinitiation of effective antimicrobial therapy

Weekly in children receiving beta-lactamantibiotics (eg, penicillins, cephalosporins)Weekly for in children receiving linezolid for>2 weeks

Adverse effects of beta-lactam drugs andlinezolid include pancytopenia andleukopenia

Serum antibioticconcentrations

May be useful if poor absorption of antibioticor failure to administer it are suspected

Rare patients have inadequate serumconcentrations despite high doses ofantimicrobials

Biochemical profile(including serumaminotransferases)

Weekly if the patient is receiving penicillinantibiotics or intravenous cephalosporins

Adverse effects of beta-lactam drugs includeimpaired liver or renal function, andantibiotic-associated diarrhea

Radiographs If the clinical status worsens or fails toimprove

To assess complications:Soft tissue, subperiosteal, orintramedullary abscessSinus tractSequestraPathologic fracture

Additional imaging, usually with MRI, maybe necessary

Before discontinuation of antimicrobialtherapy

To ensure that there are no new bonelesions (eg, devitalized bone, lytic lesions)

CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; CBC: complete blood count; WBC: white blood cell; MRI:magnetic resonance imaging; MRSA: methicillin-resistant Staphylococcus aureus.* Some experts do not use normalization of ESR as a criterion for discontinuation of antimicrobial therapy or may documentnormalization of ESR only in children with osteomyelitis caused by MRSA and in cases that have been initially complicated (eg,concomitant septic arthritis, intraosseous or periosteal abscess or lytic bone lesions at presentation, requiring repeated surgicalmanagement of soft tissue foci, delayed normalization of CRP beyond the expected 7 to 10 days).¶ Some experts also obtain monitoring every 1 to 2 weeks in children receiving clindamycin, although the risk of adversehematologic effects is lower than with beta-lactam antibiotics.

¶

Δ



Δ Expert opinion regarding monitoring of serum antibiotic concentrations varies. Some experts monitor serum concentrationsonly in children receiving oral therapy in whom CRP (and ESR, if measured) fails to normalize.


¶

Δ

◊

§



Doses of oral antibiotics commonly used in the treatment of osteoarticular infections ininfants and children >1 month of age*

Oral agent Dose

Amoxicillin 100 mg/kg per day divided in 4 doses; maximum dose 4 g/day

Cefixime 8 mg/kg per day divided in 1 or 2 doses; maximum dose 400 mg/day

Cephalexin 100 to 150 mg/kg per day divided in 3 or 4 doses; maximum dose 4 g/day

Clindamycin 30 to 40 mg/kg per day divided in 3 doses; maximum dose 2.7 g/day

Cloxacillin 125 mg/kg per day divided in 4 doses; maximum dose 4 g/day

Dicloxacillin 100 mg/kg per day divided in 4 doses; maximum dose 4 g/day

Linezolid <12 years: 30 mg/kg per day divided in 3 doses; maximum dose 1.8 g/day

≥12 years: 600 mg twice per day

Penicillin V 150 mg/kg per day divided in 6 doses; maximum dose 2 g/day

* Refer to UpToDate topics on treatment of bacterial arthritis and osteomyelitis in children for details regarding indications forparticular drugs.¶ Recommended doses are for patients with normal renal function. Beta-lactam antibiotics administered orally for osteoarticularinfections generally are given in higher doses than those used for treatment of other infections and recommended in packageinserts.Δ 40 mg/kg per day is preferred for children ≥3 months. ◊ Cloxacillin is not available in the United States.§ Dicloxacillin suspension is no longer available.


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Δ

◊

§



Developmental pathogenesis of acute osteomyelitis

(A) In newborns, infection commonly spreads along the subperiosteal space andruptures through the cortex into soft tissue or adjacent joint spaces.(B and C) In infants and older children, capillaries do not cross the physis.Infection in older children is generally confined to the metaphysis, and thethicker cortex and denser periosteum limit spread to soft tissues.





Hematogenous osteomyelitis in children: Clinical features and complications - UpToDate



Hematogenous osteomyelitis in children: Clinical features andcomplicationsAuthor: Paul Krogstad, MD Section Editors: Sheldon L Kaplan, MD, William A Phillips, MD Deputy Editor: Mary M Torchia,MD



INTRODUCTION

The clinical features and complications of hematogenous osteomyelitis in children will be discussed here.The epidemiology, microbiology, evaluation, diagnosis, and management of osteomyelitis in children arediscussed separately:

TERMINOLOGY

Osteomyelitis is an infection localized to bone. It is usually caused by microorganisms (predominantlybacteria) that enter the bone hematogenously.

Pathogenic mechanisms for nonhematogenous osteomyelitis include direct inoculation (usually traumatic,but also surgical) and local invasion from a contiguous infection (eg, cellulitis, decubitus ulcer, sinusitis,periodontal disease). Risk factors for nonhematogenous osteomyelitis include open fractures that requiresurgical reduction, implanted orthopedic hardware (such as pins or screws), bite wounds, and puncturewounds. (See "Infectious complications of puncture wounds".)

CLINICAL FEATURES

Clinical presentation — The initial symptoms of hematogenous osteomyelitis can be nonspecific inchildren of all ages (eg, malaise, low-grade fever). Once the infection becomes established in bone,symptoms are more localized.

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Children with hematogenous osteomyelitis usually present acutely with fever, constitutional symptoms(eg, irritability, decreased appetite or activity), focal findings of bone inflammation (warmth, swelling, pointtenderness), and limitation of function (eg, limp, limited use of extremity) [1].

In a 2012 systematic review that included more than 12,000 children with acute and subacuteosteomyelitis, presenting features included [2]:

Clinical features by age group — The clinical features of osteomyelitis are influenced by thecharacteristics of the developing skeleton. (See "Hematogenous osteomyelitis in children: Epidemiology,pathogenesis, and microbiology", section on 'Pathogenesis'.)

Birth to three months — Osteomyelitis is rare in newborns and young infants without underlying riskfactors (eg, prematurity, skin infection, complicated delivery) [3,4]. Approximately one-half of cases areassociated with antecedent infections, which often are health care-associated [5]. (See "Hematogenousosteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Risk factors'.)

Symptoms of osteomyelitis in young infants may be mild and nonspecific [4]. Many infants lack focalfindings, are afebrile, and continue to feed well, although they may have vomiting and irritability. Systemicsymptoms may be more pronounced with Staphylococcus aureus osteomyelitis than with osteomyelitiscaused by other pathogens. S. aureus osteomyelitis also may be associated with multifocal infection [5-7].

Common initial signs include decreased movement, swelling, and/or erythema of the affected area. Asthe infection progresses, the epiphysis and adjacent joint may become involved. Soft tissue surroundingthe infected bone may become swollen and discolored as purulence ruptures through the thin bonycortex into the contiguous muscle bed. (See "Hematogenous osteomyelitis in children: Epidemiology,pathogenesis, and microbiology", section on 'Birth to three months'.)

In a series of 30 infants (<4 months) with confirmed osteomyelitis, only 10 were febrile; five had no focalfindings and were evaluated for osteomyelitis because of positive blood culture or suspected sepsis [4].Concomitant septic arthritis occurred in 14 (42 percent) and multifocal infection in 12 (40 percent).

Older infants and toddlers — The initial symptoms of hematogenous osteomyelitis in older infantsand young children frequently are nonspecific and mild. Verbal children may complain of localized pain. Ahistory of nonspecific trauma may precede the onset of symptoms; diagnosis may be delayed ifmusculoskeletal complaints are initially attributed to trauma.

Pain – 81 percent●

Localized signs/symptoms – 70 percent●

Fever – 62 percent●

Reduced range of movement – 50 percent●

Reduced weight-bearing – 50 percent●

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As the infection progresses, the child may refuse to use the affected extremity. Ambulatory youngchildren with osteomyelitis of the lower extremity, pelvis, or spine may develop a progressive limp orrefuse to sit, walk, or bear weight. Nonambulatory young children may refuse to sit or crawl, becomeirritable when picked up, or appear to be in pain or uncomfortable with diaper changing.

On examination, pain is typically well localized, with point tenderness over the infected bone; there maybe contiguous edema. Pain is referred to the involved area when other parts of the long bone arepercussed. In older infants and young children with vertebral osteomyelitis, there may be percussiontenderness over the contiguous spine, hip pain and stiffness, or loss of lumbar lordosis. However, it maybe difficult to elicit these findings. Pelvic osteomyelitis may be localized to the buttock. In children withdiscitis, compression of the spine occasionally produces pain at the infected disc.

Older children and adolescents — In late childhood and adolescence, patients are more likely thanyounger children to complain of localized pain. Injury, rather than infection, may be suspected initially,particularly if the child is without fever and systemic symptoms, and may delay the diagnosis ofosteomyelitis.

On physical examination, the infectious process is more anatomically confined than in younger children.There is less swelling of the surrounding soft tissue and less functional restriction. The point tendernessis more circumscribed, though pain is still referred to the involved area when other parts of the long boneare percussed. In older children and adolescents with vertebral osteomyelitis, there may be percussiontenderness over the contiguous spine, hip pain and stiffness, or loss of lumbar lordosis.

Severe staphylococcal sepsis and venous thrombosis have been described in some adolescents withosteomyelitis [8,9] (see 'Complications' below). However, adolescents with subacute/chronicosteomyelitis may have developed a localized, sclerotic, intraosseous abscess (Brodie abscess (image1)) and typically present with insidious onset of mild to moderate long bone pain, with or without fever[10].

Site of infection — Hematogenous osteomyelitis generally occurs at only one site [1]. However,multifocal infection may occur, particularly in critically ill neonates and children with disease caused bycommunity-associated methicillin-resistant S. aureus (CA-MRSA) or Bartonella henselae, or in childrenwith sickle cell disease [4,8,11-13].

Long (tubular) bones are affected more frequently than nontubular bones (ie, flat, irregular, and sesamoidbones) (figure 1). Infection in nontubular bones occurs most often in the calcaneus and pelvis [2]. (See'Chronic hemodialysis' below and "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis,and microbiology", section on 'Microbiology'.)

Long (tubular) bones — More than 80 percent of cases of hematogenous osteomyelitis occur in thelong (tubular) bones, usually originating in the metaphyses [2,14]. The femur and tibia are mostfrequently involved (figure 1).

Because the long bones are affected in the majority of cases, the clinical features of long-bone






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osteomyelitis are the "classic" presentation: focal findings of bone inflammation (warmth, swelling, pointtenderness) and limitation of function (eg, limp, limited use of extremity) [15]. (See 'Clinical presentation'above.)

Spine — Infections of the spine can involve either the vertebral bodies or the intervertebral discs.Osteomyelitis of the spine should prompt consideration of Bartonella henselae and other unusualpathogens. (See 'Pathogen-specific features' below.)

Vertebral bodies — The vertebrae are involved in approximately 4 percent of cases ofosteomyelitis in children [2,16]. Patients usually are older than eight years. They seek medical attentionbecause of dull, constant back pain. They may appear toxic and markedly febrile after an indolent coursewith low-grade fever for two weeks' to several months' duration. Examination findings of vertebralosteomyelitis may include exquisite tenderness with percussion of the spinal dorsal process, spasm ofthe paraspinous muscles around the involved vertebrae, and pain with flexion or extension of the spine.

In a retrospective case series of 14 children with vertebral osteomyelitis, the mean age was 7.5 yearsand the mean duration of symptoms was 33 days [16]. At the time of initial presentation, 8 of the 14complained of back pain, and 11 were febrile.

Vertebral osteomyelitis is rare in newborns and is difficult to diagnose. Although some infants may behighly febrile and toxic-appearing, most have nonspecific symptoms and signs that are often overlooked,even in closely monitored settings such as neonatal intensive care units [17]. The infant may eventuallydevelop irritability when moved or have signs of infection at another site. Given the indolent presentation,vertebral osteomyelitis in newborns may be complicated by paraspinal abscess or collapse of one ormore vertebral bodies, with secondary kyphosis or paralysis [17-19]. (See 'Complications' below.)

Intervertebral discs — Vertebral infections in children younger than five usually involve theintervertebral disc (discitis) rather than the vertebral body [16]. Discitis occurs almost exclusively in thelumbar regions. In young children, discitis typically presents with the gradual onset of irritability and backpain, limp, or refusal to crawl or walk, without systemic toxicity; fever usually is absent or low grade[16,20-22]. Abdominal pain and/or vomiting (secondary to ileus) may be the only complaints in childrenwith involvement of T8 to L1. Most patients have had symptoms for three weeks or longer by the timediscitis is diagnosed [16,20,23]. Examination findings may include percussion tenderness over theinvolved spine, hip pain and stiffness, loss of lumbar lordosis, neurologic findings (decreased musclestrength or reflexes), and ileus (with lesions of T8 to L1).

In a retrospective case series of 36 children with discitis, the mean age was 2.8 years and the meanduration of symptoms was 22 days [16]. At the time of presentation, 10 of the 36 were febrile, 23 of the27 children <3 years of age had a limp or problems walking (eg, unsteady gait, refusal to walk, refusal tobear weight), and 6 of the 9 children ≥3 years of age complained of back pain.

Pelvis — Children with pelvic osteomyelitis often have symptoms referable to the hip, such as a gaitabnormality or hip pain [24-26]. However, they also may localize the pain to the thigh, abdomen, lumbar







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spine, or buttocks. Fever is frequently absent. Osteomyelitis of the pelvis is generally caused by S.aureus and other gram-positive pathogens, but unusual organisms (including Salmonella species and B.henselae) should be considered [26,27]. (See 'Pathogen-specific features' below.)

Unlike children with septic arthritis of the hip, children with pelvic osteomyelitis usually allow passiverange of motion of the hip (which may be decreased). However, pain may be elicited by simultaneouslyputting the hip in flexion, abduction, and external rotation (figure 2). In addition, careful palpation andrectal examination may reveal areas of point tenderness [27].

The clinical features of pelvic osteomyelitis were described in a case series of 64 children from a singleinstitution [26]:

Similar findings were reported in a smaller case series and literature review [25].

Pathogen-specific features — The clinical features may vary depending upon the causative organism(table 1):

The average age was 11.5 years (range 1.2 to 17.5 years)●

Presenting symptoms included pain (95 percent), fever (47 percent), and altered weight-bearing (48percent)

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The average duration of complaints was 13 days●

Examination findings included tenderness in 66 percent, fever in 39 percent, and decreased range ofmotion at the hip in 43 percent

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White blood cell (WBC) count was >12,000/microL in 30 percent (average 15,800/microL) anderythrocyte sedimentation rate was increased in 88 percent (average 44 mm/h)

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The ilium was involved most frequently●

In neonates, S. aureus osteomyelitis frequently is associated with systemic symptoms and multifocalinfection. In contrast, group B Streptococcus usually affects a single bone without a clinically evidentpreceding infection.

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Osteomyelitis caused by CA-MRSA is more severe than osteomyelitis caused by other pathogens(eg, increased height and duration of fever, greater elevation of inflammatory markers, increased riskof complications, increased need for surgical intervention) [8,9,28-31].

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Panton-Valentine leukocidin (PVL)-positive isolates of S. aureus are associated with severe localizedreaction and systemic inflammatory response (eg, greater elevation of inflammatory markers,increased frequency of bone destruction, increased need for surgical intervention) [28-31]. Thespecific role of PVL in the pathogenesis of osteomyelitis remains unclear; it may be a surrogate forother virulence factors [32].

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Special populations

Hemoglobinopathy — The clinical manifestations of hematogenous osteomyelitis in children withhemoglobinopathy (hemoglobin SS, S-beta thalassemia, hemoglobin SO-Arab, and certain children withhemoglobin SC) are similar to those in children without hemoglobinopathy. However, multiple sites maybe involved, and it can be difficult to distinguish osteomyelitis from a vaso-occlusive crisis [40,41]. (See'Clinical features' above and "Overview of variant sickle cell syndromes" and "Acute and chronic bonecomplications of sickle cell disease", section on 'Osteomyelitis and septic arthritis'.)

Chronic granulomatous disease — The clinical manifestations of osteomyelitis in children withchronic granulomatous disease may be minimal, even with well-established destructive lesions. Theyalso may have recurrent episodes of osteomyelitis caused by bacterial and fungal pathogens. (See"Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on'Infections'.)

Chronic hemodialysis — Children undergoing chronic hemodialysis are at greater risk forhematogenous osteomyelitis because of repeated invasions of their vascular compartment [42].Indwelling intravenous cannulas can be colonized with coagulase-negative staphylococci or S. aureus,and osteomyelitis may develop. The thoracic spine and ribs are the bones most commonly involved;other tubular and cuboidal bones that have been traumatized also can become infected.

Central venous catheters — Rare cases of osteomyelitis have been described in children with

Osteomyelitis caused by group A Streptococcus is associated with higher fever (38.9°C [102°F])than methicillin-susceptible S. aureus (38.1°C [100.6°F]) or pneumococcus (38.2°C [100.8°F]) [2].

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Kingella kingae osteomyelitis generally affects children between 6 and 36 months of age and istypically milder and more indolent than osteomyelitis due to other pathogens. In one series of 43children with K. kingae osteoarticular infections, only 15 percent of children were febrile atpresentation, and 39 percent had normal inflammatory markers [33]. K. kingae maydisproportionately affect nontubular bones (eg, sternum, vertebrae, calcaneum) [34].

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B. henselae is a well-documented cause of osteomyelitis of the axial skeleton (skull, vertebralbodies, ribs, and pelvis) after a cat scratch or bite (although contact with cats may not be specificallyrecalled in proven cases); it also may cause multifocal disease [13,35,36].

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Compared with osteomyelitis cases in which an organism is not identified, culture-positiveosteomyelitis is more frequently associated with a history of antecedent trauma; erythema, swelling,or frank cellulitis overlying the infected bone; a shorter duration of symptoms; and a higher WBCcount [37,38].

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Coccidioidomycosis (an endemic mycosis due to Coccidioides immitis or Coccidioides posadasii) isa well-known cause of osteomyelitis in the southwestern United States; polyostotic disease iscommon, and the axial skeleton is frequently involved [39].

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intestinal failure who are reliant upon indwelling central venous catheters and total parenteral nutrition.Osteomyelitis should be suspected when there are signs and symptoms of musculoskeletal infection [43].

LABORATORY FEATURES

The laboratory findings of children with osteomyelitis are described below. The laboratory evaluation forchildren with suspected osteomyelitis is discussed separately. (See "Hematogenous osteomyelitis inchildren: Evaluation and diagnosis", section on 'Initial evaluation'.)

RADIOGRAPHIC FEATURES

The radiographic features of osteomyelitis depend upon the imaging modality (table 2) [54]. Indications

White blood cell count – Elevations in the peripheral white blood cell count (WBC) count inosteomyelitis are variable and nonspecific [44]. In a 2012 systematic review that included >12,000patients, WBC count was elevated in only 36 percent of children at the time of presentation andnormalized rapidly [2]. In a prospective study of 265 children with bone and joint infections (106 withosteomyelitis, 25 with osteomyelitis and septic arthritis), the mean WBC count was 12,600/microL atthe time of presentation [45].

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The WBC count tends to be higher and take longer to normalize in children with osteomyelitiscaused by methicillin-resistant S. aureus (MRSA), group A Streptococcus, or Streptococcuspneumoniae and children with concomitant septic arthritis than in other clinical scenarios [46-50].

Erythrocyte sedimentation rate – Elevation of the erythrocyte sedimentation rate (ESR) (≥20mm/h) occurs in most children with osteomyelitis. In a 2012 systematic review, ESR was elevated in91 percent of children at the time of presentation, peaked on day 3 to 5, and normalized over threeto four weeks [2]. In a prospective study of 265 children with bone and joint infections (106 withosteomyelitis, 25 with osteomyelitis and septic arthritis), the mean ESR was 51 mm/h at the time ofpresentation [45].

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The ESR tends to be higher and take longer to normalize in children with MRSA osteomyelitis andchildren with concomitant septic arthritis [46,47,51].

C-reactive protein – Elevation of the C-reactive protein occurs in most children with osteomyelitis.In the 2012 systematic review, CRP was elevated in 81 percent of children at the time ofpresentation, peaked on day 2, and normalized over one week [2]. In a prospective study of 265children with bone and joint infections (106 with osteomyelitis, 25 with osteomyelitis and septicarthritis), the mean CRP was 87 mg/L (8.7 mg/dL) at the time of presentation [45].

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The CRP tends to be higher and take longer to normalize in children with MRSA osteomyelitis andchildren with concomitant septic arthritis [46,47,51-53].

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for specific imaging modalities in children being evaluated for osteomyelitis are discussed separately(table 3). (See "Hematogenous osteomyelitis in children: Evaluation and diagnosis".)

DIAGNOSIS

The evaluation and diagnostic approach to hematogenous osteomyelitis in children are discussed indetail separately. Diagnostic criteria are summarized below. (See "Hematogenous osteomyelitis inchildren: Evaluation and diagnosis".)

The diagnosis is confirmed by histopathologic evidence of inflammation in a surgical specimen of bone(picture 1A-C) (if obtained) or identification of a pathogen by culture or Gram stain in an aspirate orbiopsy of bone [14].

The diagnosis is probable in a child with compatible clinical, laboratory, and/or radiologic findings (table2) in whom a pathogen is isolated from blood, periosteal collection, or joint fluid. We also consider thediagnosis to be probable in a child with compatible clinical, laboratory, and radiologic findings andnegative cultures if he or she responds as expected to empiric antimicrobial therapy.

The diagnosis is unlikely if advanced imaging studies (usually magnetic resonance imaging or

Radiographs – Radiographic findings associated with osteomyelitis include deep soft tissue swelling(image 2), periosteal reaction (suggestive of new bone formation or reactive edema), periostealelevation (suggestive of subperiosteal abscess) (image 3), and lytic sclerosis (suggestive ofsubacute/chronic infection) (image 4).

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Magnetic resonance imaging – Magnetic resonance imaging abnormalities of osteomyelitis areapparent earlier than radiographic abnormalities [55]. Areas of active inflammation show adecreased signal in T1-weighted images and an increased signal in T2-weighted images [56]. Fat-suppression sequences, including short tau inversion recovery, decrease the signal from fat and aremore sensitive for the detection of bone marrow edema. The penumbra sign (high-intensity-signaltransition zone between abscess and sclerotic bone marrow in T1-weighted images (image 5)) ischaracteristic of osteomyelitis [57].

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Scintigraphy – Focal uptake of tracer in the third phase of a three-phase bone scan is associatedwith osteomyelitis.

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Computed tomography – Computed tomography findings of osteomyelitis include increaseddensity of bone marrow, cortex destruction, periosteal reaction (new bone formation), periostealpurulence, and sequestra.

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Ultrasonography – Ultrasonography findings compatible with osteomyelitis include fluid collectionadjacent to the bone without intervening soft tissue, elevation of the periosteum by more than 2 mm,and thickening of the periosteum.

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scintigraphy) are normal.

COMPLICATIONS

Musculoskeletal — Musculoskeletal complications of osteomyelitis vary with age, site of involvement,pathogen, and duration of infection. They include [13,17-19,58-62]:

Venous thrombosis — Venous thrombosis and septic emboli may occur in older children andadolescents with osteomyelitis (image 8) [9,65-68]. Although the pathogenesis is uncertain, smallobservational studies suggest that venous thrombosis and septic emboli in children with osteomyelitis areassociated with [9,65,67-69]:

Extension of infection into the soft tissue (eg, pyomyositis), common in young infants.●

Septic arthritis if infection spreads to the joint space (more common with infections of the proximalhumerus and femur) or with hematogenous delivery of organisms to the joint space (image 6).

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Abnormal bone growth (angular deformity, shortening (image 7A), or overgrowth (image 7B)) withinvolvement of the physis and epiphysis (more common in newborns and community-acquiredmethicillin-resistant S. aureus [CA-MRSA] infections).

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Subperiosteal abscess (image 3).●

Brodie abscess (image 1).●

Pathologic fracture (more common with CA-MRSA) [63].●

Multifocal infection (more common with CA-MRSA or B. henselae and in newborns).●

Osteonecrosis (avascular necrosis) of the femoral head.●

Collapse or complete destruction of one or more vertebral bodies, which may be associated withkyphosis or spinal cord compression.

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Devitalized bone (sequestra) and cutaneous fistulae.●

Chronic osteomyelitis (radiographic evidence of devitalized bone and ≥2 weeks of signs andsymptoms of bone inflammation) occasionally occurs in a child who has longstandingmusculoskeletal complaints that are not recognized as osteomyelitis [64]. However, it is usuallydescribed in patients with inadequate duration of therapy. (See "Hematogenous osteomyelitis inchildren: Management", section on 'Chronic osteomyelitis'.)

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Age ≥8 years●

Occurrence at sites adjacent to the osteomyelitis●

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SUMMARY

S. aureus osteomyelitis, particularly MRSA and Panton-Valentine leukocidin-positive strains

Coagulation abnormalities (eg, heterozygous for factor V Leiden mutation, increasedantiphospholipid antibodies or factor VIII concentrations, positive lupus anticoagulant), some ofwhich were transient

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Disseminated infection●

C-reactive protein >60 mg/L (6 mg/dL) at presentation●

Increased severity of infection (eg, longer hospitalization, more surgical procedures)●

The initial symptoms of osteomyelitis can be nonspecific (eg, malaise, low-grade fever) in children ofall ages. Once the infection becomes established in bone, symptoms are more localized. Childrenwith osteomyelitis usually present with fever, constitutional symptoms (irritability, decreased appetite,decreased activity), focal findings of bone inflammation (warmth, swelling, point tenderness), andlimitation of function (eg, limp, limited use of extremity). (See 'Clinical presentation' above.)

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Clinical features may vary with age:●

In young infants (zero to three months of age), initial clinical features may be mild andnonspecific. Bone infection may spread to the adjacent soft tissues and joints. (See 'Birth tothree months' above.)

•

In older infants and young children, clinical features may include limp; refusal to crawl, walk, sit,or bear weight; irritability when picked up; point tenderness over the infected bone; andcontiguous edema. (See 'Older infants and toddlers' above.)

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In older children and adolescents, clinical features may include complaints of localized pain andfocal examination findings (point tenderness). (See 'Older children and adolescents' above.)

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Children with osteomyelitis of the vertebral bodies usually are older than eight years and complain ofdull, constant back pain. Examination findings may include tenderness with percussion of the spinaldorsal process, spasm of the paraspinous muscles around the involved vertebrae, and pain withflexion or extension of the spine. (See 'Spine' above.)

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REFERENCES

1. Goergens ED, McEvoy A, Watson M, Barrett IR. Acute osteomyelitis and septic arthritis in children.J Paediatr Child Health 2005; 41:59.




5. Asmar BI. Osteomyelitis in the neonate. Infect Dis Clin North Am 1992; 6:117.

6. Fox L, Sprunt K. Neonatal osteomyelitis. Pediatrics 1978; 62:535.

Discitis is more common in children younger than five years and usually occurs in the lumbarregions. Clinical features include gradual onset of irritability and back pain, limp, or refusal to crawl orwalk, without systemic toxicity. Examination findings may include percussion tenderness over theinvolved spine, hip pain and stiffness, loss of lumbar lordosis, neurologic findings (decreased musclestrength or reflexes), and ileus (with lesions of T8 to L1). (See 'Spine' above.)

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Children with pelvic osteomyelitis may complain of hip pain or gait abnormality, but also may localizepain to the thigh, abdomen, lumbar spine, or buttocks. Examination findings may include pointtenderness and pain when the hip is simultaneously flexed, abducted, and externally rotated. (See'Pelvis' above.)

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Laboratory features of osteomyelitis include elevations in erythrocyte sedimentation rate and C-reactive protein. Most patients do not have an elevated peripheral white blood cell count at the timeof presentation. (See 'Laboratory features' above.)

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Radiographic features of osteomyelitis depend upon the imaging modality (table 2). (See'Radiographic features' above.)

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Complications of osteomyelitis include extension of infection into the soft tissues, septic arthritis,abnormal bone growth (image 7A-B), subperiosteal or intraosseous abscess, pathologic fracture,devitalized bone, chronic osteomyelitis, and venous thrombosis. (See 'Complications' above.)

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The evaluation and diagnosis of hematogenous osteomyelitis in children are discussed separately.(See "Hematogenous osteomyelitis in children: Evaluation and diagnosis".)

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7. Bergdahl S, Ekengren K, Eriksson M. Neonatal hematogenous osteomyelitis: risk factors for long-term sequelae. J Pediatr Orthop 1985; 5:564.

8. Gonzalez BE, Martinez-Aguilar G, Hulten KG, et al. Severe Staphylococcal sepsis in adolescents inthe era of community-acquired methicillin-resistant Staphylococcus aureus. Pediatrics 2005;115:642.

9. Gonzalez BE, Teruya J, Mahoney DH Jr, et al. Venous thrombosis associated with staphylococcalosteomyelitis in children. Pediatrics 2006; 117:1673.

10. Foster CE, Taylor M, Schallert EK, et al. Brodie Abscess in Children: A 10-Year Single InstitutionRetrospective Review. Pediatr Infect Dis J 2019; 38:e32.

11. Gafur OA, Copley LA, Hollmig ST, et al. The impact of the current epidemiology of pediatricmusculoskeletal infection on evaluation and treatment guidelines. J Pediatr Orthop 2008; 28:777.

12. Martínez-Aguilar G, Avalos-Mishaan A, Hulten K, et al. Community-acquired, methicillin-resistantand methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children. PediatrInfect Dis J 2004; 23:701.

13. Erdem G, Watson JR, Hunt WG, et al. Clinical and Radiologic Manifestations of Bone Infection inChildren with Cat Scratch Disease. J Pediatr 2018; 201:274.

14. Krogstad P. Osteomyelitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry JD, Harrison G, Kaplan SL, et al (Eds), Elsevier, Philadelphia 2018. p.516.

15. Stone B, Street M, Leigh W, Crawford H. Pediatric Tibial Osteomyelitis. J Pediatr Orthop 2016;36:534.


17. Overturf GD. Bacterial infections of the bones and joints. In: Infectious Diseases of the Fetus and Newborn Infant, 7th, Remington JS, Klein JO (Eds), Elsevier Saunders, Philadelphia 2011. p.296.

18. Ein SH, Shandling B, Humphreys R, Krajbich I. Osteomyelitis of the cervical spine presenting as aneurenteric cyst. J Pediatr Surg 1988; 23:779.

19. Barton LL, Villar RG, Rice SA. Neonatal group B streptococcal vertebral osteomyelitis. Pediatrics1996; 98:459.

20. Karabouta Z, Bisbinas I, Davidson A, Goldsworthy LL. Discitis in toddlers: a case series and review.Acta Paediatr 2005; 94:1516.

21. Chandrasenan J, Klezl Z, Bommireddy R, Calthorpe D. Spondylodiscitis in children: a retrospective






























series. J Bone Joint Surg Br 2011; 93:1122.

22. Spencer SJ, Wilson NI. Childhood discitis in a regional children's hospital. J Pediatr Orthop B 2012;21:264.

23. Garron E, Viehweger E, Launay F, et al. Nontuberculous spondylodiscitis in children. J PediatrOrthop 2002; 22:321.

24. Kumar J, Ramachandran M, Little D, Zenios M. Pelvic osteomyelitis in children. J Pediatr Orthop B2010; 19:38.

25. Weber-Chrysochoou C, Corti N, Goetschel P, et al. Pelvic osteomyelitis: a diagnostic challenge inchildren. J Pediatr Surg 2007; 42:553.

26. Davidson D, Letts M, Khoshhal K. Pelvic osteomyelitis in children: a comparison of decades from1980-1989 with 1990-2001. J Pediatr Orthop 2003; 23:514.

27. Mustafa MM, Sáez-Llorens X, McCracken GH Jr, Nelson JD. Acute hematogenous pelvicosteomyelitis in infants and children. Pediatr Infect Dis J 1990; 9:416.

28. Bocchini CE, Hulten KG, Mason EO Jr, et al. Panton-Valentine leukocidin genes are associatedwith enhanced inflammatory response and local disease in acute hematogenous Staphylococcusaureus osteomyelitis in children. Pediatrics 2006; 117:433.

29. McCaskill ML, Mason EO Jr, Kaplan SL, et al. Increase of the USA300 clone among community-acquired methicillin-susceptible Staphylococcus aureus causing invasive infections. Pediatr InfectDis J 2007; 26:1122.

30. Ritz N, Curtis N. The role of Panton-Valentine leukocidin in Staphylococcus aureus musculoskeletalinfections in children. Pediatr Infect Dis J 2012; 31:514.

31. Ju KL, Zurakowski D, Kocher MS. Differentiating between methicillin-resistant and methicillin-sensitive Staphylococcus aureus osteomyelitis in children: an evidence-based clinical predictionalgorithm. J Bone Joint Surg Am 2011; 93:1693.

32. Gaviria-Agudelo C, Aroh C, Tareen N, et al. Genomic Heterogeneity of Methicillin ResistantStaphylococcus aureus Associated with Variation in Severity of Illness among Children with AcuteHematogenous Osteomyelitis. PLoS One 2015; 10:e0130415.

33. Ceroni D, Cherkaoui A, Ferey S, et al. Kingella kingae osteoarticular infections in young children:clinical features and contribution of a new specific real-time PCR assay to the diagnosis. J PediatrOrthop 2010; 30:301.

34. Chometon S, Benito Y, Chaker M, et al. Specific real-time polymerase chain reaction placesKingella kingae as the most common cause of osteoarticular infections in young children. Pediatr



































Infect Dis J 2007; 26:377.

35. Hajjaji N, Hocqueloux L, Kerdraon R, Bret L. Bone infection in cat-scratch disease: a review of theliterature. J Infect 2007; 54:417.

36. Vermeulen MJ, Rutten GJ, Verhagen I, et al. Transient paresis associated with cat-scratch disease:case report and literature review of vertebral osteomyelitis caused by Bartonella henselae. PediatrInfect Dis J 2006; 25:1177.



39. Ho AK, Shrader MW, Falk MN, Segal LS. Diagnosis and initial management of musculoskeletalcoccidioidomycosis in children. J Pediatr Orthop 2014; 34:571.

40. Akakpo-Numado GK, Gnassingbé K, Abalo A, et al. Locations of osteomyelitis in children withsickle-cell disease at Tokoin teaching hospital (Togo). Pediatr Surg Int 2009; 25:723.

41. Berger E, Saunders N, Wang L, Friedman JN. Sickle cell disease in children: differentiatingosteomyelitis from vaso-occlusive crisis. Arch Pediatr Adolesc Med 2009; 163:251.

42. Sexton DJ. Vascular access infections in patients undergoing dialysis with special emphasis on therole and treatment of Staphylococcus aureus. Infect Dis Clin North Am 2001; 15:731.

43. Yu T, Shroyer M, Dimmitt R, et al. Central venous line associated osteomyelitis in children withintestinal failure. J Pediatr Surg Case Rep 2018; 29:66.



46. Khachatourians AG, Patzakis MJ, Roidis N, Holtom PD. Laboratory monitoring in pediatric acuteosteomyelitis and septic arthritis. Clin Orthop Relat Res 2003; :186.

47. Hawkshead JJ 3rd, Patel NB, Steele RW, Heinrich SD. Comparative severity of pediatricosteomyelitis attributable to methicillin-resistant versus methicillin-sensitive Staphylococcus aureus.J Pediatr Orthop 2009; 29:85.

48. Ibia EO, Imoisili M, Pikis A. Group A beta-hemolytic streptococcal osteomyelitis in children.Pediatrics 2003; 112:e22.


































49. Bradley JS, Kaplan SL, Tan TQ, et al. Pediatric pneumococcal bone and joint infections. ThePediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG). Pediatrics 1998;102:1376.

50. Vinod MB, Matussek J, Curtis N, et al. Duration of antibiotics in children with osteomyelitis andseptic arthritis. J Paediatr Child Health 2002; 38:363.

51. Saavedra-Lozano J, Mejías A, Ahmad N, et al. Changing trends in acute osteomyelitis in children:impact of methicillin-resistant Staphylococcus aureus infections. J Pediatr Orthop 2008; 28:569.

52. Unkila-Kallio L, Kallio MJ, Peltola H. The usefulness of C-reactive protein levels in the identificationof concurrent septic arthritis in children who have acute hematogenous osteomyelitis. A comparisonwith the usefulness of the erythrocyte sedimentation rate and the white blood-cell count. J BoneJoint Surg Am 1994; 76:848.

53. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitisand septic arthritis: emergence of community-associated methicillin-resistant Staphylococcusaureus. J Pediatr Orthop 2006; 26:703.

54. Schmit P, Glorion C. Osteomyelitis in infants and children. Eur Radiol 2004; 14 Suppl 4:L44.

55. Saigal G, Azouz EM, Abdenour G. Imaging of osteomyelitis with special reference to children.Semin Musculoskelet Radiol 2004; 8:255.

56. Guillerman RP. Osteomyelitis and beyond. Pediatr Radiol 2013; 43 Suppl 1:S193.

57. Shih HN, Shih LY, Wong YC. Diagnosis and treatment of subacute osteomyelitis. J Trauma 2005;58:83.

58. Peters W, Irving J, Letts M. Long-term effects of neonatal bone and joint infection on adjacentgrowth plates. J Pediatr Orthop 1992; 12:806.

59. Williamson JB, Galasko CS, Robinson MJ. Outcome after acute osteomyelitis in preterm infants.Arch Dis Child 1990; 65:1060.

60. Overturf GD. Bacterial infections of the bone and joints. In: Infectious Diseases of the Fetus and Newborn, 7th ed, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.296.

61. Martínez-Aguilar G, Hammerman WA, Mason EO Jr, Kaplan SL. Clindamycin treatment of invasiveinfections caused by community-acquired, methicillin-resistant and methicillin-susceptibleStaphylococcus aureus in children. Pediatr Infect Dis J 2003; 22:593.

62. McNeil JC, Forbes AR, Vallejo JG, et al. Role of Operative or Interventional Radiology-Guided































Cultures for Osteomyelitis. Pediatrics 2016; 137.

63. Belthur MV, Birchansky SB, Verdugo AA, et al. Pathologic fractures in children with acuteStaphylococcus aureus osteomyelitis. J Bone Joint Surg Am 2012; 94:34.


65. Gorenstein A, Gross E, Houri S, et al. The pivotal role of deep vein thrombophlebitis in thedevelopment of acute disseminated staphylococcal disease in children. Pediatrics 2000; 106:E87.

66. Walsh S, Phillips F. Deep vein thrombosis associated with pediatric musculoskeletal sepsis. JPediatr Orthop 2002; 22:329.

67. Crary SE, Buchanan GR, Drake CE, Journeycake JM. Venous thrombosis and thromboembolism inchildren with osteomyelitis. J Pediatr 2006; 149:537.

68. Hollmig ST, Copley LA, Browne RH, et al. Deep venous thrombosis associated with osteomyelitis inchildren. J Bone Joint Surg Am 2007; 89:1517.

69. Ligon JA, Journeycake JM, Josephs SC, et al. Differentiation of Deep Venous Thrombosis AmongChildren With or Without Osteomyelitis. J Pediatr Orthop 2018; 38:e597.


















GRAPHICS







Sites of involvement in acute hematogenous osteomyelitisin children

Tubular bones are affected more frequently than nontubular (flat) bones orspine.

* This does not include the osteomyelitis of the calcaneum, which accounts for 5%of cases.

Data from: Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute andsubacute paediatric osteomyelitis: a systematic review of the literature. J Bone JointSurg Br 2012; 94:584.




FABERE test (Patrick test, "figure of four" test)

The FABERE test (Patrick test or "figure of four" test) consists of Flexion ofthe hip and knee, with ABduction and External Rotation at the hip, so thatthe ankle of one leg is on top of the opposite knee (a figure fourconfiguration). Force is applied downwards on the bent knee and theopposite hip, causing Extension at the sacroiliac joint ipsilateral to the bentleg. Pain in the sacral region from pelvic torque during the FABERE test, inthe absence of pain with passive motion of the hip joint, suggests discomfortarising from the sacroiliac joint.





Clinical features


























Imagingmodality

Abnormal findings











Computedtomography


Cortex destruction













¶



Comparison of imaging modalities in children with osteomyelitis

Modality Indications Advantages Disadvantages Comments*

Plain radiographs Baseline

Excluding otherconditions indifferential diagnosis

Monitoring diseaseprogression

Inexpensive

Easy to obtain

Abnormal findingsusually not present atonset of symptoms,except in newborns

Sensitivity 16 to 20percent

Specificity 80 to 100percent

Normal radiograph atonset does notexclude osteomyelitis

MRI Identify location andextent of disease

Evaluation of adjacentstructures forextension of infection(soft tissues, growthplate, epiphysis, joint)

Evaluation of difficultsites (eg, pelvis,vertebral bodies,intervertebral discs)

Planning surgicalintervention

No radiation risk

Demonstrates earlychanges in themarrow cavity

Improveddemonstration ofsubperiosteal abscess

Demonstration ofconcomitant septicarthritis, venousthrombosis, orpyomyositis

Costly

Less useful inmultifocal or poorlylocalized disease

Requires more timethan CT

Young children mayrequire sedation oranesthesia

Not always available



Osteomyelitis unlikelyif MRI is normal

Scintigraphy Poorly localizedsymptoms (eg, youngchildren who cannotverbalize)

Multifocal disease

More useful than MRIin multifocal or poorlylocalized disease

Demonstrates earlychanges

Readily available

May require lesssedation than MRI

Radiation exposure

Does not provideinformation aboutextent of purulentcollections that mayrequire drainage



Osteomyelitis unlikelyif scintigraphy isnormal

May be falselynegative if bloodsupply to periosteumis interrupted (eg,subperiosteal abscess)

CT Evaluation of corticaldestruction, bone gas,and sequestrum

Delineating extent ofbone injury insubacute/chronicosteomyelitis

Planning surgicalinterventions

Evaluation ofcomplications if MRInot available orcontraindicated

Less time-consumingthan MRI

Does not requiresedation

Expensive

Increased radiationexposure

Poor soft tissuecontrast



Generally used only ifother studies are notpossible orinconclusive

Ultrasonography Evaluate fluidcollections in adjacentstructures (eg, joint,periosteum)

Monitor abscessresolution orprogression

Inexpensive

No radiation burden

Noninvasive

Portable

Does not penetratebone cortex



MRI: magnetic resonance imaging; CT: computed tomography.* Values for sensitivity and specificity are from: Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and

¶



subacute paediatric osteomyelitis: A systematic review of the literature. J Bone Joint Surg Br 2012; 94:584.¶ Preferred imaging study when imaging other than plain radiographs are necessary to establish the diagnosis of osteomyelitis.

References:1. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatric osteomyelitis: A systematic

review of the literature. J Bone Joint Surg Br 2012; 94:584.2. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch Dis Child 2012; 97:545.3. Peltola H, Pääkkönen M. Acute osteomyelitis in children. N Engl J Med 2014; 370:352.4. Yeo A, Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ 2014; 348:g66.




Early osteomyelitis in a six-year-old with fever and anklepain

Radiographs of the ankle (A) demonstrate deep soft tissue swelling (arrow)inferior to the medial malleolus. A technetium 99m bone scan showsincreased uptake in the distal tibia in the blood flow (B) and bone uptake (C;four hour) phases.





Osteomyelitis with subperiosteal abscess

Radiograph of the femur demonstrates periosteal elevation due to asubperiosteal abscess as the result of osteomyelitis.





Lytic lucency in osteomyelitis

(A) Radiograph at the initial evaluation of a nine-year-old with fever and limpdemonstrates a lytic lucency in the distal femoral metaphysis.(B, C) Axial and coronal magnetic resonance (MR) images delineate the area ofosteomyelitis and adjacent marrow edema.

Reproduced with permission from Jeanne Chow, MD. Children's Hospital-Boston, Copyright ©Jeanne Chow, MD.




Acute osteomyelitis






Magnetic resonance image of left hip effusion

(A) Axial and (B) coronal image of left hip effusion. The bright collection seen around thefemoral neck (arrows) is a left hip effusion. The images were obtained using a fast spinecho-inversion recovery (FSE-IR) sequence, which is fluid sensitive.

Courtesy of Michael Rosenthal, MD, PhD.




Right femoral osteomyelitis complicated by femoralshortening

Standing teleogram 18 months after right femoral osteomyelitis involvingmost of the right femur, which was complicated by femoral shortening.

Courtesy of William A Phillips, MD.




Left femoral osteomyelitis complicated by femoralovergrowth

Standing teleogram 2 years, 3 months after left femoral osteomyelitis, whichwas complicated by left femoral overgrowth resulting in marked pelvic tilt(solid line).

Courtesy of William A Phillips, MD.




Pulmonary septic emboli in community-associatedmethicillin-resistant Staphylococcus aureus (CA-MRSA)osteomyelitis

Computed tomography of the chest in a nine-year-old with CA-MRSAosteomyelitis of the tibia demonstrating multiple nodules consistent withpulmonary emboli.

Courtesy of Sheldon L Kaplan, MD. Texas Children's Hospital.







Osteomyelitis in adults: Clinical manifestations and diagnosis - UpToDate



Osteomyelitis in adults: Clinical manifestations and diagnosisAuthors: Tahaniyat Lalani, MBBS, MHS, Steven K Schmitt, MD, FIDSA Section Editor: Denis Spelman, MBBS, FRACP,FRCPA, MPH Deputy Editor: Elinor L Baron, MD, DTMH


Literature review current through: Feb 2020. | This topic last updated: Mar 28, 2019.

INTRODUCTION

Osteomyelitis is an infection involving bone. Osteomyelitis may be classified based on the mechanism ofinfection (hematogenous versus nonhematogenous) and the duration of illness (acute versus chronic) [1].

Issues related to the classification, epidemiology, microbiology, clinical manifestations, and diagnosis ofosteomyelitis in adults are presented here. Issues related to treatment of osteomyelitis are discussedseparately. (See "Osteomyelitis in adults: Treatment".)

Issues related to vertebral osteomyelitis, pelvic and sacral osteomyelitis, and osteomyelitis in the settingof trauma are discussed in detail separately. (See "Vertebral osteomyelitis and discitis in adults" and"Pelvic osteomyelitis and other infections of the bony pelvis in adults" and "Osteomyelitis associated withopen fractures in adults".)

Issues related to prosthetic joint infections are discussed separately. (See "Prosthetic joint infection:Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Issues related to osteomyelitis in children are discussed separately. (See "Hematogenous osteomyelitisin children: Evaluation and diagnosis" and "Hematogenous osteomyelitis in children: Management".)

CLASSIFICATION

Osteomyelitis may be classified based on the duration of illness (acute versus chronic) and themechanism of infection (hematogenous versus nonhematogenous). This approach to classification wasdescribed by Lew and Waldvogel [2-4].

Acute osteomyelitis typically presents with a symptom duration of a few days or weeks. Sequestra(pieces of necrotic bone that separate from viable bone) are absent.

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Chronic osteomyelitis is characterized by long-standing infection over months or years. Sequestra areusually present; they form as a result of bone ischemia and necrosis in the context of blood vesselcompression due to elevated medullary pressure associated with bone marrow inflammation. Sequestracan be seen radiographically. The presence of a sinus tract is pathognomonic of chronic osteomyelitis.(See "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)

Nonhematogenous osteomyelitis can occur as a result of contiguous spread of infection to bone fromadjacent soft tissues and joints or via direct inoculation of infection into the bone (as a result of trauma orsurgery).

Hematogenous osteomyelitis is caused by microorganisms that seed the bone in the setting ofbacteremia.

NONHEMATOGENOUS OSTEOMYELITIS

Nonhematogenous osteomyelitis can occur as a result of contiguous spread of infection to bone fromadjacent soft tissues and joints or via direct inoculation of infection into the bone (as a result of trauma,bite wounds, or surgery).

Epidemiology — Among younger adults, nonhematogenous osteomyelitis occurs most commonly in thesetting of trauma and related surgery. Among older adults, nonhematogenous osteomyelitis occurs mostcommonly as a result of contiguous spread of infection to bone from adjacent soft tissues and joints(such as in the setting of diabetic foot wounds or decubitus ulcers) [2].

Risk factors for nonhematogenous osteomyelitis include poorly healing soft tissue wounds (includingdecubitus ulcers), presence of orthopedic hardware, diabetes, peripheral vascular disease, andperipheral neuropathy.

Microbiology — Nonhematogenous osteomyelitis may be polymicrobial or monomicrobial.Staphylococcus aureus (including methicillin-resistant S. aureus), coagulase-negative staphylococci, andaerobic gram-negative bacilli are the most common organisms. In one study, staphylococci were isolatedin 53 percent of bone biopsy specimens, enterococci in 8 percent, streptococci in 12 percent, andanaerobes in 5 percent [5].

Other pathogens including corynebacteria, fungi, and mycobacteria have also been implicated [4-8].

Clinical manifestations

Signs and symptoms — Acute osteomyelitis typically presents with gradual onset of symptoms overseveral days. Patients usually present with dull pain at the involved site, with or without movement. Localfindings (tenderness, warmth, erythema, and swelling) and systemic symptoms (fever, rigors) may alsobe present. Patients with osteomyelitis involving the hip, vertebrae, or pelvis tend to manifest few signs orsymptoms other than pain.







Chronic osteomyelitis may manifest as pain, erythema, or swelling, sometimes in association with adraining sinus tract; fever is usually absent. Chronic osteomyelitis may also present with intermittentflares of pain and swelling. The presence of a sinus tract is pathognomonic of chronic osteomyelitis.

The diagnosis of chronic osteomyelitis can be particularly challenging when prosthetic material, extensiveskin or soft tissue ulceration, or ischemic changes due to vascular insufficiency are also present [9]. Deepor extensive ulcers that fail to heal after several weeks of appropriate ulcer care should raise suspicionfor chronic osteomyelitis, particularly when such lesions overlie bony prominences [9,10]. Chronicosteomyelitis may also present as a nonhealing fractures.

Patients with diabetes and chronic osteomyelitis may present with atypical findings. Diabetics whodevelop cutaneous ulcers often develop osteomyelitis before exposed bone is present on exam [9]. If adiabetic foot ulcer is larger than 2 cm or if exposed bone is present, osteomyelitis is highly likely [9,11].(See "Clinical manifestations, diagnosis, and management of diabetic infections of the lowerextremities".)

Osteomyelitis of the foot may develop following nail puncture through a shoe; Pseudomonas aeruginosais a typical pathogen in such cases. (See "Infectious complications of puncture wounds" and"Pseudomonas aeruginosa skin and soft tissue infections", section on 'Infection following nail puncture'.)

Probing to bone — Probing to bone with a sterile blunt metal tool should be included in the initialassessment of diabetic patients with infected pedal ulcers. A positive result consists of detection of ahard, gritty surface [10-12]. The reliability of the probe-to-bone test may vary by the ulcer location and theexpertise of the clinician performing the test [13,14].

The performance characteristics of the test have been evaluated in the setting of diabetic foot ulcers. Inpractice, the test is also used for evaluating nondiabetic ulcers due to peripheral neuropathy,vasculopathy, or pressure sores, although the performance characteristics have not been evaluated inthese settings.

In a systematic review evaluating the performance of the probe-to-bone test (using bone histopathologyor culture as the reference standard), the pooled sensitivity and specificity for the test were 87 and 83percent, respectively [15]. An important limitation was the potential for selection and verification bias; thestudies included in the analysis did not specify whether the results of the probe-to-bone test influencedpursuit of bone biopsy or culture nor whether interpreters of the reference standard were blinded toresults of the probe-to-bone test.

The probe-to-bone test should be used as a screening tool in conjunction with the patient's pretestprobability for osteomyelitis to determine whether additional tests (such as radiographic imaging or bonebiopsy) are needed for diagnosis of diabetic foot osteomyelitis [16].

Laboratory tests — Laboratory findings are nonspecific. In the setting of acute osteomyelitis,leukocytosis and elevated serum inflammatory markers (erythrocyte sedimentation rate [ESR] and/or C-

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reactive protein [CRP]) may be observed [17]. In the setting of chronic osteomyelitis, leukocytosis isuncommon; the ESR and/or CRP may be elevated or normal [18,19].

HEMATOGENOUS OSTEOMYELITIS

Hematogenous osteomyelitis is caused by microorganisms that seed the bone in the setting ofbacteremia.

Epidemiology — Hematogenous osteomyelitis occurs most commonly in children [20]. (See"Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology".)

Vertebral osteomyelitis is the most common form of hematogenous osteomyelitis in adults. Issues relatedto vertebral osteomyelitis are discussed separately. (See "Vertebral osteomyelitis and discitis in adults".)

Among adults, hematogenous osteomyelitis accounts more frequently in males. Most cases occur inpatients >50 years [21], except for injection drug users, most of whom are <40 years of age [22].

Risk factors for hematogenous osteomyelitis include endocarditis, presence of indwelling intravasculardevices (eg, vascular catheters, cardiovascular devices) or orthopedic hardware, injection drug use,hemodialysis, and sickle cell disease [23].

Microbiology — Hematogenous osteomyelitis occurs following bacteremia. Patients may presentfollowing clearance of bacteremia, so blood cultures are not always positive.

Hematogenous osteomyelitis is usually monomicrobial; S. aureus is by far the most commonly isolatedorganism. In some cases, hematogenous osteomyelitis due to S. aureus presents with multifocalinvolvement [2,24-26]. Aerobic gram-negative rods are identified in up to 30 percent of cases.

Among injection drug users, hematogenous osteomyelitis due to P. aeruginosa and Serratia marcescenshas been described [27]. Among immunosuppressed patients, hematogenous osteomyelitis due toAspergillus spp has been described [28].

Hematogenous osteomyelitis due to beta-hemolytic streptococci is relatively rare (<1 percent of cases)[29]. Other less common pathogens include Mycobacterium tuberculosis [30], Candida spp [31-33],Bartonella henselae [34], Coccidioides immitis [35,36], and Cutibacterium (formerly Propionibacterium)acnes [37].

Clinical manifestations

Signs and symptoms — In general, signs and symptoms of hematogenous osteomyelitis may beindistinguishable from those of nonhematogenous osteomyelitis, discussed above. (See 'Signs andsymptoms' above.)

Signs and symptoms referable to specific forms of hematogenous osteomyelitis are discussed in thefollowing sections.









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Forms of disease — Clinical manifestations of hematogenous osteomyelitis mirror those ofnonhematogenous osteomyelitis. (See 'Clinical manifestations' above.)

Clinical presentations that are unique to hematogenous osteomyelitis are discussed in the followingsections. In some cases, adults with hematogenous osteomyelitis may have no local symptoms referableto bones; soft tissue findings may be more prominent.

Vertebral osteomyelitis – Vertebral osteomyelitis is the most common form of hematogenousosteomyelitis in adults. Issues related to vertebral osteomyelitis are discussed separately. (See"Vertebral osteomyelitis and discitis in adults".)

●

Sternoclavicular and pelvic osteomyelitis – After vertebral osteomyelitis, next most common sitesof hematogenous osteomyelitis in adults are the flat bones of the axial skeleton (such as thesternoclavicular and pelvic bones). These sites are involved most frequently among injection drugusers; multifocal involvement may be observed in these patients [38-40].

●

Specific signs and symptoms of sternoclavicular osteomyelitis include anterior chest wall swelling,pain, and tenderness. Sternoclavicular osteomyelitis may present as a mass that is mistaken for asoft tissue abscess or atypical cellulitis. It can also present as infection of the manubriosternalsymphysis (a fibrocartilage union of the manubrium and the body of the sternum). In addition,sternoclavicular osteomyelitis can develop as a complication of mediastinitis. Local symptomsinclude pain, swelling, erythema, and tenderness over the sternoclavicular joint, and infection canextend into the surrounding soft tissue including the pectoralis major. (See "Postoperativemediastinitis after cardiac surgery".)

Issues related to pelvic osteomyelitis are described separately. (See "Pelvic osteomyelitis and otherinfections of the bony pelvis in adults".)

Long-bone osteomyelitis – The least common sites of hematogenous osteomyelitis in adults arethe long bones of the appendicular skeleton (in contrast, this is the most common site ofhematogenous osteomyelitis in children) [41]. The clinical presentation is variable; some presentsubacutely with low-grade fever and vague pain at the site of infection, while others present acutelywith high fever, sharp pain, and swelling over the involved site. Long-bone osteomyelitis may beclassified based on the degree of bone involvement as well as host factors (table 1) [42]. (See"Hematogenous osteomyelitis in children: Clinical features and complications".)

●

Long-bone osteomyelitis can also present as septic arthritis of the knee, hip, or shoulder. This occursif infection within the metaphysis (the most common site of infection in long-bone osteomyelitis)breaks through the bone cortex, leading to discharge of pus into the joint. The clinical manifestations,diagnosis, and management of septic arthritis are described separately. (See "Septic arthritis inadults".)

Brodie abscess – A Brodie abscess consists of a region of suppuration and necrosis•



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COMPLICATIONS

Complications of osteomyelitis include:

encapsulated by granulation tissue within a rim of sclerotic bone. Brodie abscess occurs in thesetting of subacute or chronic osteomyelitis in the metaphysis of long bones, typically in patients<25 years of age [43]. It is usually of hematogenous origin but can also occur in the setting oftrauma.

The most common pathogen is S. aureus; other gram-positive and gram-negative organisms(including P. aeruginosa, Klebsiella spp, and other gram-negative rods) may be seen. Culturesmay be sterile in up to half of cases.

Patients with Brodie abscess typically present with insidious onset of mild to moderate painlasting for several weeks to months, with or without fever. If the subacute process progresses tochronic localized bone abscess, patients present with longstanding dull pain in the absence offever [44,45]. The most common site is the distal tibia; other sites include the femur, fibula,radius, and ulna [46].

Radiography typically demonstrates a single lesion near the metaphysis (image 1).

Osteomyelitis in sickle cell disease – Osteomyelitis is a common complication of sickle celldisease; it occurs in more than 10 percent of patients [1]. This issue is discussed furtherseparately. (See "Acute and chronic bone complications of sickle cell disease", section on'Osteomyelitis and septic arthritis'.)

•

Emphysematous osteomyelitis - Emphysematous osteomyelitis is a rare form of osteomyelitischaracterized by intraosseous gas in the extra-axial skeleton (eg, pelvis, sacrum, lower extremitybones) or vertebrae [47-49]. It can occur via hematogenous spread or via contiguous spread from anintra-abdominal source, is usually associated with underlying comorbidities (eg, diabetes ormalignancy), and may be monomicrobial or polymicrobial. The most commonly associatedorganisms include Enterobacteriaceae and Fusobacterium necrophorum.

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Sinus tract formation●

Contiguous soft tissue infection●

Abscess●

Septic arthritis●

Systemic infection●

Bony deformity●

Fracture [50]●

Malignancy [51-58]●




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DIAGNOSIS

Overview — A clinical presentation of osteomyelitis should be suspected in the following circumstances:

In general, the diagnosis of osteomyelitis is established via culture obtained from biopsy of the involvedbone [10].

A diagnosis of osteomyelitis may be inferred in the following circumstances:

Issues related to diagnosis of vertebral osteomyelitis are discussed separately. (See "Vertebralosteomyelitis and discitis in adults".)

Clinical approach — Initial evaluation of patients with suspected osteomyelitis includes history andphysical examination; predisposing factors or events should be elicited (such as underlying diabetes,vasculopathy, invasive procedures, or injection drug use). (See 'Epidemiology' above and 'Epidemiology'above.)

If osteomyelitis is suspected based on clinical history and physical findings, laboratory evaluation(including erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], white blood cell count), bloodcultures, and radiographic imaging should be obtained. ESR and CRP are sensitive but not specific forosteomyelitis; if elevated initially, they can be useful for treatment monitoring. (See "Osteomyelitis inadults: Treatment", section on 'Laboratory monitoring'.)

In patients with ≥2 weeks of symptoms, conventional radiography is a reasonable initial imaging modalityfor evaluation of suspected osteomyelitis. In patients with <2 weeks of symptoms, an advanced imagingmodality should be pursued. Advanced imaging is also warranted for patients with diabetes, localized

Nonhematogenous osteomyelitis should be suspected in the setting of new or worseningmusculoskeletal pain, particularly in patients with poorly healing soft tissue or surgical woundsadjacent to bony structures, in patients with signs of cellulitis overlying previously implantedorthopedic hardware, and in patients with traumatic injury (including bite and puncture wounds). Itshould also be suspected in diabetic patients with ulcers that probe to bone.

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Hematogenous osteomyelitis should be suspected in the setting of new or worseningmusculoskeletal pain, particularly in the setting of fever and/or recent bacteremia.

●

Clinical and radiographic findings typical of osteomyelitis and positive blood cultures with a likelypathogen (such as S. aureus); in such cases, bone biopsy is not required but may be useful,particularly if subsequent therapeutic debridement is needed.

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Bone histopathology consistent with osteomyelitis in the absence of positive culture data (particularlyin the setting of recent antibiotic administration).

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Suggestive clinical and typical radiographic findings and persistently elevated inflammatory markersin circumstances with no positive culture data and a biopsy is not feasible.

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symptoms, and/or abnormal laboratory results whose plain radiographs are normal or suggestive ofosteomyelitis without characteristic features.

The optimal radiographic modality may depend upon specific clinical circumstances and should betailored accordingly for individual patients, in discussion with radiologist expertise if necessary. Thefollowing concepts may help guide selection of radiographic modality (see "Approach to imagingmodalities in the setting of suspected nonvertebral osteomyelitis"):

Findings of osteomyelitis on radiographic imaging should prompt bone biopsy for culture and histology toconfirm the diagnosis and to guide antimicrobial therapy, unless blood cultures are positive for a likelypathogen (such as S. aureus, a gram-negative enteric rod, or P. aeruginosa). Osteomyelitis is unlikely inthe absence of radiographic evidence on MRI, CT, or nuclear imaging.

If blood cultures and needle aspirate cultures are negative and the clinical suspicion for osteomyelitisremains high on the basis of clinical and radiographic findings, repeat bone biopsy (either percutaneousor open) should be performed. If this specimen is also nondiagnostic, an empiric antimicrobial regimenshould be initiated against common gram-positive and gram-negative bacterial pathogens. (See"Osteomyelitis in adults: Treatment".)

If there is evidence of soft tissue infection over a bony surface without radiographic evidence ofosteomyelitis, an empiric course of therapy for soft tissue infection may be appropriate [10].

Blood cultures — Blood cultures are positive in about half of cases of acute osteomyelitis; their utility ishighest in the setting of hematogenous infection [2,59,60]. The yield of blood cultures is likely greatest inthe setting of associated fever and/or in the setting of suspected vertebral osteomyelitis or suspectedconcurrent infective endocarditis.

Positive blood cultures may obviate the need for invasive diagnostic testing if the organism isolated fromblood is a pathogen likely to cause osteomyelitis.

Bone biopsy — Bone biopsy (open or percutaneous) should be obtained for pathogen identification andto obtain susceptibility data when this is feasible; biopsy is also useful if the diagnosis of osteomyelitis isuncertain [5,24,61-63]. Cultures of bone biopsy material yield positive findings in up to 87 percent ofcases [62]. Cultures of swabs or material from needle puncture (eg, aspiration of material in the softtissue rather than bone) should not be used to establish an osteomyelitis pathogen, since the correlationbetween bone biopsy culture and these specimens is poor, especially in cases of diabetic foot infectionsor decubitus ulcers [5,64].

If the patient is diabetic and has symptoms referable to the foot, magnetic resonance imaging (MRI)is the test of choice.

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If metal hardware precludes MRI or computed tomography (CT), a nuclear study is the test of choice.The limitations of nuclear studies are discussed separately and should be considered ininterpretation of results.

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Cessation of antibiotics 48 to 72 hours prior to bone biopsy may increase the microbiological yield, butoften bone cultures are positive regardless of prior antibiotic therapy because such infections occur inareas of simultaneous infection-induced bony infarction or ischemia.

Open biopsy is preferable over needle biopsy. In circumstances where surgical debridement is required(such as decubitus ulcers or wounds with compromised vasculature), bone samples should be obtainedat the time of surgical debridement [65].

Percutaneous needle biopsy is an alternative to open biopsy; this technique is less reliable than openbiopsy given problems with sampling error. This was illustrated in a study including 31 diabetic patients inwhich culture results from needle biopsies were compared with open biopsies; needle biopsy had a loweryield than open biopsy, and the correlation between culture results obtained by needle biopsy and openbiopsy was only 23 percent [64]. In addition, the sensitivity of needle biopsy can be particularly low inpostoperative or post-traumatic settings [62,66]. If the clinical suspicion for osteomyelitis is high in thesetting of negative cultures from blood and needle biopsy, the needle biopsy should be repeated or anopen biopsy performed.

Percutaneous procedures should be performed through intact tissues (rather than inflamed or ulceratedskin) to obtain accurate culture results. Fluoroscopic or CT guidance for percutaneous procedures ispreferable. Ideally, the biopsy should be obtained prior to treatment with antimicrobial therapy. At leasttwo specimens should be obtained so that one can be sent for Gram stain and culture (including aerobicanaerobic, mycobacterial, and fungal studies) and the other for histopathology.

Bone biopsy may not be needed for patients with radiographic studies consistent with osteomyelitis in thesetting of positive blood cultures or when prior bone cultures have been obtained in a patient with clearevidence for relapse of prior bone infection. In addition, it may be impractical to obtain a bone biopsy insome circumstances since the biopsy site may heal poorly in the setting of advanced vascular disease. Insuch cases, empiric management should be pursued. (See "Osteomyelitis in adults: Treatment".)

Cultures — The identification of the causative pathogen(s) is crucial and is best accomplished bybone biopsy (obtained surgically or by radiographically guided intervention). At least two specimensshould be obtained so that one can be sent for Gram stain and culture (including aerobic, anaerobic,mycobacterial, and fungal cultures) and the other can be sent for histopathology [67].

Sinus tract cultures may be of some use for prediction of osteomyelitis if S. aureus or Salmonella spp areidentified; however, in general, such cultures are not worthwhile because the results do not correlatereliably with the pathogen in the underlying bone [5,66,68-70]. In one report of 40 patients with chronicosteomyelitis, only 44 percent of sinus tract cultures contained the pathogen isolated from a deepsurgical specimen [70]. Isolation of S. aureus from the sinus tract culture had some predictive value,although the absence of S. aureus in the sinus tract did not preclude its presence on bone biopsy.Culturing other organisms is not predictive for those that will be found on bone biopsy [70].

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fixation hardware, although this procedure is not routinely available in most microbiology laboratories[17,71,72].

Histopathology — Histopathologic features of osteomyelitis include necrotic bone with extensiveresorption adjacent to an inflammatory exudate [73]. Stains for bacteria, mycobacteria, and fungi shouldbe on histopathology specimens. Histopathology is discussed further separately. (See "Pathogenesis ofosteomyelitis".)

Radiography — The general role of radiographic studies in the diagnosis of osteomyelitis is discussedabove. (See 'Clinical approach' above.)

A more detailed discussion of radiographic modalities in the setting of suspected osteomyelitis isdiscussed separately. (See "Approach to imaging modalities in the setting of suspected nonvertebralosteomyelitis".)


The differential diagnosis of osteomyelitis includes:

Soft tissue infection – Soft tissue infection may occur alone or in conjunction with osteomyelitis. Ingeneral, it is prudent to pursue imaging for assessment of bone involvement in the setting of chronicsoft tissue infection that fails to improve with appropriate antibiotic therapy; this occurs more often inthe setting of diabetes. (See "Clinical manifestations, diagnosis, and management of diabeticinfections of the lower extremities".)

●

Charcot arthropathy – Acute Charcot neuroarthropathy may present with localized erythema andwarmth; it can be difficult to determine if such patients have Charcot arthropathy or osteomyelitis (orboth). Furthermore, patients with Charcot arthropathy commonly develop skin ulcerations that can inturn lead to secondary osteomyelitis. Magnetic resonance imaging (MRI; contrast-enhanced) may bediagnostically useful if it shows a sinus tract, replacement of soft tissue fat, a fluid collection, orextensive marrow abnormalities. Bone biopsy may be needed for definitive diagnosis. (See "Diabeticneuropathic arthropathy".)

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Osteonecrosis – Osteonecrosis (avascular necrosis of bone) is usually relatively easy to distinguishfrom osteomyelitis since a precipitating cause is usually present (such as steroids, radiation, orbisphosphonate use). Associated osteomyelitis may occur in patients with mandibular osteonecrosis.(See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy",section on 'Osteonecrosis of the jaw' and "Osteonecrosis (avascular necrosis of bone)".)

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Gout – Both osteomyelitis and gout can present with joint inflammation; the presentation of gout isusually more acute than the presentation of osteomyelitis. Gout is distinguished by presence of uricacid crystals in joint fluid. (See "Clinical manifestations and diagnosis of gout".)

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Fracture – Osteomyelitis may mimic the appearance of fracture on radiographic imaging; fracture istypically associated with antecedent trauma. In some cases, bone biopsy may be required todistinguish these two entities, particularly in the absence of healing following suspected fracture.(See "General principles of fracture management: Early and late complications".)

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Bursitis – Both osteomyelitis and bursitis can present with inflammation of the bursa; osteomyelitisinvolves infection of the underlying bone whereas bursitis involves infection that is confined to thebursa. The two are distinguished by clinical history, physical examination, radiography, and bursaaspiration. (See "Septic bursitis".)

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Bone tumor – Both osteomyelitis and bone tumor may present with bone pain [74,75]; bone tumor isgenerally distinguished by radiographic imaging and bone biopsy. (See "Bone tumors: Diagnosis andbiopsy techniques".)

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Sickle cell vaso-occlusive pain crisis – In patients with sickle cell disease, the clinical presentation ofosteomyelitis may be difficult to distinguish from a vaso-occlusive pain crisis. Osteomyelitis is morelikely to be associated with a prolonged duration of fever and pain localized to a single site. (See"Acute and chronic bone complications of sickle cell disease", section on 'Osteomyelitis and septicarthritis'.)

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Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) – SAPHO syndrome consists of awide spectrum of neutrophilic dermatoses associated with aseptic osteoarticular lesions. It can mimicosteomyelitis in patients who lack the characteristic findings of pustulosis and synovitis. Thediagnosis is established via clinical manifestations; bone culture is sterile in the setting of osteitis.(See "SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome" and "Major causes ofmusculoskeletal chest pain in adults", section on 'Sternocostoclavicular hyperostosis (SAPHOsyndrome)'.)

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Complex regional pain syndrome (CRPS) – CRPS is characterized by pain, swelling, limited range ofmotion, skin changes, and patchy bone demineralization, usually of the distal limbs. It frequentlybegins following a fracture, soft tissue injury, or surgery. Patients with osteomyelitis lack symptomsof vasomotor instability observed with CRPS. Radiographic evaluation with MRI can differentiatebetween osteomyelitis and CRPS. (See "Complex regional pain syndrome in adults: Pathogenesis,clinical manifestations, and diagnosis".)

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INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." TheBasics patient education pieces are written in plain language, at the 5 to 6 grade reading level, andthey answer the four or five key questions a patient might have about a given condition. These articlesare best for patients who want a general overview and who prefer short, easy-to-read materials. Beyondthe Basics patient education pieces are longer, more sophisticated, and more detailed. These articles arewritten at the 10 to 12 grade reading level and are best for patients who want in-depth information andare comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or emailthese topics to your patients. (You can also locate patient education articles on a variety of subjects bysearching on "patient info" and the keyword(s) of interest.)

SUMMARY

th th

th th

Basics topic (see "Patient education: Osteomyelitis in adults (The Basics)")●

Osteomyelitis is an infection involving bone. Osteomyelitis may be classified based on themechanism of infection (hematogenous versus nonhematogenous) and the duration of illness (acuteversus chronic). Nonhematogenous osteomyelitis can occur as a result of contiguous spread ofinfection to bone from adjacent soft tissues and joints or via direct inoculation of infection into thebone (as a result of trauma, bite wounds, or surgery). Hematogenous osteomyelitis is caused bymicroorganisms that seed the bone in the setting of bacteremia. (See 'Classification' above.)

●

Nonhematogenous osteomyelitis should be suspected in the setting of new or worseningmusculoskeletal pain, particularly in patients with poorly healing soft tissue or surgical woundsadjacent to bony structures, in patients with signs of cellulitis overlying previously implantedorthopedic hardware, and in patients with traumatic injury (including bite and puncture wounds). Itshould also be suspected in diabetic patients with ulcers that probe to bone. (See 'Overview' above.)

●

Hematogenous osteomyelitis should be suspected in the setting of new or worseningmusculoskeletal pain, particularly in the setting of fever and/or recent bacteremia. Vertebralosteomyelitis is the most common form of hematogenous osteomyelitis in adults. Issues related tovertebral osteomyelitis are discussed separately. (See 'Overview' above and "Vertebral osteomyelitisand discitis in adults".)

●

In general, the diagnosis of osteomyelitis is established via culture obtained from biopsy of theinvolved bone. A diagnosis of osteomyelitis may be inferred in the following circumstances (see'Overview' above):

●

Clinical and radiographic findings typical of osteomyelitis and positive blood cultures with a likely•

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REFERENCES


2. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeuticconsiderations and unusual aspects. N Engl J Med 1970; 282:198.

3. Mader JT, Shirtliff M, Calhoun JH. Staging and staging application in osteomyelitis. Clin Infect Dis1997; 25:1303.

4. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med 1997; 336:999.

5. Senneville E, Melliez H, Beltrand E, et al. Culture of percutaneous bone biopsy specimens fordiagnosis of diabetic foot osteomyelitis: concordance with ulcer swab cultures. Clin Infect Dis 2006;42:57.

pathogen (such as Staphylococcus aureus); in such cases, bone biopsy is not required but maybe useful, particularly if subsequent therapeutic debridement is needed.

Bone histopathology consistent with osteomyelitis in the absence of positive culture data(particularly in the setting of recent antibiotic administration).

•

Suggestive clinical and typical radiographic findings and persistently elevated inflammatorymarkers, in circumstances with no positive culture data and a biopsy is not feasible.

•

Patients with suspected osteomyelitis should undergo laboratory evaluation (including erythrocytesedimentation rate, C-reactive protein, white blood cell count), blood cultures, and radiographicimaging. In patients with ≥2 weeks of symptoms, conventional radiography is a reasonable initialimaging modality. In patients with <2 weeks of symptoms, an advanced imaging modality (magneticresonance imaging, computed tomography, or nuclear imaging) should be pursued. Advancedimaging is also warranted for patients with diabetes, localized symptoms, and/or abnormal laboratoryresults whose plain radiographs are normal or suggestive of osteomyelitis without characteristicfeatures. Osteomyelitis is unlikely in the absence of radiographic evidence on advanced imaging.(See 'Clinical approach' above.)

●

Findings of osteomyelitis on radiographic imaging should prompt bone biopsy for culture andhistology to confirm the diagnosis and to guide antimicrobial therapy, unless blood cultures arepositive for a likely pathogen (such as S. aureus, a gram-negative enteric rod, or Pseudomonasaeruginosa). (See 'Clinical approach' above.)

●













6. Norden CW. Experimental chronic staphylococcal osteomyelitis in rabbits: treatment with rifampinalone and in combination with other antimicrobial agents. Rev Infect Dis 1983; 5 Suppl 3:S491.

7. Pineda C, Vargas A, Rodríguez AV. Imaging of osteomyelitis: current concepts. Infect Dis ClinNorth Am 2006; 20:789.

8. Ganesh D, Gottlieb J, Chan S, et al. Fungal Infections of the Spine. Spine (Phila Pa 1976) 2015;40:E719.

9. Newman LG, Waller J, Palestro CJ, et al. Unsuspected osteomyelitis in diabetic foot ulcers.Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline. JAMA 1991;266:1246.

10. Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. ClinInfect Dis 2004; 39:885.

11. Butalia S, Palda VA, Sargeant RJ, et al. Does this patient with diabetes have osteomyelitis of thelower extremity? JAMA 2008; 299:806.

12. Grayson ML, Gibbons GW, Balogh K, et al. Probing to bone in infected pedal ulcers. A clinical signof underlying osteomyelitis in diabetic patients. JAMA 1995; 273:721.

13. Álvaro-Afonso FJ, Lázaro-Martínez JL, Aragón-Sánchez FJ, et al. Does the location of the ulceraffect the interpretation of the probe-to-bone test in the diagnosis of osteomyelitis in diabetic footulcers? Diabet Med 2014; 31:112.

14. García Morales E, Lázaro-Martínez JL, Aragón-Sánchez FJ, et al. Inter-observer reproducibility ofprobing to bone in the diagnosis of diabetic foot osteomyelitis. Diabet Med 2011; 28:1238.

15. Lam K, van Asten SA, Nguyen T, et al. Diagnostic Accuracy of Probe to Bone to DetectOsteomyelitis in the Diabetic Foot: A Systematic Review. Clin Infect Dis 2016; 63:944.

16. Senneville E. Editorial Commentary: Probe-to-Bone Test for Detecting Diabetic Foot Osteomyelitis:Rapid, Safe, and Accurate-but for Which Patients? Clin Infect Dis 2016; 63:949.

17. Donlan RM. New approaches for the characterization of prosthetic joint biofilms. Clin Orthop RelatRes 2005; :12.

18. Perry M. Erythrocyte sedimentation rate and C reactive protein in the assessment of suspectedbone infection--are they reliable indices? J R Coll Surg Edinb 1996; 41:116.



































20. Mader JT, Shirtliff M, Calhoun JH. The host and the skeletal infection: classification andpathogenesis of acute bacterial bone and joint sepsis. Baillieres Best Pract Res Clin Rheumatol1999; 13:1.

21. Bhavan KP, Marschall J, Olsen MA, et al. The epidemiology of hematogenous vertebralosteomyelitis: a cohort study in a tertiary care hospital. BMC Infect Dis 2010; 10:158.

22. Chandrasekar PH, Narula AP. Bone and joint infections in intravenous drug abusers. Rev Infect Dis1986; 8:904.

23. Renz N, Haupenthal J, Schuetz MA, Trampuz A. Hematogenous vertebral osteomyelitis associatedwith intravascular device-associated infections - A retrospective cohort study. Diagn Microbiol InfectDis 2017; 88:75.


25. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeuticconsiderations and unusual aspects (second of three parts). N Engl J Med 1970; 282:260.

26. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeuticconsiderations and unusual aspects. 3. Osteomyelitis associated with vascular insufficiency. N EnglJ Med 1970; 282:316.

27. Holzman RS, Bishko F. Osteomyelitis in heroin addicts. Ann Intern Med 1971; 75:693.

28. Gamaletsou MN, Rammaert B, Bueno MA, et al. Aspergillus osteomyelitis: epidemiology, clinicalmanifestations, management, and outcome. J Infect 2014; 68:478.

29. Smith EM, Khan MA, Reingold A, Watt JP. Group B streptococcus infections of soft tissue and bonein California adults, 1995-2012. Epidemiol Infect 2015; 143:3343.

30. Pertuiset E, Beaudreuil J, Lioté F, et al. Spinal tuberculosis in adults. A study of 103 cases in adeveloped country, 1980-1994. Medicine (Baltimore) 1999; 78:309.

31. Garbino J, Schnyder I, Lew D, et al. An unusual cause of vertebral osteomyelitis: Candida species.Scand J Infect Dis 2003; 35:288.

32. Miller DJ, Mejicano GC. Vertebral osteomyelitis due to Candida species: case report and literaturereview. Clin Infect Dis 2001; 33:523.

33. Hendrickx L, Van Wijngaerden E, Samson I, Peetermans WE. Candidal vertebral osteomyelitis:report of 6 patients, and a review. Clin Infect Dis 2001; 32:527.

34. Rolain JM, Chanet V, Laurichesse H, et al. Cat scratch disease with lymphadenitis, vertebral


































osteomyelitis, and spleen abscesses. Ann N Y Acad Sci 2003; 990:397.

35. Caraway NP, Fanning CV, Stewart JM, et al. Coccidioidomycosis osteomyelitis masquerading as abone tumor. A report of 2 cases. Acta Cytol 2003; 47:777.

36. Holley K, Muldoon M, Tasker S. Coccidioides immitis osteomyelitis: a case series review.Orthopedics 2002; 25:827.

37. Do TT, Strub WM, Witte D. Subacute Propionibacterium acnes osteomyelitis of the spine in anadolescent. J Pediatr Orthop B 2003; 12:284.

38. Gordon RJ, Lowy FD. Bacterial infections in drug users. N Engl J Med 2005; 353:1945.

39. Dajer-Fadel WL, Ibarra-Pérez C, Borrego-Borrego R, et al. Descending necrotizing mediastinitisand sternoclavicular joint osteomyelitis. Asian Cardiovasc Thorac Ann 2013; 21:618.

40. Vu TT, Yammine NV, Al-Hakami H, et al. Sternoclavicular joint osteomyelitis following head andneck surgery. Laryngoscope 2010; 120:920.


42. Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin OrthopRelat Res 2003; :7.

43. Miller WB Jr, Murphy WA, Gilula LA. Brodie abscess: reappraisal. Radiology 1979; 132:15.

44. Ogbonna OH, Paul Y, Nabhani H, Medina A. Brodie's Abscess in a Patient Presenting with SickleCell Vasoocclusive Crisis. Case Rep Med 2015; 2015:429876.

45. Gould CF, Ly JQ, Lattin GE Jr, et al. Bone tumor mimics: avoiding misdiagnosis. Curr Probl DiagnRadiol 2007; 36:124.

46. Buldu H, Bilen FE, Eralp L, Kocaoglu M. Bilateral Brodie's abscess at the proximal tibia. SingaporeMed J 2012; 53:e159.

47. Mujer MT, Rai MP, Hassanein M, Mitra S. Emphysematous Osteomyelitis. BMJ Case Rep 2018;2018.

48. Luey C, Tooley D, Briggs S. Emphysematous osteomyelitis: a case report and review of theliterature. Int J Infect Dis 2012; 16:e216.

49. Larsen J, Mühlbauer J, Wigger T, Bardosi A. Emphysematous osteomyelitis. Lancet Infect Dis2015; 15:486.

50. Gelfand MS, Cleveland KO, Heck RK, Goswami R. Pathological fracture in acute osteomyelitis oflong bones secondary to community-acquired methicillin-resistant Staphylococcus aureus: two

































cases and review of the literature. Am J Med Sci 2006; 332:357.

51. Altay M, Arikan M, Yildiz Y, Saglik Y. Squamous cell carcinoma arising in chronic osteomyelitis infoot and ankle. Foot Ankle Int 2004; 25:805.

52. Akbarnia BA, Wirth CR, Colman N. Fibrosarcoma arising from chronic osteomyelitis. Case reportand review of the literature. J Bone Joint Surg Am 1976; 58:123.

53. Bacchini P, Calderoni P, Gherlinzoni F, Gualtieri G. Angiosarcoma in chronic osteomyelitis. Ital JOrthop Traumatol 1984; 10:393.

54. Campanacci M. Carcinomas and sarcomas on chronic osteomyelitis. In: Bone and Soft Tissue Tumors, Springer-Verlag Wien, 1990. p.661.

55. Czerwiński E, Skolarczyk A, Frasik W. Malignant fibrous histiocytoma in the course of chronicosteomyelitis. Arch Orthop Trauma Surg 1991; 111:58.

56. Johnston RM, Miles JS. Sarcomas arising from chronic osteomyelitic sinuses. A report of twocases. J Bone Joint Surg Am 1973; 55:162.

57. Kennedy C, Stoker DJ. Malignant fibrous histiocytoma complicating chronic osteomyelitis. ClinRadiol 1990; 41:435.

58. McGrory JE, Pritchard DJ, Unni KK, et al. Malignant lesions arising in chronic osteomyelitis. ClinOrthop Relat Res 1999; :181.

59. Nolla JM, Ariza J, Gómez-Vaquero C, et al. Spontaneous pyogenic vertebral osteomyelitis innondrug users. Semin Arthritis Rheum 2002; 31:271.

60. Patzakis MJ, Rao S, Wilkins J, et al. Analysis of 61 cases of vertebral osteomyelitis. Clin OrthopRelat Res 1991; :178.

61. White LM, Schweitzer ME, Deely DM, Gannon F. Study of osteomyelitis: utility of combinedhistologic and microbiologic evaluation of percutaneous biopsy samples. Radiology 1995; 197:840.

62. Howard CB, Einhorn M, Dagan R, et al. Fine-needle bone biopsy to diagnose osteomyelitis. J BoneJoint Surg Br 1994; 76:311.

63. Wheat J. Diagnostic strategies in osteomyelitis. Am J Med 1985; 78:218.

64. Senneville E, Morant H, Descamps D, et al. Needle puncture and transcutaneous bone biopsycultures are inconsistent in patients with diabetes and suspected osteomyelitis of the foot. ClinInfect Dis 2009; 48:888.

65. Darouiche RO, Landon GC, Klima M, et al. Osteomyelitis associated with pressure sores. ArchIntern Med 1994; 154:753.


































66. Perry CR, Pearson RL, Miller GA. Accuracy of cultures of material from swabbing of the superficialaspect of the wound and needle biopsy in the preoperative assessment of osteomyelitis. J BoneJoint Surg Am 1991; 73:745.


68. Khatri G, Wagner DK, Sohnle PG. Effect of bone biopsy in guiding antimicrobial therapy forosteomyelitis complicating open wounds. Am J Med Sci 2001; 321:367.

69. Zuluaga AF, Galvis W, Jaimes F, Vesga O. Lack of microbiological concordance between bone andnon-bone specimens in chronic osteomyelitis: an observational study. BMC Infect Dis 2002; 2:8.

70. Mackowiak PA, Jones SR, Smith JW. Diagnostic value of sinus-tract cultures in chronicosteomyelitis. JAMA 1978; 239:2772.

71. Trampuz A, Piper KE, Hanssen AD, et al. Sonication of explanted prosthetic components in bagsfor diagnosis of prosthetic joint infection is associated with risk of contamination. J Clin Microbiol2006; 44:628.

72. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee prostheses fordiagnosis of infection. N Engl J Med 2007; 357:654.

73. Anderson's Pathology, 10th ed, Danjanov I, Linder J (Eds), Mosby Yearbook, 1996. p.2605.

74. Shimose S, Sugita T, Kubo T, et al. Differential diagnosis between osteomyelitis and bone tumors.Acta Radiol 2008; 49:928.

75. Seybold U, Talati NJ, Kizilbash Q, et al. Hematogenous osteomyelitis mimicking osteosarcoma dueto Community Associated Methicillin-Resistant Staphylococcus aureus. Infection 2007; 35:190.
























GRAPHICS

Cierny-Mader staging system for long-bone osteomyelitis

Anatomic type

Stage 1: Medullary osteomyelitis

Medullary osteomyelitis denotes infection confined to the intramedullary surfaces of the bone. Hematogenous osteomyelitisand infected intramedullary rods are examples of this anatomic type.

Stage 2: Superficial osteomyelitis

Superficial osteomyelitis is a true contiguous focus infection of bone; it occurs when an exposed infected necrotic surfaceof bone lies at the base of a soft-tissue wound.

Stage 3: Localized osteomyelitis

Localized osteomyelitis is usually characterized by a full thickness, cortical sequestration, which can be removed surgicallywithout compromising bony stability.

Stage 4: Diffuse osteomyelitis

Diffuse osteomyelitis is a through-and-through process that usually requires an intercalary resection of the bone to arrestthe disease process. Diffuse osteomyelitis includes those infections with a loss of bony stability either before or afterdebridement surgery.

Physiologic class of host*

Class A denotes a normal host

Class B denotes a host with systemic compromise, local compromise, or both

Class C denotes a host for whom the morbidity of treatment is worse than that imposed by the disease itself

Factors affecting immune surveillance, metabolism, and local vascularity

Systemic factors Local factors

Malnutrition Chronic lymphedema

Renal or hepatic failure Venous stasis

Diabetes mellitus Major vessel compromise

Chronic hypoxia Arteritis

Immune disease Small vessel disease

Malignancy Extensive scarring

Extremes of age Radiation fibrosis

Immunosuppression or immune deficiency Neuropathy

Tobacco abuse (≥2 packs per day)

* Host factors are important for prognosticating containment of infection. A systemically and/or locally compromised host cannotisolate an infectious focus as well as a normal host, so treatment of osteomyelitis is more difficult in such patients.

Adapted from: Cierny G, Mader JT, Pennick JJ. A clinical staging system for adult osteomyelitis. Contemp Orthop 1985; 10:17.









Tahaniyat Lalani, MBBS, MHS Nothing to disclose Steven K Schmitt, MD, FIDSA Nothing to disclose DenisSpelman, MBBS, FRACP, FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose




Osteomyelitis in adults: Treatment - UpToDate



Osteomyelitis in adults: TreatmentAuthors: Douglas R Osmon, MD, Aaron J Tande, MD Section Editor: Denis Spelman, MBBS, FRACP, FRCPA, MPH DeputyEditor: Elinor L Baron, MD, DTMH


Literature review current through: Feb 2020. | This topic last updated: May 10, 2019.

INTRODUCTION

Treatment of osteomyelitis includes consideration of issues related to debridement, management ofinfected foreign bodies (if present), antibiotic selection, and duration of therapy; these issues arediscussed in the following sections.

General issues related to treatment of osteomyelitis are discussed here. Issues related to clinicalmanifestations and diagnosis of osteomyelitis are discussed separately. (See "Osteomyelitis in adults:Clinical manifestations and diagnosis".)

Issues related to treatment of vertebral osteomyelitis, osteomyelitis associated with trauma, pelvic andsacral osteomyelitis, and prosthetic joint infection are discussed in detail separately. (See "Vertebralosteomyelitis and discitis in adults" and "Osteomyelitis associated with open fractures in adults" and"Pelvic osteomyelitis and other infections of the bony pelvis in adults" and "Prosthetic joint infection:Treatment".)

Issues related to osteomyelitis in children are presented separately. (See "Hematogenous osteomyelitisin children: Evaluation and diagnosis" and "Hematogenous osteomyelitis in children: Management".)

CLINICAL APPROACH

Nonhematogenous osteomyelitis

Absence of orthopedic hardware — In general, management of osteomyelitis (in the absence oforthopedic hardware) consists of operative debridement followed by antimicrobial therapy for eradicationof infection.

There may be a role for antimicrobial therapy alone (in the absence of surgical debridement) for carefullyselected patients with diabetic foot osteomyelitis. In observational studies, success rates for treatment of

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diabetic foot osteomyelitis with antimicrobial therapy alone range from 64 to 82 percent [1-3]. In one smallrandomized trial including 37 patients treated with antibiotics alone for three months or surgicaldebridement and antibiotics for ten days, there was no difference in healing between the two groups [4].However, patients with common comorbid conditions (such as arterial disease, Charcot arthropathy, andpoorly controlled diabetes) were excluded.

Surgical debridement — Surgical debridement for management of osteomyelitis consists ofremoval of necrotic material and culture of involved tissue and bone. A satisfactory soft tissue envelopeoverlying the site of infection must be re-established for successful treatment, either via direct closure orflap coverage.

In the setting of dead or injured bone and/or infected fluid collections, surgical debridement (andrevascularization, in some cases) is a cornerstone of therapy. Antimicrobial therapy alone is not effectivefor cure of infected, necrotic bone. In addition, antibiotic penetration into bone may be unreliable inpatients with arterial insufficiency or prior scarring associated with trauma [5].

Surgical debridement also allows placement of local antimicrobials, either applied directly to the site ofinfection or mixed with absorbable (eg, calcium sulfate) or nonabsorbable (eg, polymethyl methacrylatecement) carriers. (See "Management of diabetic foot ulcers" and "Osteomyelitis associated with openfractures in adults".)

Patients who have received antibiotics recently and do not have an acute need for surgical interventionshould discontinue antibiotics for at least two weeks prior to debridement to optimize microbiologicdiagnosis. However, patients with necrotizing soft tissue infection or with systemic infection secondary toosteomyelitis in whom source control is needed should undergo early surgical debridement.

Antibiotic therapy — The clinical approach to antibiotic therapy is discussed in this section; issuesrelated to selection of antibiotic therapy are discussed below. (See 'Antibiotic therapy' below.)

Residual infected bone present — Patients with residual infected bone that is not amenable tocomplete removal should be treated with a prolonged duration of intravenous or highly bioavailable oralantibiotic therapy, guided by antimicrobial susceptibility data (table 1). (See 'Antibiotic therapy' below.)

The optimal duration of antibiotic therapy for treatment of osteomyelitis with residual infected bone isuncertain. Most experts favor continuing antimicrobial therapy at least until debrided bone has beencovered by vascularized soft tissue, which is usually at least six weeks from the last debridement [6].Parenteral antimicrobial therapy can be administered on an outpatient basis via a peripherally insertedcentral catheter or similar device. In some circumstances, highly bioavailable oral antibiotic therapy maybe administered.

While on parenteral antimicrobial therapy, patients should have weekly bloodwork for safety monitoring.(See 'Laboratory monitoring' below.)

No residual infected bone — Patients who undergo amputation or complete removal of all

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involved bone warrant a relatively short course of antibiotic therapy (table 1). In the absence ofconcomitant soft tissue infection, antibiotic therapy may be discontinued as early as two to five days afterdebridement. When there is evidence of soft tissue infection at the operative site, 10 to 14 days ofpathogen-directed parenteral or highly bioavailable oral therapy is reasonable [5].

Presence of orthopedic hardware

Surgical debridement — In general, the approach to management of osteomyelitis associatedwith orthopedic hardware consists of operative debridement, obtaining bone biopsy for culture, andantimicrobial therapy tailored to culture and susceptibility data [7-9]. The need for hardware to maintainbone stability must be balanced with the potential impact of foreign material on propagation of infection.Additional factors influencing the approach include the microbiology of infection and individual patientcircumstances.

Surgical management strategies include debridement with hardware retention or debridement withhardware removal. Hardware retention may be attempted when the stability of the bone and hardwareconstruct would be compromised (such as in the case of fracture fixation hardware with unhealedfracture) or when there is a clear anatomic separation between the osteomyelitis and hardware. Incontrast, hardware should be removed if the hardware is no longer needed for bone stability or ifadequate debridement of the infected bone cannot be achieved with hardware retention.

Antibiotic therapy — The clinical approach to antibiotic therapy is discussed in this section; issuesrelated to selection of antibiotic therapy are discussed below. (See 'Antibiotic therapy' below.)

Retained hardware — Patients with orthopedic hardware that is not amenable to removaland/or residual involved bone that is not amenable to complete debridement should be treated with aprolonged duration of intravenous antibiotic therapy (table 1). The optimal duration is uncertain; mostexperts favor six weeks of therapy. While on parenteral antimicrobial therapy, patients should haveweekly bloodwork for safety monitoring. (See 'Laboratory monitoring' below.)

Following completion of parenteral therapy with resolution of clinical signs of acute infection, patients withretained hardware and/or necrotic bone not amenable to debridement should receive long-term antibioticsuppression with an oral agent, guided by antimicrobial susceptibility data. Regimens for antibioticsuppression are summarized in the table (table 2).

In general, oral antimicrobial suppression should be continued until fractures are united. Once fracturehealing is demonstrated radiographically, the timeframe for discontinuation of oral antimicrobialsuppression should be determined carefully. Factors influencing the duration of therapy include themicrobiology of infection, the duration of infection prior to debridement, the tolerability of the antimicrobialsuppression regimen, the status of the orthopedic hardware (if present) at the site of infection, andindividual patient circumstances.

Patients who would be unable to tolerate additional surgery in the setting of relapse may warrantantimicrobial suppression for as long as the hardware remains in place. However, the benefit of








continuing suppressive treatment for longer than six months is uncertain. In one observational studyincluding 89 patients with retained orthopedic hardware, use of suppressive antibiotics for at least threemonths after diagnosis was associated with being free of clinical infection (odds ratio 3.5; 95% CI 1.3-9.4), but use of suppressive antibiotic for at least six months after diagnosis was not [10].

Among patients who remain on antimicrobial suppression after fracture union, we discuss with the patientthe benefits and adverse effects of ongoing suppression compared with discontinuing suppression. Ifhardware removal could be performed in the event of infection relapse (such as healed long-bonefracture), the infection appears to be well suppressed, and the patient is comfortable with the smallpossibility of further surgery, we offer discontinuation of suppression. If this small possibility of surgery isunacceptable, we continue suppression indefinitely.

No retained hardware — Patients with no retained hardware should complete a prolongedduration of intravenous antibiotic therapy (table 1). Most experts favor continuing antimicrobial therapy atleast until debrided bone has been covered by vascularized soft tissue, which is usually at least sixweeks from the last debridement.

While on parenteral antimicrobial therapy, patients should have weekly bloodwork for safety monitoring.(See 'Laboratory monitoring' below.)

Laboratory monitoring — Laboratory monitoring is needed during prolonged administration ofantimicrobial therapy to monitor for adverse drug effects and to assess control of infection.

For patients on parenteral antimicrobial therapy, we obtain weekly complete blood count and chemistries.We obtain serum inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) at thebeginning and end of parenteral therapy and at the time of transition to oral suppressive therapy (if used).

We do not routinely monitor weekly serum inflammatory markers during parenteral antimicrobial therapy.However, if there is clinical suspicion for treatment failure, we use inflammatory markers (in conjunctionwith clinical examination and radiographic studies such as magnetic resonance imaging or plainradiograph) to guide further management. (See 'Persistently elevated inflammatory markers' below.)

For patients on oral suppressive antimicrobial therapy, we obtain a complete blood count, creatinine, andalanine aminotransferase at 2, 4, 8, and 12 weeks and then every 6 to 12 months thereafter.

Persistently elevated inflammatory markers — In the setting of persistently elevated inflammatorymarkers after completing a course of antibiotic therapy, the first priority should be to ensure that athorough and complete debridement has been performed. In addition, the microbiologic diagnosis andsusceptibility data should be reviewed.

Persistently elevated inflammatory markers two weeks following completion of antimicrobial therapy(without an alternative explanation) should prompt concern for persistent osteomyelitis [11,12]. Patientswith associated symptoms warrant repeat debridement and additional antimicrobial therapy. In theabsence of clinical signs consistent with persistent infection, clinical observation may be reasonable.



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Hematogenous (nonvertebral) osteomyelitis — In adults, hematogenous osteomyelitis mostcommonly involves the vertebral bones. Issues related to vertebral osteomyelitis are discussedseparately. (See "Vertebral osteomyelitis and discitis in adults".)

Treatment of hematogenous (nonvertebral) osteomyelitis consists of parenteral antibiotics; in somecircumstances, surgical debridement is also warranted.

In general, patients with infection confined to the medullary canal of the bone may be treated withantibiotics alone. Surgical debridement is warranted in patients with subperiosteal collection or abscess,necrotic bone, and/or in the setting of concomitant joint infection. Depending on the scope of thedebridement, bone grafting or other orthopedic reconstruction may be required. A critical component ofsurgical management is adequate soft tissue coverage.

In all patients, blood cultures should be obtained prior to initiation of antibiotic therapy. If blood culturesare negative, a bone biopsy or aspirate of subperiosteal abscess for culture should be performed.

Empiric antibiotic coverage for treatment of hematogenous osteomyelitis should include activity againstmethicillin-resistant Staphylococcus aureus and aerobic gram-negative bacilli. An appropriate regimenconsists of vancomycin and a third- or fourth-generation cephalosporin (table 1).

Once an etiologic organism is isolated, the antibiotic regimen should be tailored to susceptibility data [13].

The optimal duration of antibiotic therapy for treatment of hematogenous (nonvertebral) osteomyelitis isuncertain. In general, at least four weeks of parenteral therapy from the last major debridement (ifperformed) are warranted.

For patients on parenteral antimicrobial therapy, we obtain weekly complete blood count and chemistries.In addition, we obtain serum inflammatory markers (erythrocyte sedimentation rate and C-reactiveprotein) at the beginning and end of parenteral therapy and at the time of transition to oral suppressivetherapy (if used).

ANTIBIOTIC THERAPY

Whenever possible, initiation of antibiotic therapy should be delayed until bone cultures can be obtained.Patients who have received antibiotics recently and do not have an acute need for surgical interventionshould discontinue antibiotics for at least two weeks prior to debridement to optimize microbiologicdiagnosis.

Suggested antibiotic regimens are outlined in the table (table 1)[14-19]. Antibiotic therapy should betailored to culture and susceptibility findings when available.

Systemic therapy — Management of complex orthopedic infections usually includes a prolonged courseof intravenous (IV) antibiotic therapy; data regarding use of oral antibiotic therapy are emerging.


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In one randomized trial including more than 1000 patients with bone or joint infection treated with IV ororal antibiotic therapy for at least six weeks (median duration of therapy 78 and 71 days, respectively),the rates of treatment failure within one year were comparable (14 versus 13 percent) [20]. A variety oforthopedic infections were included, including osteomyelitis with or without an associated implant;surgical debridement occurred in 92 percent of cases. Based on these data, among carefully selectedpatients who undergo surgical debridement and have infection caused by an organism that is susceptibleto oral therapy, a course of oral antimicrobial therapy (preferably with highly bioavailable agents, perhapswith extended duration up 12 weeks) may be a reasonable consideration in some circumstances.However, the generalizability of these findings is limited by the heterogeneous patient population andopen-label design, so the results should be interpreted carefully when applied to individual patients.

Empiric therapy — Empiric treatment of osteomyelitis should consist of antimicrobial therapy withactivity against methicillin-resistant S. aureus (MRSA) and gram-negative organisms. Reasonableregimens include vancomycin in combination with a third- or fourth-generation cephalosporin. We avoidcombined use of vancomycin with piperacillin-tazobactam, given the risk of nephrotoxicity with thiscombination [21]. Antibiotic therapy should be tailored to culture and susceptibility data when available.

Definitive therapy

Staphylococci

Staphylococcus aureus — In general, definitive therapy for treatment of osteomyelitis due to S.aureus consists of parenteral antibiotic therapy; regimens are summarized in the table (table 1). Inaddition, use of adjunctive agents for treatment of S. aureus osteomyelitis may be warranted in somecircumstances. (See 'Use of adjunctive agents' below.)

Antibiotics for treatment of osteomyelitis due to methicillin-susceptible S. aureus (MSSA) includeoxacillin, nafcillin, and cefazolin (table 1). Use of ceftriaxone for treatment of staphylococcal osteomyelitisis not universally accepted; in our practice, we use it as an alternative regimen for isolates with oxacillinminimum inhibitory concentration <0.5 mcg/mL in the absence of concomitant bacteremia, since once-daily dosing is a convenient outpatient regimen [22,23]. Issues related to duration of antibiotic therapy arediscussed above. (See 'Clinical approach' above.)

The antibiotic of choice for treatment of osteomyelitis due to MRSA is vancomycin (table 1); it is theantibiotic agent for which there is the greatest cumulative clinical experience, although there are nocontrolled trials [24,25]. The Infectious Diseases Society of America (IDSA) guidelines recommend aminimum of eight weeks of antibiotic therapy for treatment of MRSA osteomyelitis [24]; we favor a six-week course of therapy if adequate debridement has been performed. (See 'Clinical approach' above.)

Acceptable alternative agents to vancomycin for treatment of osteomyelitis due to MRSA includedaptomycin (and teicoplanin, where available) [26-28]. An observational study including more than 400patients with osteomyelitis due to gram-positive pathogens noted success rates of 80 percent withdaptomycin for treatment of staphylococcal osteomyelitis [28]. The optimal dosing of daptomycin for



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treatment of osteomyelitis is uncertain; dosing used in the preceding study ranged from 6 to 10mg/kg/day.

Antibiotic agents that warrant further study for treatment of staphylococcal osteomyelitis includeceftaroline, telavancin, and dalbavancin [29-35]. Ceftaroline has been used successfully for treatment ofosteomyelitis but has been associated with increased risk of neutropenia [30,36]. Pending further study,use of ceftaroline should be reserved for patients unable to receive other therapies [30]. Ceftarolinesusceptibility must be confirmed; the prevalence of resistance is high in some regions [37]. Use oftelavancin for treatment of osteomyelitis should be deferred pending further study to evaluate safety,given increased risk of adverse events observed with its use for treatment of other conditions [29,31,38].Dalbavancin has the unique advantage of weekly intravenous dosing [32]. It has been used successfullyfor treatment of osteomyelitis, but should be reserved for use in patients in whom other therapies are notan option and in whom the organism is susceptible, until further data are available [32-35].

We do not favor use of trimethoprim-sulfamethoxazole, linezolid, tedizolid, clindamycin, fluoroquinolones,quinupristin-dalfopristin, or tigecycline for definitive therapy of osteomyelitis due to S. aureus. A regimenof trimethoprim-sulfamethoxazole with rifampin is advocated in some treatment guidelines [24] but notothers [39]; data to support its use are limited [12,40,41]. Prolonged use of linezolid is limited by bonemarrow toxicity, peripheral and optic neuropathy, lactic acidosis, and drug-drug interactions [42-44].Tedizolid has not been studied sufficiently in osteomyelitis. Prolonged use of clindamycin has beenassociated with antibiotic-associated diarrhea and Clostridioides (formerly Clostridium) difficile infection.Fluoroquinolones have good bone penetration but are associated with inducible resistance to S. aureuswhen used as monotherapy.

Coagulase-negative staphylococci — Most coagulase-negative staphylococci are methicillinresistant (an exception is Staphylococcus lugdunensis, which is almost universally methicillinsusceptible). (See "Staphylococcus lugdunensis".)

Empiric treatment for osteomyelitis due to coagulase-negative staphylococci should consists of an agentwith activity against methicillin-resistant staphylococci. If susceptibility testing demonstrates methicillinsusceptibility, a beta-lactam with activity against methicillin-susceptible staphylococci should be used(table 1).

In addition, use of adjunctive agents for treatment staphylococcal osteomyelitis may be warranted insome circumstances. (See 'Use of adjunctive agents' below.)

Use of adjunctive agents — Agents that may be used adjunctively in the setting of definitivetherapy for treatment of staphylococcal osteomyelitis include rifampin and fusidic acid.

We are in agreement with some experts who favor use of rifampin (in combination with at least one otheranti-staphylococcal agent) for its activity against microorganisms in biofilms, given the importance ofbiofilms in the pathophysiology of staphylococcal osteomyelitis (particularly in the setting of hardware)[24,45,46]. However, others oppose use of adjunctive rifampin given limited evidence for improved

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outcomes over standard antimicrobial therapy.

Clinical circumstances in which rifampin may be most useful include osteomyelitis in the setting ofprosthetic material and osteomyelitis in which therapeutic options are limited. Data may be extrapolatedfrom literature on treatment of prosthetic joint infection to support use of rifampin in the treatment ofinfections involving other types of orthopedic hardware [47,48]. Use of rifampin must be weighed againstthe likelihood of toxicity and drug interactions [49]. (See "Prosthetic joint infection: Treatment", section on'Debridement and retention of prosthesis'.)

Rifampin must be combined with another active antibacterial agent because rapid emergence ofresistance in the setting of rifampin monotherapy is common. Rifampin should be initiated several daysafter surgical debridement; resistance is less likely to emerge when the burden of organisms has beenreduced [46,50]. We continue rifampin for the duration of definitive therapy (parenteral therapy or highlybioavailable oral antibiotic therapy). [46]. We do not use rifampin during suppressive therapy. (See"Rifamycins (rifampin, rifabutin, rifapentine)" and "Prosthetic joint infection: Treatment".)

Fusidic acid (not available in the United States) may be used as adjunctive oral therapy in the treatmentof chronic osteomyelitis [51-53].

Gram-negative organisms — For treatment of osteomyelitis due to gram-negative organisms, wefavor fluoroquinolones (if susceptibility testing confirms sensitivity) since they have high bone penetrationwith oral administration [19,54]. However, some avoid use of these agents in the setting of fracture, dueto possible adverse effects on fracture healing [54].

Other antibiotics for treatment of osteomyelitis due to gram-negative organisms include parenteral beta-lactams and carbapenems. Antibiotic dosing is summarized in the table (table 1).

Among the gram-negative organisms, management of osteomyelitis caused by Pseudomonasaeruginosa may be more difficult than other organisms [55,56]. In one cohort study including 66 patientswith osteomyelitis due to P. aeruginosa who underwent surgical debridement, most patients were treatedwith two weeks of intravenous therapy followed by oral fluoroquinolone therapy (median duration oftreatment 45 days); clearance of infection was demonstrated in 94 percent of cases [56]. Most patientsreceived monotherapy; no emergence of resistance was observed.

Streptococci and enterococci — Osteomyelitis due to penicillin-susceptible streptococci may betreated with penicillin; ceftriaxone is also acceptable and is more convenient for outpatient administration(table 1).

For treatment of osteomyelitis due to enterococci, it is unclear whether combination therapy is superior tomonotherapy, particularly if thorough debridement is performed [57]. We favor combination therapy in thesetting of retained hardware; the regimen of ampicillin and ceftriaxone is generally well tolerated [58].However, if antibiotic-impregnated material containing gentamicin is implanted at the time ofdebridement, monotherapy is likely sufficient; in such cases, we favor treatment with intravenousampicillin or penicillin (table 1).




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Suppressive therapy — Long-term antibiotic suppression with an oral agent is warranted for patientswith retained hardware and/or necrotic bone not amenable to debridement, following completion ofparenteral therapy with resolution of clinical signs of acute infection. (See 'Retained hardware' above.)

Duration of therapy — Issues related to duration of antibiotic therapy are discussed above. (See'Clinical approach' above.)

Local antibiotic delivery — Local antimicrobials mixed with absorbable carriers (eg, calcium sulfatebeads) or nonabsorbable carriers (eg, polymethyl methacrylate beads or cement) placed in and aroundthe fracture site may be useful as an adjunct to systemic antibiotics for prevention or treatment ofinfection [59].

Data are most robust for polymethylmethacrylate beads; these are typically removed within two to fourweeks. Antibiotic-impregnated calcium sulfate beads are absorbable; they have been used as a bonesubstitute and delivery system for antibiotics repairing bony defects in open fractures caused by combat-related injuries [59,60].

SPECIAL POPULATIONS

Osteomyelitis associated with trauma — Issues related to osteomyelitis associated with trauma arediscussed separately. (See "Osteomyelitis associated with open fractures in adults".)

Prosthetic joint infection — Issues related to prosthetic joint infection are discussed separately. (See"Prosthetic joint infection: Treatment".)

Osteomyelitis in sickle cell disease — Issues related to osteomyelitis in sickle cell disease arediscussed separately. (See "Acute and chronic bone complications of sickle cell disease", section on'Osteomyelitis and septic arthritis'.)

ADJUNCTIVE THERAPIES

Hyperbaric oxygen (HBO) has been suggested as an adjunctive therapy in patients with refractoryosteomyelitis [61,62]. We do not favor use of HBO for treatment of osteomyelitis, given lack of sufficientdata.

Issues related to HBO are discussed further separately. (See "Hyperbaric oxygen therapy".)

OUTCOME

Success rates for treatment of osteomyelitis reported in the literature range from 60 to 90 percent [12].The success rate can be highly variable given the heterogeneity in completeness of debridement, the








https://www.uptodate.com/contents/hyperbaric-oxygen-therapy?search=osteomyelitis&topicRef=114350&source=see_link




possibility of concomitant vascular insufficiency at the site of infection, heterogeneity in completeness ofdebridement, and other factors.


Links to society and government-sponsored guidelines from selected countries and regions around theworld are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infection inadults" and "Society guideline links: Outpatient parenteral antimicrobial therapy".)


In general, management of nonhematogenous osteomyelitis consists of operative debridement forremoval of necrotic material and culture of involved tissue and bone, followed by antimicrobialtherapy for eradication of infection. (See 'Nonhematogenous osteomyelitis' above.)

●

In the absence of orthopedic hardware (see 'Absence of orthopedic hardware' above):•

Patients with residual infected bone that is not amenable to complete removal should betreated with a prolonged duration antibiotic therapy, guided by antimicrobial susceptibilitydata (table 1). The optimal duration of antibiotic therapy is uncertain; we favor continuingantimicrobial therapy at least six weeks from the last debridement. (See 'Residual infectedbone present' above.)

-

Patients who undergo amputation or complete removal of all involved bone warrant arelatively short course of antibiotic therapy. (See 'No residual infected bone' above.)

-

In the presence of orthopedic hardware (see 'Presence of orthopedic hardware' above):•

Following debridement, patients should be treated with a prolonged duration of intravenousantibiotic therapy, guided by antimicrobial susceptibility data (table 1). The optimal durationis uncertain; we favor six weeks of therapy. (See 'No retained hardware' above.)

-

Thereafter, patients with retained hardware and/or necrotic bone not amenable todebridement should receive long-term antibiotic suppression with an oral agent, guided byantimicrobial susceptibility data (table 2). (See 'Retained hardware' above.)

-

Empiric treatment of nonhematogenous osteomyelitis should consist of antimicrobial therapy withactivity against methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative organisms.Reasonable regimens include vancomycin in combination with a third- or fourth-generationcephalosporin. (See 'Empiric therapy' above.)

●

For treatment of osteomyelitis due to MRSA, we suggest vancomycin (Grade 2C); daptomycin is anacceptable alternative agent (table 1). (See 'Staphylococcus aureus' above.)

●



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https://www.uptodate.com/contents/grade/6?title=Grade%202C&topicKey=ID/114350





ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Tahaniyat Lalani, MBBS, MHS, whocontributed to an earlier version of this topic review.


REFERENCES

1. Game FL, Jeffcoate WJ. Primarily non-surgical management of osteomyelitis of the foot in diabetes.Diabetologia 2008; 51:962.

2. Senneville E, Lombart A, Beltrand E, et al. Outcome of diabetic foot osteomyelitis treatednonsurgically: a retrospective cohort study. Diabetes Care 2008; 31:637.

3. Tone A, Nguyen S, Devemy F, et al. Six-week versus twelve-week antibiotic therapy fornonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomizedstudy. Diabetes Care 2015; 38:302.

4. Lázaro-Martínez JL, Aragón-Sánchez J, García-Morales E. Antibiotics versus conservative surgeryfor treating diabetic foot osteomyelitis: a randomized comparative trial. Diabetes Care 2014; 37:789.


6. Guglielmo BJ, Luber AD, Paletta D Jr, Jacobs RA. Ceftriaxone therapy for staphylococcalosteomyelitis: a review. Clin Infect Dis 2000; 30:205.

For patients with S. aureus osteomyelitis and retained hardware, we suggest adjunctive use ofrifampin (in combination with at least one other anti-staphylococcal agent) (Grade 2C). Use ofrifampin must be weighed against the likelihood of toxicity and drug interactions. (See 'Use ofadjunctive agents' above.)

●

Treatment of hematogenous (nonvertebral) osteomyelitis consists of parenteral antibiotic therapy. Inaddition, surgical debridement is warranted in the setting of subperiosteal collection and/or in thesetting of concomitant joint infection. Empiric antibiotic coverage for treatment of hematogenousosteomyelitis should include activity against MRSA and aerobic gram-negative bacilli. Once anetiologic organism is isolated, the antibiotic regimen should be tailored to susceptibility data. Theoptimal duration of antibiotic therapy is uncertain; in general, at least four weeks of parenteraltherapy from the last major debridement are warranted. (See 'Hematogenous (nonvertebral)osteomyelitis' above.)

●















https://www.uptodate.com/contents/grade/6?title=Grade%202C&topicKey=ID/114350



7. Trampuz A, Zimmerli W. Diagnosis and treatment of infections associated with fracture-fixationdevices. Injury 2006; 37 Suppl 2:S59.

8. Weber EJ. Plantar puncture wounds: a survey to determine the incidence of infection. J AccidEmerg Med 1996; 13:274.

9. Roesgen M, Hierholzer G, Hax PM. Post-traumatic osteomyelitis. Pathophysiology andmanagement. Arch Orthop Trauma Surg 1989; 108:1.

10. Keller SC, Cosgrove SE, Higgins Y, et al. Role of Suppressive Oral Antibiotics in OrthopedicHardware Infections for Those Not Undergoing Two-Stage Replacement Surgery. Open ForumInfect Dis 2016; 3:ofw176.

11. Dombrowski JC, Winston LG. Clinical failures of appropriately-treated methicillin-resistantStaphylococcus aureus infections. J Infect 2008; 57:110.

12. Spellberg B, Lipsky BA. Systemic antibiotic therapy for chronic osteomyelitis in adults. Clin InfectDis 2012; 54:393.

13. Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an international collaborative study.Acta Pathol Microbiol Scand B Microbiol Immunol 1971; 217:Suppl 217:1+.

14. Mader JT, Cantrell JS, Calhoun J. Oral ciprofloxacin compared with standard parenteral antibiotictherapy for chronic osteomyelitis in adults. J Bone Joint Surg Am 1990; 72:104.

15. Davey PG, Rowley DR, Phillips GA. Teicoplanin--home therapy for prosthetic joint infections. Eur JSurg Suppl 1992; :23.

16. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from30 years of clinical trials? Int J Infect Dis 2005; 9:127.

17. Black J, Hunt TL, Godley PJ, Matthew E. Oral antimicrobial therapy for adults with osteomyelitis orseptic arthritis. J Infect Dis 1987; 155:968.

18. Gentry LO, Rodriguez-Gomez G. Ofloxacin versus parenteral therapy for chronic osteomyelitis.Antimicrob Agents Chemother 1991; 35:538.

19. Lew DP, Waldvogel FA. Quinolones and osteomyelitis: state-of-the-art. Drugs 1995; 49 Suppl2:100.

20. Li HK, Rombach I, Zambellas R, et al. Oral versus Intravenous Antibiotics for Bone and JointInfection. N Engl J Med 2019; 380:425.

21. Luther MK, Timbrook TT, Caffrey AR, et al. Vancomycin Plus Piperacillin-Tazobactam and AcuteKidney Injury in Adults: A Systematic Review and Meta-Analysis. Crit Care Med 2018; 46:12.


































22. Wieland BW, Marcantoni JR, Bommarito KM, et al. A retrospective comparison of ceftriaxoneversus oxacillin for osteoarticular infections due to methicillin-susceptible Staphylococcus aureus.Clin Infect Dis 2012; 54:585.

23. Sharff K, Graber CJ, Spindel SJ, Nguyen HM. Ceftriaxone for Methicillin-Sensitive Staphylococcusaureus Osteoarticular Infections: A Survey of Infectious Disease Physicians’ Attitudes and Reviewof the Literature. Infect Dis Clin Pract (Baltim Md) 2014; 22:132.

24. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society ofamerica for the treatment of methicillin-resistant Staphylococcus aureus infections in adults andchildren. Clin Infect Dis 2011; 52:e18.

25. Darley ES, MacGowan AP. Antibiotic treatment of gram-positive bone and joint infections. JAntimicrob Chemother 2004; 53:928.

26. Lalani T, Boucher HW, Cosgrove SE, et al. Outcomes with daptomycin versus standard therapy forosteoarticular infections associated with Staphylococcus aureus bacteraemia. J AntimicrobChemother 2008; 61:177.

27. Moenster RP, Linneman TW, Finnegan PM, McDonald JR. Daptomycin compared to vancomycinfor the treatment of osteomyelitis: a single-center, retrospective cohort study. Clin Ther 2012;34:1521.

28. Malizos K, Sarma J, Seaton RA, et al. Daptomycin for the treatment of osteomyelitis andorthopaedic device infections: real-world clinical experience from a European registry. Eur J ClinMicrobiol Infect Dis 2016; 35:111.

29. Harting J, Fernandez F, Kelley R, et al. Telavancin for the treatment of methicillin-resistantStaphylococcus aureus bone and joint infections. Diagn Microbiol Infect Dis 2017; 89:294.

30. Lalikian K, Parsiani R, Won R, et al. Ceftaroline for the treatment of osteomyelitis caused bymethicillin-resistant Staphylococcus aureus: a case series. J Chemother 2018; 30:124.

31. Schroeder CP, Van Anglen LJ, Dretler RH, et al. Outpatient treatment of osteomyelitis withtelavancin. Int J Antimicrob Agents 2017; 50:93.

32. Rappo U, Puttagunta S, Shevchenko V, et al. Dalbavancin for the Treatment of Osteomyelitis inAdult Patients: A Randomized Clinical Trial of Efficacy and Safety. Open Forum Infect Dis 2019;6:ofy331.

33. Morata L, Cobo J, Fernández-Sampedro M, et al. Safety and Efficacy of Prolonged Use ofDalbavancin in Bone and Joint Infections. Antimicrob Agents Chemother 2019; 63.

34. Almangour TA, Perry GK, Terriff CM, et al. Dalbavancin for the management of gram-positive



































osteomyelitis: Effectiveness and potential utility. Diagn Microbiol Infect Dis 2019; 93:213.

35. Wunsch S, Krause R, Valentin T, et al. Multicenter clinical experience of real life Dalbavancin use ingram-positive infections. Int J Infect Dis 2019; 81:210.

36. Turner RB, Wilson DE, Saedi-Kwon H, et al. Comparative analysis of neutropenia in patientsreceiving prolonged treatment with ceftaroline. J Antimicrob Chemother 2018; 73:772.

37. Abbott IJ, Jenney AW, Jeremiah CJ, et al. Reduced In Vitro Activity of Ceftaroline by Etest amongClonal Complex 239 Methicillin-Resistant Staphylococcus aureus Clinical Strains from Australia.Antimicrob Agents Chemother 2015; 59:7837.

38. Chuan J, Zhang Y, He X, et al. Systematic Review and Meta-Analysis of the Efficacy and Safety ofTelavancin for Treatment of Infectious Disease: Are We Clearer? Front Pharmacol 2016; 7:330.

39. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA)Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis inAdults. Clin Infect Dis 2015; 61:e26.

40. Euba G, Murillo O, Fernández-Sabé N, et al. Long-term follow-up trial of oral rifampin-cotrimoxazolecombination versus intravenous cloxacillin in treatment of chronic staphylococcal osteomyelitis.Antimicrob Agents Chemother 2009; 53:2672.

41. Nguyen S, Pasquet A, Legout L, et al. Efficacy and tolerance of rifampicin-linezolid compared withrifampicin-cotrimoxazole combinations in prolonged oral therapy for bone and joint infections. ClinMicrobiol Infect 2009; 15:1163.

42. Rao N, Hamilton CW. Efficacy and safety of linezolid for Gram-positive orthopedic infections: aprospective case series. Diagn Microbiol Infect Dis 2007; 59:173.

43. Senneville E, Legout L, Valette M, et al. Effectiveness and tolerability of prolonged linezolidtreatment for chronic osteomyelitis: a retrospective study. Clin Ther 2006; 28:1155.

44. Bassetti M, Vitale F, Melica G, et al. Linezolid in the treatment of Gram-positive prosthetic jointinfections. J Antimicrob Chemother 2005; 55:387.

45. Henry NK, Rouse MS, Whitesell AL, et al. Treatment of methicillin-resistant Staphylococcus aureusexperimental osteomyelitis with ciprofloxacin or vancomycin alone or in combination with rifampin.Am J Med 1987; 82:73.

46. Zimmerli W, Widmer AF, Blatter M, et al. Role of rifampin for treatment of orthopedic implant-relatedstaphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group.JAMA 1998; 279:1537.

47. El Helou OC, Berbari EF, Lahr BD, et al. Efficacy and safety of rifampin containing regimen for



































staphylococcal prosthetic joint infections treated with debridement and retention. Eur J ClinMicrobiol Infect Dis 2010; 29:961.

48. Lora-Tamayo J, Murillo O, Iribarren JA, et al. A large multicenter study of methicillin-susceptible andmethicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implantretention. Clin Infect Dis 2013; 56:182.

49. Perlroth J, Kuo M, Tan J, et al. Adjunctive use of rifampin for the treatment of Staphylococcusaureus infections: a systematic review of the literature. Arch Intern Med 2008; 168:805.

50. Norden CW, Bryant R, Palmer D, et al. Chronic osteomyelitis caused by Staphylococcus aureus:controlled clinical trial of nafcillin therapy and nafcillin-rifampin therapy. South Med J 1986; 79:947.

51. Howden BP, Grayson ML. Dumb and dumber--the potential waste of a useful antistaphylococcalagent: emerging fusidic acid resistance in Staphylococcus aureus. Clin Infect Dis 2006; 42:394.

52. Pushkin R, Iglesias-Ussel MD, Keedy K, et al. A Randomized Study Evaluating Oral Fusidic Acid(CEM-102) in Combination With Oral Rifampin Compared With Standard-of-Care Antibiotics forTreatment of Prosthetic Joint Infections: A Newly Identified Drug-Drug Interaction. Clin Infect Dis2016; 63:1599.

53. Marsot A, Ménard A, Dupouey J, et al. Population pharmacokinetics of rifampicin in adult patientswith osteoarticular infections: interaction with fusidic acid. Br J Clin Pharmacol 2017; 83:1039.

54. Huddleston PM, Steckelberg JM, Hanssen AD, et al. Ciprofloxacin inhibition of experimentalfracture healing. J Bone Joint Surg Am 2000; 82:161.

55. Gentry LO, Rodriguez GG. Oral ciprofloxacin compared with parenteral antibiotics in the treatmentof osteomyelitis. Antimicrob Agents Chemother 1990; 34:40.

56. Laghmouche N, Compain F, Jannot AS, et al. Successful treatment of Pseudomonas aeruginosaosteomyelitis with antibiotic monotherapy of limited duration. J Infect 2017; 75:198.

57. El Helou OC, Berbari EF, Marculescu CE, et al. Outcome of enterococcal prosthetic joint infection:is combination systemic therapy superior to monotherapy? Clin Infect Dis 2008; 47:903.

58. Euba G, Lora-Tamayo J, Murillo O, et al. Pilot study of ampicillin-ceftriaxone combination fortreatment of orthopedic infections due to Enterococcus faecalis. Antimicrob Agents Chemother2009; 53:4305.

59. Hake ME, Young H, Hak DJ, et al. Local antibiotic therapy strategies in orthopaedic trauma:Practical tips and tricks and review of the literature. Injury 2015; 46:1447.

60. Helgeson MD, Potter BK, Tucker CJ, et al. Antibiotic-impregnated calcium sulfate use in combat-related open fractures. Orthopedics 2009; 32:323.



































61. Mader JT, Guckian JC, Glass DL, Reinarz JA. Therapy with hyperbaric oxygen for experimentalosteomyelitis due to Staphylococcus aureus in rabbits. J Infect Dis 1978; 138:312.

62. Goldman RJ. Hyperbaric oxygen therapy for wound healing and limb salvage: a systematic review.PM R 2009; 1:471.


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GRAPHICS

Antibiotic therapy for treatment of osteomyelitis or prosthetic joint infection in adults

Infectious agent Antibiotic regimen Dosing

Empiric therapy Vancomycin PLUS a third- or fourth-generationcephalosporin (such as ceftriaxone,ceftazidime, or cefepime)

As summarized below

Pathogen-specific therapy

Staphylococci,methicillinsusceptible*

Nafcillin 2 g IV every 4 hours

Oxacillin 2 g IV every 4 hours

Cefazolin 2 g IV every 8 hours

Flucloxacillin 2 g IV every 6 hours

Ceftriaxone 2 g IV every 24 hours

Staphylococci,methicillinresistant*

Regimen of choice:

Vancomycin 20 mg/kg loading dose, then 15 mg/kg/dose IVevery 12 hours, not to exceed 2 g per doseinitially

Alternative regimens:

Daptomycin 6 to 10 mg/kg IV once daily

Teicoplanin (where available) 12 mg/kg IV every 12 hours for 3 to 5 doses,followed by 12 mg/kg once daily

Staphylococci,adjunctive agents*

Rifampin 300 to 450 mg orally twice daily

Fusidic acid (where available) 500 mg orally 3 times daily

Gram-negativeorganisms

Ciprofloxacin ** 750 mg orally twice daily or 400 mg IV every12 hours; if treating Pseudomonas, increase IVdose to 400 mg IV every 8 hours

Levofloxacin** 750 mg orally or IV once daily


Ceftazidime** 2 g IV every 8 hours

Cefepime** 2 g IV every 8 to 12 hours

Ertapenem 1 g IV every 24 hours

Meropenem** 1 g IV every 8 hours

Enterococci Monotherapy regimens:

Ampicillin 12 g IV every 24 hours, either continuously orin 6 equally divided doses

Aqueous crystalline penicillin G 20 to 24 million units IV every 24 hours, eithercontinuously or in 6 equally divided doses

Vancomycin 20 mg/kg loading dose, then 15 mg/kg IVevery 12 hours, not to exceed 2 g per dose

Daptomycin 6 to 10 mg/kg IV once daily

Teicoplanin (where available) 12 mg/kg IV every 12 hours for 3 to 5 doses,followed by 12 mg/kg once daily

Combination therapy regimen:

Ampicillin 12 g IV every 24 hours, given eithercontinuously or in 6 equally divided doses

PLUS

Ceftriaxone 2 g IV every 12 to 24 hours

Streptococci,penicillin sensitive

One of the following:

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Aqueous crystalline penicillin G 20 to 24 million units IV every 24 hours, eithercontinuously or in 6 equally divided doses

Ampicillin 12 g IV every 24 hours, either continuously orin 6 equally divided doses


Vancomycin 20 mg/kg loading dose, then 15 mg/kg/dose IVevery 12 hours, not to exceed 2 g per dose,initially

Cutibacterium(formerlyPropionibacterium)acnes


Aqueous crystalline penicillin G 20 million units IV every 24 hours, eithercontinuously or in 6 divided doses


In stable patients, antibiotics may be held pending establishment of microbiologic diagnosis or obtaining cultures frombone debridement or biopsy. The total duration of antibiotic therapy depends on individual patient circumstances(refer to the UpToDate content on treatment of osteomyelitis and prosthetic joint infection for further discussion). Thedoses in this table are intended for adults with normal renal function. The doses of many of these agents must beadjusted in the setting of renal insufficiency; refer to the Lexicomp drug-specific monographs for renal doseadjustments.

IV: intravenously; PJI: prosthetic joint infection.* For patients with Staphylococcus aureus PJI and residual hardware following surgery, we favor use of adjunctive rifampin. Tomitigate the emergence of resistance, rifampin should not be started until the patient has received several days of anti-staphylococcal therapy. We favor administration of rifampin 450 orally twice daily; the dose may be reduced to 300 mg orallytwice daily in the setting of nausea. There should be careful screening drug-drug interactions prior to initiation of rifampin.¶ Use of ceftriaxone for treatment of staphylococcal osteomyelitis is not universally accepted. In our practice, we use it as analternative regimen for isolates with oxacillin minimum inhibitory concentration <0.5 mcg/mL in the absence of concomitantbacteremia; once-daily dosing is a convenient outpatient regimen.Δ In adults, vancomycin is dosed based on actual body weight. Target troughs for vancomycin should be chosen with theguidance of a local infectious disease physician based on the pathogen, in vitro susceptibility, and the use of rifampin or localvancomycin therapy, with a target trough concentration of at least 10 mcg/mL. It is unknown if a higher vancomycin troughlevel of 15 to 20 mcg/mL is routinely needed. Refer to the UpToDate topic review on vancomycin parenteral dosing and serumconcentration monitoring in adults.◊ Ceftaroline has been used successfully for treatment of osteomyelitis but has been associated with increased risk ofneutropenia. Pending further study, use of ceftaroline should be reserved for patients unable to receive other therapies.Ceftaroline susceptibility must be confirmed; the prevalence of resistance is high in some regions. Daptomycin may be used forvancomycin-resistant enterococci; confirm susceptibility.§ Standard daptomycin dosing (as approved by the US Food and Drug Administration) for treatment of bacteremia orosteomyelitis is 6 mg/kg IV once daily. Because daptomycin exhibits concentration-dependent killing, some experts recommenddoses of up to 8 to 10 mg/kg IV once daily, which appear safe; further study is needed.¥ Not available in the United States. Fusidic acid should not be used alone; it must be combined with a second active agent toreduce the likelihood of selection for drug resistance. When rifampin is combined with fusidic acid, fusidic levels may be reduced.‡ The teicoplanin dose should be adjusted to attain a trough concentration of >20 mcg/mL.† Oral ciprofloxacin at dose shown in table achieves therapeutic levels for treatment of Pseudomonas aeruginosa.** Ciprofloxacin, levofloxacin, ceftazidime, cefepime, and meropenem have activity against P. aeruginosa; confirm susceptibility.¶¶ The possibility of prolonged QTc interval, tendinopathy, neuropathy, or development of an aneurysm should be reviewed andmonitored when using fluoroquinolones. For more information, please refer to the UpToDate topic on fluoroquinolones.ΔΔ Ceftriaxone and ertapenem have no activity against P. aeruginosa, but are appropriate for other gram-negative organisms, ifsusceptible.◊◊ For treatment of infection due to penicillin-susceptible enterococci, it is unclear whether combination therapy is superior tomonotherapy, particularly if thorough debridement is performed. In the setting of retained hardware, we favor combinationtherapy for PJI due to Enterococcus faecalis with ampicillin and ceftriaxone. We do not use this approach for treatment of PJIdue to non-faecalis species of penicillin-susceptible enterococci because synergy with these agents in vitro is variable and clinicaldata are not available in patients with PJI due to non-faecalis species [11]. If antibiotic-impregnated material containinggentamicin is implanted at the time of debridement, then monotherapy is likely sufficient and we favor treatment with eitherintravenous ampicillin or penicillin (vancomycin or daptomycin are acceptable alternative agents for patients with proven beta-lactam hypersensitivity). For treatment of infection due to penicillin-resistant enterococci, the preferred agent is vancomycin;daptomycin or teicoplanin (where available) are acceptable alternative agents.§§ For patients with Cutibacterium spp infection and beta-lactam hypersensitivity, reasonable alternative agents includevancomycin, a tetracycline (doxycycline or minocycline), or moxifloxacin.

Data from:1. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice

Δ

§§



guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013; 56:e1.2. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for

the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015; 61:e26.3. Figueroa DA, Mangini E, Amodio-Groton M, et al. Safety of high-dose intravenous daptomycin treatment: three-year

cumulative experience in a clinical program. Clin Infect Dis 2009; 49:177.4. Benvenuto M, Benziger DP, Yankelev S, Vigliani G. Pharmacokinetics and tolerability of daptomycin at doses up to 12

milligrams per kilogram of body weight once daily in healthy volunteers. Antimicrob Ther Chemother 2006; 50:3245.5. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the

treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:285.6. Teicoplanin. The UK electronic Medicines Compendium (eMC) summary of product characteristics. Last updated February

01, 2018. UK electronic Medicines Compendium. (Available online at https://www.medicines.org.uk/emc/ (AccessedJanuary 28, 2019)).

7. Sodium fusidate. The UK electronic Medicines Compendium (eMC) summary of product characteristics. Last updatedAugust 30, 2018. UK electronic Medicines Compendium. (Available online at https://www.medicines.org.uk/emc/(Accessed January 28, 2019)).

8. Euba G, Lora-Tamayo J, Murillo O, et al. Pilot study of ampicillin-ceftriaxone combination for treatment of orthopedicinfections due to Enterococcus faecalis. Antimicrob Agents Chemother 2009; 53:4305.

9. Calhoun JH, Manring MM. Adult osteomyelitis. Infect Dis Clin North Am 2005; 19:765.10. Pushkin R, Iglesias-Ussel MD, Keedy K, et al. A randomized study evaluating oral fusidic acid (CEM-102) in combination

with oral rifampin compared with standard-of-care antibiotics for treatment of prosthetic joint infections: A newlyidentified drug-drug interaction. Clin Infect Dis 2016; 63:1599.

11. Lorenzo MP, Kidd JM, Jenkins SG, et al. In vitro activity of ampicillin and ceftriaxone against ampicillin-susceptibleEnterococcus faecium. J Antimicrob Chemother 2019; 74:2269.


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Suppression of osteomyelitis or prosthetic joint infection in adults: Oral antibioticregimens*


Staphylococci,methicillinsusceptible


Cefadroxil 500 to 1000 mg twice daily

Cephalexin 500 mg 3 or 4 times daily, or 1000 mg 2 or 3times daily

Dicloxacillin 500 mg 3 or 4 times daily

Flucloxacillin 500 mg 3 or 4 times daily

Staphylococci,methicillinresistant


Trimethoprim-sulfamethoxazole 1 double-strength tablet twice daily

Doxycycline 100 mg twice daily

Minocycline 100 mg twice daily

Clindamycin 600 mg 3 times daily

Gram-negativeorganisms



Ciprofloxacin 500 mg twice daily

Levofloxacin 500 mg once daily

Penicillin-sensitivestreptococci andenterococci


Amoxicillin 500 mg 2 to 3 times daily

Penicillin V K 500 mg 2 to 3 times daily

Cutibacterium(formerlyPropionibacterium)acnes


Amoxicillin 500 mg 2 to 3 times daily

Penicillin V K 500 mg 2 to 3 times daily

The doses recommended above are intended for adults with normal renal function; the doses of some of these agentsmust be adjusted in patients with renal insufficiency. Refer to the Lexicomp drug-specific monographs for renal doseadjustments.

PJI: Prosthetic joint infection.* Initial treatment of PJI consists of definitive antibiotic therapy (refer to the separate UpToDate table); suppressive therapy iswarranted only for individuals with retained hardware and/or necrotic bone not amenable to complete debridement. The optimalduration of oral suppressive antibiotic therapy is uncertain. Refer to the UpToDate topic on the treatment of PJI for furtherdiscussion.¶ The choice of antibiotic regimen should be based on susceptibility, as well as patient drug allergies, intolerances, and potentialdrug-drug interactions or contraindications to a specific agent.Δ The agents listed for methicillin-resistant staphylococci may be used for suppression of methicillin-susceptible staphylococci inpatients with beta-lactam allergy or intolerance, provided the organism is susceptible.◊ Ciprofloxacin and levofloxacin have activity against Pseudomonas aeruginosa.

Data from:1. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice

guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013; 56:e1.2. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for

the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015; 61:e26.



Douglas R Osmon, MD Nothing to disclose Aaron J Tande, MD Nothing to disclose Denis Spelman, MBBS,FRACP, FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by

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Douglas R Osmon, MD Nothing to disclose Aaron J Tande, MD Nothing to disclose Denis Spelman, MBBS,FRACP, FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose




Osteomyelitis associated with open fractures in adults - UpToDate

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Osteomyelitis associated with open fractures in adultsAuthor: Steven K Schmitt, MD, FIDSA Section Editor: Denis Spelman, MBBS, FRACP, FRCPA, MPH Deputy Editor: Elinor LBaron, MD, DTMH


Literature review current through: Feb 2020. | This topic last updated: Nov 25, 2019.

INTRODUCTION

Osteomyelitis may develop as a result of contamination of open fractures [1-3].

The epidemiology, microbiology, clinical manifestations, treatment, and prevention of osteomyelitis in thesetting of open fractures will be reviewed here.

General principles of fracture management are discussed separately. (See "General principles of fracturemanagement: Early and late complications", section on 'Open fractures' and "General principles offracture management: Early and late complications", section on 'Osteomyelitis'.)

General issues related to osteomyelitis are discussed separately. (See "Osteomyelitis in adults: Clinicalmanifestations and diagnosis" and "Osteomyelitis in adults: Treatment".)

Issues related to prosthetic joint infections are discussed separately. (See "Prosthetic joint infection:Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Prosthetic joint infection:Treatment".)

Issues related to infection following nail puncture are discussed separately. (See "Pseudomonasaeruginosa skin and soft tissue infections", section on 'Infection following nail puncture'.)

Issues related to injury associated with bites are discussed separately. (See "Animal bites (dogs, cats,and other animals): Evaluation and management" and "Human bites: Evaluation and management".)

Issues related to injury associated with water are discussed separately. (See "Soft tissue infectionsfollowing water exposure".)

EPIDEMIOLOGY

Osteomyelitis can occur in up to 25 percent of open fractures; the risk depends upon the following factors

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[4-10]:

In one review including more than 1100 open fracture wounds, the risk of infection with open tibia fracturewas twice as high as for open fracture of other sites (10.5 versus 5.3 percent) [7]. The infection rate afteropen hand fracture is relatively low; in one review including twelve articles (4 prospective, 8retrospective) and 1669 open fractures of the hand, the infection rate was approximately 3 to 4 percent[11].

MICROBIOLOGY

Microorganisms can be introduced directly into bone in the setting of fracture or via contiguous spreadfrom injury to overlying soft tissue. They proliferate in the presence of devitalized tissues containingclotted blood and necrotic bone.

Pathogens may include skin flora, environmental organisms, or nosocomial pathogens. The mostcommon organisms include Staphylococcus aureus, coagulase-negative staphylococci, and aerobicgram-negative bacilli. Other less commonly implicated pathogens include enterococci, anaerobes, fungi,and mycobacteria [6,12-18]. If the fracture is associated with water, infection may be caused byPseudomonas, Aeromonas, or Vibrio species. (See "Soft tissue infections following water exposure".)

The microbiologic diagnosis is established via cultures obtained at the time of debridement for possibleinfection, rather than at the time of initial debridement following fracture. Cultures obtained at the time ofinitial debridement correlate with established pathogens of osteomyelitis in only 25 percent of cases[19,20]. Not all microbes colonizing the wound at the time of injury cause sustained infection in the bone,and pathogens not present at the initial injury may colonize and infect wounds subsequently.

CLINICAL MANIFESTATIONS

The approach to classification of open fractures is summarized in the table (table 1).

Acute osteomyelitis following fracture usually presents with gradual progression of dull localized painover several days. Local findings (tenderness, warmth, erythema, swelling) and systemic symptoms(fever, rigors) may be present. Decreased range of motion, point tenderness, and joint effusions may beseen but are also present with uninfected fractures, making clinical diagnosis potentially difficult.

In some cases, osteomyelitis presents with few symptoms or signs. This is more common with subacuteor chronic infections, with infections of the hip, pelvis, or vertebrae, and in young patients.

Severity of injury, including whether concurrent vascular and/or neurologic damage is present●

Degree of bacterial contamination●

Adequacy of surgical debridement●

Administration of antibiotics (including the timing as well as the type)●


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Chronic osteomyelitis may present with pain, erythema, or swelling, sometimes in association with adraining sinus tract. Fractures that are healing slower than expected or that remain extremely painfuldespite adequate immobilization may be a sign that osteomyelitis is present.

After open fracture, non-union is the most common consequence and manifestation of osteomyelitis.Non-unions commonly present with persistent pain, swelling, or instability beyond the time when healingshould normally have occurred.

Additional manifestations of osteomyelitis and non-union associated with fracture are discussedseparately. (See "General principles of fracture management: Early and late complications", section on'Osteomyelitis'.)

DIAGNOSIS

The approach to diagnosis of osteomyelitis following open fracture is the same as the approach todiagnosis of osteomyelitis due to other causes; this is discussed separately. (See "Osteomyelitis inadults: Clinical manifestations and diagnosis" and "Approach to imaging modalities in the setting ofsuspected nonvertebral osteomyelitis".)

TREATMENT

Following a fracture, initial management of osteomyelitis or infected non-union consists of surgicaldebridement with irrigation, obtaining bone biopsy for culture, fracture fixation (if needed), andantimicrobial therapy tailored to culture and susceptibility data [15,21-31].

In type III wounds, closure of soft tissue may require flaps or grafts of skin or tissue [32].

To achieve optimal union in the setting of concomitant osteomyelitis, it may be necessary to administerparenteral antibiotic therapy for as long as fixation hardware remains in place. Once fracture union isachieved, fixation hardware should be removed (if possible), with additional debridement.

The approach to antibiotic therapy for patients with retained hardware is discussed separately. (See"Osteomyelitis in adults: Treatment", section on 'Retained hardware'.)

The approach to antibiotic therapy for patients with no retained hardware is discussed separately. (See"Osteomyelitis in adults: Treatment", section on 'No retained hardware'.)

Antibiotic selection and other issues related to treatment of osteomyelitis are discussed in detailseparately. (See "Osteomyelitis in adults: Treatment", section on 'Antibiotic therapy'.)

PREVENTION







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Measures for prevention of osteomyelitis following open fracture include prompt debridement, surgicalfixation (if needed), and antibiotic therapy [1].

Initial fracture management — General principles of acute fracture management are discussedseparately. (See "General principles of acute fracture management" and "General principles of fracturemanagement: Early and late complications", section on 'Open fractures'.)

In general, initial fracture management consists of thorough irrigation and debridement. Some havesuggested that open fractures should be debrided within six hours of injury. No definitive association hasbeen made between delayed debridement and higher infection rates; further study is needed [33-35].

The decision regarding use of fixation hardware for stabilization is made on a case-by-case basis.

At the time of initial debridement, there is no need for operative routine cultures. If subsequentdebridement is performed for suspected infection, collection of operative cultures is warranted at thattime. (See 'Microbiology' above.)

Once union is achieved, fixation hardware may be removed and additional debridement performed ifneeded. Final steps include bone grafting (if needed) and wound closure [22-31,36].

Primary closure may be reasonable for debrided wounds with no contamination, good residual softtissue, and good vascular supply [37]. Delayed wound closure is generally warranted in Gustilo type II orIII fractures (table 1).

Antibiotics after open fracture — The use of antimicrobial agents for dirty procedures or establishedinfection is classified as treatment of presumed infection, rather than prophylaxis. (See "Antimicrobialprophylaxis for prevention of surgical site infection in adults", section on 'Wound classification'.)

Following open fracture, prompt administration of antibiotics (ideally within six hours) is warranted toreduce the risk of osteomyelitis [2,3,38-40]. This approach is supported by a meta-analysis including 913patients with open fractures [36]; use of antibiotics was associated with an absolute reduction in infectionof 0.08 (95% CI 0.04-0.12) [36].

Antibiotic selection — Antibiotic regimens for patients with open fractures are summarized in thetable (table 2).

For patients with type I and type II fractures (table 1), antibiotic therapy should include activity againstgram-positive organisms. Cefazolin is a reasonable regimen; for patients at risk for methicillin-resistant S.aureus (table 3), gram-positive coverage should consist of vancomycin. Dosing is summarized in thetable (table 2).

For patients with type III fractures (table 1), antibiotic therapy should include activity against gram-negative organisms (in addition to gram-positive coverage outlined above) [2,41]. We are in agreementwith the EAST Guidelines which recommend gentamicin; ceftriaxone (monotherapy) is an acceptablealternative [2,42]. Dosing is summarized in the table (table 2).


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For patients with open fracture associated with soil contamination, we favor addition of metronidazole tothe above regimens, for coverage of Clostridium spp.

For patients with open fracture associated with freshwater contamination, we favor piperacillin-tazobactam for activity against gram-negative pathogens such as Pseudomonas and Aeromonasspecies.

For patients with open fracture associated with seawater contamination, we favor piperacillin-tazobactam(as for freshwater) as well as doxycycline for activity against Vibrio species. Dosing is summarized in thetable (table 2).

Data to guide the above approach to antibiotic selection are limited, and the optimal approach isuncertain. Our approach is guided by the typical microbiology of such infections as well as general trendsin antimicrobial resistance.

Duration — The duration of antibiotic therapy depends on the classification of the fracture (table 1)[2,3,43,44]:

Prolonged administration of antibiotics does not reduce the risk of infection and can lead to thedevelopment of resistant organisms [3,45].

Tetanus prophylaxis — Open fractures are tetanus-prone wounds [46,47]. The patient's tetanusimmunization status should be determined; tetanus toxoid, diphtheria-tetanus-acellular pertussis, boostertetanus toxoid-reduced diphtheria toxoid-acellular pertussis, or tetanus-diphtheria toxoids adsorbedshould be administered as indicated (table 4). The need for tetanus immune globulin should also beassessed (table 4). (See "Tetanus".)



SUMMARY

For Gustilo type I and II open fractures, antibiotics may be discontinued 24 hours after woundclosure.

●

For Gustilo type III open fractures, antibiotics may be discontinued after 72 hours or within a dayafter soft tissue injuries have been closed.

●

Osteomyelitis may develop as a result of contamination of open fractures in up to 25 percent of●

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REFERENCES


2. Hoff WS, Bonadies JA, Cachecho R, Dorlac WC. East Practice Management Guidelines WorkGroup: update to practice management guidelines for prophylactic antibiotic use in open fractures.J Trauma 2011; 70:751.

3. Pasquale M, Fabian TC. Practice management guidelines for trauma from the Eastern Associationfor the Surgery of Trauma. J Trauma 1998; 44:941.

4. Merritt K. Factors increasing the risk of infection in patients with open fractures. J Trauma 1988;

cases. Microorganisms can be introduced directly into bone in the setting of open fractures or viacontiguous spread from injury to overlying soft tissue. Pathogens may include skin flora,environmental organisms, or nosocomial pathogens. (See 'Epidemiology' above and 'Microbiology'above.)

The approach to classification of open fractures is summarized in the table (table 1). The approachto diagnosis of osteomyelitis following open fracture is the same as the approach to diagnosis ofosteomyelitis due to other causes; this is discussed separately. (See 'Clinical manifestations' aboveand "Osteomyelitis in adults: Clinical manifestations and diagnosis".)

●

Following a fracture, initial management of osteomyelitis or infected non-union consists of surgicaldebridement with irrigation, obtaining bone biopsy for culture, fracture fixation (if needed), andantimicrobial therapy tailored to culture and susceptibility data. To achieve optimal union, it may benecessary to administer parenteral antibiotic therapy for as long as fixation hardware remains inplace. Once fracture union is achieved, fixation hardware should be removed (if possible), withadditional debridement if needed. (See 'Treatment' above.)

●

Measures for prevention of osteomyelitis following open fracture include prompt debridement,surgical fixation (if needed), antibiotic therapy, and assessment regarding need for tetanusprophylaxis. (See 'Prevention' above.)

●

Following open fracture, prompt administration of antibiotics (ideally within six hours) is warranted toreduce the risk of osteomyelitis (table 2). For patients with type I and type II fractures, antibiotictherapy should include activity against gram-positive organisms. For patients with type III fractures,antibiotic therapy should include activity against gram-positive and gram-negative organisms. Theduration of antibiotic therapy depends on the classification of the fracture. (See 'Antibiotics after openfracture' above.)

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28:823.

5. DeLong WG Jr, Born CT, Wei SY, et al. Aggressive treatment of 119 open fracture wounds. JTrauma 1999; 46:1049.


7. Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds. Clin Orthop RelatRes 1989; :36.

8. Tsukayama DT. Pathophysiology of posttraumatic osteomyelitis. Clin Orthop Relat Res 1999; :22.

9. Lavery LA, Walker SC, Harkless LB, Felder-Johnson K. Infected puncture wounds in diabetic andnondiabetic adults. Diabetes Care 1995; 18:1588.

10. Court-Brown CM, Rimmer S, Prakash U, McQueen MM. The epidemiology of open long bonefractures. Injury 1998; 29:529.

11. Ketonis C, Dwyer J, Ilyas AM. Timing of Debridement and Infection Rates in Open Fractures of theHand: A Systematic Review. Hand (N Y) 2017; 12:119.


13. Khatod M, Botte MJ, Hoyt DB, et al. Outcomes in open tibia fractures: relationship between delay intreatment and infection. J Trauma 2003; 55:949.


15. Trampuz A, Zimmerli W. Diagnosis and treatment of infections associated with fracture-fixationdevices. Injury 2006; 37 Suppl 2:S59.

16. Haas DW, McAndrew MP. Bacterial osteomyelitis in adults: evolving considerations in diagnosisand treatment. Am J Med 1996; 101:550.

17. Karam GH, Ackley AM, Dismukes WE. Posttraumatic Aeromonas hydrophila osteomyelitis. ArchIntern Med 1983; 143:2073.

18. Lavery LA, Harkless LB, Felder-Johnson K, Mundine S. Bacterial pathogens in infected puncturewounds in adults with diabetes. J Foot Ankle Surg 1994; 33:91.

19. Kindsfater K, Jonassen EA. Osteomyelitis in grade II and III open tibia fractures with latedebridement. J Orthop Trauma 1995; 9:121.

20. Lee J. Efficacy of cultures in the management of open fractures. Clin Orthop Relat Res 1997; :71.

































21. Roesgen M, Hierholzer G, Hax PM. Post-traumatic osteomyelitis. Pathophysiology andmanagement. Arch Orthop Trauma Surg 1989; 108:1.

22. Cierny G, Mader JT. Adult chronic osteomyelitis. Orthopedics 1984; 7:1557.

23. Böhm E, Josten C. What's new in exogenous osteomyelitis? Pathol Res Pract 1992; 188:254.

24. Meadows SE, Zuckerman JD, Koval KJ. Posttraumatic tibial osteomyelitis: diagnosis, classification,and treatment. Bull Hosp Jt Dis 1993; 52:11.

25. Anthony JP, Mathes SJ, Alpert BS. The muscle flap in the treatment of chronic lower extremityosteomyelitis: results in patients over 5 years after treatment. Plast Reconstr Surg 1991; 88:311.

26. May JW Jr, Jupiter JB, Gallico GG 3rd, et al. Treatment of chronic traumatic bone wounds.Microvascular free tissue transfer: a 13-year experience in 96 patients. Ann Surg 1991; 214:241.

27. Culliford AT 4th, Spector J, Blank A, et al. The fate of lower extremities with failed free flaps: asingle institution's experience over 25 years. Ann Plast Surg 2007; 59:18.

28. Clifford RP, Beauchamp CG, Kellam JF, et al. Plate fixation of open fractures of the tibia. J BoneJoint Surg Br 1988; 70:644.

29. Clifford RP, Lyons TJ, Webb JK. Complications of external fixation of open fractures of the tibia.Injury 1987; 18:174.

30. Chapman MW. The role of intramedullary fixation in open fractures. Clin Orthop Relat Res 1986;:26.

31. Etter C, Burri C, Claes L, et al. Treatment by external fixation of open fractures associated withsevere soft tissue damage of the leg. Biomechanical principles and clinical experience. Clin OrthopRelat Res 1983; :80.

32. Mehta D, Abdou S, Stranix JT, et al. Comparing Radiographic Progression of Bone Healing inGustilo IIIB Open Tibia Fractures Treated With Muscle Versus Fasciocutaneous Flaps. J OrthopTrauma 2018; 32:381.

33. Prodromidis AD, Charalambous CP. The 6-Hour Rule for Surgical Debridement of Open TibialFractures: A Systematic Review and Meta-Analysis of Infection and Nonunion Rates. J OrthopTrauma 2016; 30:397.

34. Schenker ML, Yannascoli S, Baldwin KD, et al. Does timing to operative debridement affectinfectious complications in open long-bone fractures? A systematic review. J Bone Joint Surg Am2012; 94:1057.

35. Calhoun JH. Optimal timing of operative debridement: a known unknown: commentary on an article


































by Mara L. Schenker, MD, et al.: “Does timing to operative debridement affect infectiouscomplications in open long-bone fractures? A systematic review”. J Bone Joint Surg Am 2012;94:e90.

36. Gosselin RA, Roberts I, Gillespie WJ. Antibiotics for preventing infection in open limb fractures.Cochrane Database Syst Rev 2004; :CD003764.

37. Rajasekaran S. Early versus delayed closure of open fractures. Injury 2007; 38:890.

38. Patzakis MJ, Wilkins J, Moore TM. Considerations in reducing the infection rate in open tibialfractures. Clin Orthop Relat Res 1983; :36.

39. Seligson D, Henry SL. Treatment of compound fractures. Am J Surg 1991; 161:693.

40. Patzakis MJ, Bains RS, Lee J, et al. Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds. JOrthop Trauma 2000; 14:529.

41. Vasenius J, Tulikoura I, Vainionpää S, Rokkanen P. Clindamycin versus cloxacillin in the treatmentof 240 open fractures. A randomized prospective study. Ann Chir Gynaecol 1998; 87:224.

42. Rodriguez L, Jung HS, Goulet JA, et al. Evidence-based protocol for prophylactic antibiotics in openfractures: improved antibiotic stewardship with no increase in infection rates. J Trauma Acute CareSurg 2014; 77:400.

43. Hauser CJ, Adams CA Jr, Eachempati SR, Council of the Surgical Infection Society. SurgicalInfection Society guideline: prophylactic antibiotic use in open fractures: an evidence-basedguideline. Surg Infect (Larchmt) 2006; 7:379.

44. Gillespie WJ, Walenkamp GH. Antibiotic prophylaxis for surgery for proximal femoral and otherclosed long bone fractures. Cochrane Database Syst Rev 2010; :CD000244.

45. Dellinger EP, Caplan ES, Weaver LD, et al. Duration of preventive antibiotic administration for openextremity fractures. Arch Surg 1988; 123:333.

46. Talan DA, Citron DM, Abrahamian FM, et al. Bacteriologic analysis of infected dog and cat bites.Emergency Medicine Animal Bite Infection Study Group. N Engl J Med 1999; 340:85.

47. Muguti GI, Dixon MS. Tetanus following human bite. Br J Plast Surg 1992; 45:614.































GRAPHICS

Gustilo-Anderson open fracture grading

Type Wound size Contamination Fracture

Vascularinjury

requiringrepair

Soft tissuecoverage

I Wound <1 cm Minimal Minimalcomminution;no periostealstripping

No Adequate

II Wound >1 cm Moderate Moderatecomminution;minimal periostealstripping

No Adequate

IIIA Any size Severe Severecomminution orsegmentalfractures;periostealstripping

No Adequate; maybecomeinadequate withdebridements

IIIB Any size Severe Severecomminution orsegmentalfractures;periostealstripping

No Inadequate(rotation flap orfree flap)

IIIC Any size Severe Severecomminution orsegmentalfractures;periostealstripping

Yes Inadequate(rotation flap orfree flap)

References:1. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long

bones: retrospective and prospective analyses. J Bone Joint Surg Am 1976; 58:453.2. Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures relative to treatment and results.

Orthopedics 1987; 10:1781.


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◊



Preventive antibiotic regimens for patients with open fractures

Absence of potential

soil or watercontamination

Presence of potentialsoil contamination

(in absence of watercontamination)

Presence of watercontamination

Gustilo-Anderson fracture type I or II*

Preferred regimen Cefazolin 2 g IV every 8hours

Cefazolin 2 g IV every 8hours

OR

Ceftriaxone 2 g IV every24 hours

PLUS

Metronidazole 500 mg IVevery 8 hours

No modification neededfor fracture type I or II

Alternative regimen forpatients with beta-lactamhypersensitivity

Vancomycin 20 mg/kgloading dose, then 15mg/kg/dose IV every 12hours

Clindamycin 900 mg IVevery 8 hours

No modification neededfor fracture type I or II

Gustilo-Anderson fracture type III

Preferred regimen Ceftriaxone 2 g IV every24 hours

OR


PLUS

Gentamicin 5 mg/kg IVevery 24 hours

Ceftriaxone 2 g IV every24 hours

OR


PLUS


PLUS

Metronidazole 500 mg IVevery 8 hours

Fresh watercontamination:

Piperacillin-tazobactam4.5 g IV every 6hours

Sea water contamination:Piperacillin-tazobactam(as above)

PLUS

Doxycycline 100 mg IVor orally every 12hours

Alternative regimen forpatients with beta-lactamhypersensitivity



PLUS


Fresh watercontamination:

Imipenem 500 mg IVevery 6 hours

OR

Meropenem 1 g IVevery 8 hours

Sea water contamination:Imipenem ormeropenem (asabove)

PLUS

Doxycycline 100 mg IVor orally every 12hours

IV: intravenous.* For type I and II open fractures, prophylactic antibiotics may be discontinued 24 hours after wound closure.¶ For patients >120 kg, cefazolin dosing consists of 3 g IV every 8 hours.Δ For patients at risk for methicillin-resistant Staphylococcus aureus (MRSA), gram-positive coverage should consist ofvancomycin in place of cefazolin.◊ For patients at risk for MRSA, vancomycin should be added to the regimen.

¶Δ ¶Δ

◊

§

◊

¶Δ

◊

¶Δ ◊¥

◊¥

‡

◊

◊

◊

‡



§ For Gustilo type III open fractures, prophylactic antibiotics may be discontinued after 72 hours or within a day after soft tissueinjuries have been closed.¥ For patients on vancomycin, imipenem or meropenem may be used in place of piperacillin-tazobactam, to minimize thelikelihood of nephrotoxicity associated with coadministration of vancomycin and piperacillin-tazobactam.‡ A fluoroquinolone (levofloxacin or ciprofloxacin) may be used as an alternative to doxycycline.


¶

Δ Δ ◊

§ §

¥



Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection

Health care-associated risk factors include:

Recent hospitalization

Residence in a long-term care facility

Recent surgery

Hemodialysis

Additional risk factors for MRSA infection include:

HIV infection

Injection drug use

Prior antibiotic use

Factors associated with MRSA outbreaks include:

Incarceration

Military service

Sharing sports equipment

Sharing needles, razors, or other sharp objects


¶

Δ Δ ◊

§ §

¥



Wound management and tetanus prophylaxis

Previous dosesof tetanus

toxoid*

Clean and minor wound All other wounds

Tetanus toxoid-containing vaccine

Human tetanusimmune globulin

Tetanus toxoid-containing vaccine

Human tetanusimmune globulin

<3 doses or unknown Yes No Yes Yes

≥3 doses Only if last dose given≥10 years ago

No Only if last dose given≥5 years ago

No

Appropriate tetanus prophylaxis should be administered as soon as possible following a wound but should be giveneven to patients who present late for medical attention. This is because the incubation period is quite variable; mostcases occur within 8 days, but the incubation period can be as short as 3 days or as long as 21 days. For patients whohave been vaccinated against tetanus previously but who are not up to date, there is likely to be little benefit inadministering human tetanus immune globulin more than 1 week or so after the injury. However, for patients thoughtto be completely unvaccinated, human tetanus immune globulin should be given up to 21 days following the injury;Td or Tdap should be given concurrently to such patients.

DT: diphtheria-tetanus toxoids adsorbed; DTP/DTwP: diphtheria-tetanus whole-cell pertussis; DTaP: diphtheria-tetanus-acellularpertussis; Td: tetanus-diphtheria toxoids absorbed; Tdap: booster tetanus toxoid-reduced diphtheria toxoid-acellular pertussis;TT: tetanus toxoid.* Tetanus toxoid may have been administered as DT, DTP/DTwP (no longer available in the United States), DTaP, Td, Tdap, orTT (no longer available in the United States).¶ Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; or woundsresulting from missiles, crushing, burns, or frostbite.Δ The preferred vaccine preparation depends upon the age and vaccination history of the patient:

<7 years: DTaP.Underimmunized children ≥7 and <11 years who have not received Tdap previously: Tdap. Children who receive Tdap atage 7 through 9 years should receive another dose of Tdap at age 11 through 12 years.≥11 years: A single dose of Tdap is preferred to Td for all individuals in this age group who have not previously receivedTdap; otherwise, Td or Tdap can be administered without preference. Pregnant women should receive Tdap during eachpregnancy.

◊ 250 units intramuscularly at a different site than tetanus toxoid; intravenous immune globulin should be administered ifhuman tetanus immune globulin is not available. Persons with HIV infection or severe immunodeficiency who have contaminatedwounds should also receive human tetanus immune globulin, regardless of their history of tetanus immunization.§ The vaccine series should be continued through completion as necessary.¥ Booster doses given more frequently than every 5 years are not needed and can increase adverse effects.

References:

1. Liang JL, Tiwari T, Moro P, et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States:Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2018; 67:1.

2. Havers FP, Moro PL, Hunter P, et al. Use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines:Updated recommendations of the Advisory Committee on Immunization Practices - United States, 2019. MMWR MorbMortal Wkly Rep 2020; 69:77.



Steven K Schmitt, MD, FIDSA Nothing to disclose Denis Spelman, MBBS, FRACP, FRCPA, MPH Nothing todisclose Elinor L Baron, MD, DTMH Nothing to disclose



¶

Δ Δ ◊

§ §

¥





Steven K Schmitt, MD, FIDSA Nothing to disclose Denis Spelman, MBBS, FRACP, FRCPA, MPH Nothing todisclose Elinor L Baron, MD, DTMH Nothing to disclose




Pelvic osteomyelitis and other infections of the bony pelvis in adults - UpToDate

https://www.uptodate.com/...t?search=osteomyelitis&source=search_result&selectedTitle=10~150&usage_type=default&display_rank=10[19.03.2020 15:31:17]


Pelvic osteomyelitis and other infections of the bony pelvis inadultsAuthor: Daniel J Sexton, MD Section Editor: Denis Spelman, MBBS, FRACP, FRCPA, MPH Deputy Editor: Elinor L Baron,MD, DTMH


Literature review current through: Feb 2020. | This topic last updated: Dec 17, 2019.

INTRODUCTION

Infections of the bones and joints of the pelvis may arise hematogenously, secondary to trauma orsurgery via direct inoculation of pathogens into bone, or via contiguous spread of infection from softtissues within or outside the bony walls of the pelvis. These infections may manifest as pelvicosteomyelitis or septic arthritis with contiguous spread to the adjacent bony margins.

Issues related to pelvic osteomyelitis and septic arthritis of the two principle joints of the pelvis (the pubicsymphysis and sacroiliac joint) will be reviewed here.

General issues related to the pathogenesis and classification of osteomyelitis and the clinical features ofother types of osteomyelitis are discussed separately. (See "Osteomyelitis in adults: Clinicalmanifestations and diagnosis" and "Pathogenesis of osteomyelitis" and "Osteomyelitis associated withopen fractures in adults".)

Nonsuppurative processes involving the sacroiliac joint are discussed separately. (See "Clinicalmanifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axialspondyloarthritis) in adults" and "Clinical manifestations and diagnosis of arthritis associated withinflammatory bowel disease and other gastrointestinal diseases".)

Clinical manifestations of osteomyelitis and septic arthritis are discussed separately. (See "Osteomyelitisin adults: Clinical manifestations and diagnosis" and "Septic arthritis in adults".)

EPIDEMIOLOGY

Among the bones within the pelvis, ischium is the bone most commonly associated with osteomyelitis.

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Predisposing factors for pelvic osteomyelitis and pelvic septic arthritis include [1-6]:

These risk factors may predispose to infection at one or several bony sites in the pelvis. As an example,pressure ulcers predominantly predispose to infections of the sacrum and adjacent portions of the ilium.Injection drug use, cardiac catheterization, and bacteremia have a propensity to cause infections of thepubis. Pelvic or urologic surgery can result in infection of the pubis as well as other sites such as thesacroiliac joint.

Rarely, infection arises spontaneously without an identifiable cause; such cases are likely complicationsof bacteremia that developed from an unrecognized site or event [8]. In some circumstances, it may beimpossible to determine if trauma alone or trauma plus an incidental bacteremia led to the subsequentinfection.

ANATOMY

The pelvic walls contain bone, ligaments, and muscles (figure 1). The bony pelvis consists of two hipbones (os coxae) that are joined in front by the pubic symphysis. The os coxae articulate posteriorly withthe sacrum. The hip (coxal) bones consist of the ilium, the ischium, and the pubis. Both the pubis andischium are further divided into their respective bodies and rami. The os coxae have been likened to apropeller with two oppositely bent blades with a central shaft (the acetabulum).

The pelvis contains two joints: the sacroiliac joint and the symphysis pubis. The sacroiliac joint is partsynovial (one-third) and part cartilage (two-thirds); the symphysis pubis consists of cartilaginous layers oneither side of an interpubic disk consisting of fibrocartilage. Fibrous ligaments such as the iliolumbarligament further stabilize the bony pelvis.

The microanatomy of the blood supply of the symphysis pubis is controversial; there is evidence thatblood vessels penetrate the dense connective tissue in rim of the fibrocartilage as well as the contiguousbones of the os coxae [9].

Bacteremia due to Staphylococcus aureus●

Bacteremia related to infection of intravascular catheters or other implanted devices●

Trauma (including athletic injuries, open fractures, and/or or instrumentation of the pelvic bones)●

Pressure ulcer(s) of the sacrum●

Obstetrical injuries or abortion●

Injection drug use●

Urogynecologic surgery, particularly involving procedures such as bladder suspension involvingplacement of bone anchors

●

Other pelvic surgical procedures, including prostatectomy or transrectal prostate biopsy [7]●

Cardiac catheterization, especially when performed via the inguinal/femoral site●

Pelvic radiation, especially if complicated by osteoradionecrosis●

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MICROBIOLOGY

Pathogens responsible for pelvic osteomyelitis vary depending on the pathogenesis of the infection.Hematogenous infections are commonly due to S. aureus (including methicillin-resistant S. aureus) [10],but almost any pathogen capable of causing primary or secondary bacteremia can cause ahematogenous infection in the bony pelvis [11]. Intravenous drug abusers who develop pubicosteomyelitis or septic sacroiliitis appear to have a higher propensity to have Pseudomonas aeruginosaas a causative pathogen [12]. Postoperative pelvic osteomyelitis infections and infections secondary todecubitus ulcers are commonly mixed infections due to bowel or perineal flora [13].


Overview — Patients with acute sacroiliitis or pubic osteomyelitis may have fever and severe pain;however, many bony infections of the pelvis present subacutely with or without associated fever. Physicalexamination may be useful when predisposing causes such as pressure ulcers are present and patientshave localized pain and tenderness over discrete sites such as the symphysis pubis or sacroiliac jointsand inguinal region. In other cases, pain may be poorly localized or accompanied by other confusingsymptoms such as antalgic gait, limp, hip or buttock pain, or inability to bear weight [14]. In patients withspinal cord injury, pain may be absent.

Several clinical aspects of pelvic osteomyelitis and septic arthritis warrant special emphasis [11,13,15-18]:

Osteitis pubis — Osteitis pubis is an idiopathic postoperative complication of suprapubic cystotomy.

There may be a long interval between a precipitating cause (such as trauma or surgery) and theonset of pelvic osteomyelitis, and fever may be absent. These factors may contribute to diagnosticdelay.

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Patients with pubic osteomyelitis initially develop an infection of the pubic symphysis that laterproduces osteomyelitis in adjacent pubic rami. Such patients characteristically have severe pelvicpain associated with point tenderness overlying the symphysis pubis. They usually also havedifficulty walking and manifest a characteristic wide-based waddling gait.

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Patients with pyogenic sacroiliitis and secondary pelvic osteomyelitis may have vague poorlylocalized pain or pain in the buttock or hip. However, focal tenderness on exam is usually presentwith pressure or percussion over the sacroiliac region [19].

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Patients with pelvic osteomyelitis may develop abscesses in soft tissues adjacent to the bony pelvisor infection may dissect into areas that are quite distant from the site of bony involvement. Forexample, pubic osteomyelitis can lead to bilateral abscesses in the adductor muscles of the thigh[17].

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Patients with this condition have bony destruction of the margins of the symphysis pubis, severe pelvicpain, and a characteristic wide-based waddling gait [20]. Osteitis pubis has been recognized as acomplication of a wide range of urologic and gynecologic surgical procedures. It has been described inassociation with pregnancy, hernia repairs, pyelonephritis, and presumed trauma in athletes [10,13].Sinus tracts, a characteristic manifestation of osteomyelitis, have been described in some patients. Feveris usually absent.

The pathogenesis of osteitis pubis is uncertain. Possible etiologies include infection, mechanical traumato the symphysis, local vascular damage, or reflex sympathetic dystrophy. Some experts believe that allcases of osteitis pubis are secondary to infection (eg, that osteitis pubis is synonymous with pubicosteomyelitis) [13]. Others believe that pubic osteomyelitis and osteitis pubis are separate conditions (ie,that osteitis pubis is not an infectious disease) [21]. Even though this controversy remains unresolved,the possibility of infection (osteomyelitis) should be carefully assessed in every patient with presumedosteitis pubis. (See "Osteitis pubis".)

Sacral osteomyelitis — Most commonly, sacral osteomyelitis arises from contiguous spread of infectionfrom deep (stage IV) pressure ulcers. It may also arise as a complication of open or laparoscopic pelvicsurgery [22,23], following pelvic radiation, spinal or anal surgery, after penetrating trauma such as agunshot wound, or in the setting of sacral fracture or epidural anesthesia [24].

DIAGNOSIS

Culture and/or histopathologic examination of a bone biopsy are required in order to make a definitivediagnosis of osteomyelitis. In general, rates of culture positivity are higher when cultures are obtained atthe time of surgical debridement. The utility of percutaneous bone biopsy in the setting of pelvicosteomyelitis is controversial; some centers report a low yield of cultures from such procedures. As anexample, in one report including 35 biopsies of the pelvis, a pathogen was identified in only 17 percent ofcases [25].

Compatible symptoms in the setting of relevant risk factors, together with positive blood cultures andradiographic evidence of osteomyelitis, may also be diagnostic. Aspiration and cultures of pus obtainedfrom abscesses that are contiguous to bony pelvic abnormalities may supplant the need for bone biopsyin some cases. (See "Osteomyelitis in adults: Clinical manifestations and diagnosis", section on'Diagnosis'.)

White blood counts, erythrocyte sedimentation rate, and measurement of C-reactive protein levels mayprovide clues to the presence of an infectious process in the bony pelvis. However, these tests lackspecificity in distinguishing bony infection from other noninfectious conditions such as seronegativespondyloarthropathies.

Plain radiography is not sensitive for detecting osteomyelitis, although it may be useful to exclude othercauses of pain such as tumor or fractures. Computed tomography (CT) is more sensitive than plain


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radiography in detecting pelvic osteomyelitis, pyogenic sacroiliitis, or early pubic osteomyelitis but is lesssensitive than magnetic resonance imaging (MRI). CT or ultrasound may be useful in detecting softtissue swelling and abscess formation in contiguous soft tissues, particularly when aspiration or drainageprocedures are planned. (See "Approach to imaging modalities in the setting of suspected nonvertebralosteomyelitis".)

MRI is the most sensitive radiographic modality for detection of pelvic osteomyelitis. Marrowabnormalities typical of osteomyelitis may be detected by MRI before lytic or other typical changes ofosteomyelitis appear. (See "Approach to imaging modalities in the setting of suspected nonvertebralosteomyelitis".)


Pelvic bone and joint infections can be difficult to distinguish from other mimics. For example, pubicosteomyelitis may rarely be confused with spermatic cord torsion [26]. Chronic recurrent multifocalosteomyelitis, a rare condition of unknown etiology that most often affects long bones, can affect thebony pelvis in rare cases, particularly in children and adolescents [27]. Postradiation changes, healingfractures, and a variety of pathological problems involving the hip can also be mimics of pelvicosteomyelitis. Obturator pyomyositis can rarely mimic pelvic osteomyelitis as well as lead to secondaryosteomyelitis of the ischio-pubic bones [28,29].

TREATMENT

Treatment of pelvic osteomyelitis consists of debridement of infected or necrotic tissues, in conjunctionwith antimicrobial therapy directed at the causative pathogens. (See "Osteomyelitis in adults: Clinicalmanifestations and diagnosis" and "Osteomyelitis associated with open fractures in adults" and"Osteomyelitis in adults: Treatment".)

In general, pelvic osteomyelitis associated with sacral decubitus ulcer(s) requires surgical debridementfor cure [6]. Often, tissue reconstruction is required following debridement and antimicrobial therapy[30,31]. In some circumstances, definitive debridement of advanced osteomyelitis associated withadjacent sacral decubitus ulcers is not be possible. For some cases, hemicorporectomy has beenperformed; morbidity and mortality in such cases is high [32].

For patients with osteomyelitis involving the ilium, acetabulum, or ischium, thorough debridement may bedifficult because of the proximity of overlying or adjacent structures such as the sacral plexus, and/orbecause of difficult access for areas deep within the pelvis. In addition, debridement of the symphysispubis may be associated with subsequent instability and gait problems.

For cases in which definitive debridement is not feasible, a long course of intravenous antibiotics (eg, sixto eight weeks) may be sufficient for cure [19]. Successful management of pubic osteomyelitis have been


















managed with antimicrobial therapy without extensive debridement (after needle biopsy demonstrated acausative pathogen) has been described [13,33,34].

Selection of antibiotic therapy should be guided by bone cultures obtained via open biopsy or aspiration.For cases in which such microbiology data is not available, empiric antibiotic therapy should includeactivity against staphylococci, gram-negative bacilli, and anaerobes. Reasonable regimens includevancomycin in combination with a third- or fourth-generation cephalosporin (such as ceftriaxone,ceftazidime, or cefepime) and metronidazole. An alternative regimen consists of vancomycin incombination with a carbapenem.

The optimal duration of antibiotic therapy for treatment of pelvic osteomyelitis is uncertain. Most expertsfavor continuing antimicrobial therapy at least until debrided bone has been covered by vascularized softtissue, which is usually at least six weeks from the last debridement.

OUTCOMES

Risk factors for treatment failure include fistula, malignancy, polymicrobial infection, and resistantorganisms [35]. In one review including 61 patients with chronic osteomyelitis who underwent surgicaldebridement, the recurrence rate was 11.5 percent [31]. In another retrospective cohort study including61 patients with pelvic osteomyelitis associated with pressure ulcer who underwent debridement and flapcoverage with antimicrobial therapy for 20 weeks, the rate of treatment failure was 23 percent [36].



SUMMARY

Pelvic osteomyelitis may arise hematogenously, secondary to trauma or surgery via directinoculation of pathogens into bone, or via contiguous spread of infection from soft tissues within oroutside the bony walls of the pelvis. (See 'Introduction' above.)

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Predisposing factors for pelvic osteomyelitis include bacteremia related to infection of implanteddevices, trauma, pressure ulcers, pelvic or urologic surgery, obstetrical procedures, and intravenousdrug abuse. (See 'Epidemiology' above.)

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There may be a long interval between a precipitating cause (such as trauma or surgery) and theonset of pelvic osteomyelitis, and fever may be absent. (See 'Clinical manifestations' above.)

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REFERENCES

1. Ukwu HN, Graham BS, Latham RH. Acute pubic osteomyelitis in athletes. Clin Infect Dis 1992;15:636.

2. Kaplon DM, Iannotti H. Prostatic capsular perforation with extravasation resulting in pubicosteomyelitis: a rare complication of KTP laser prostatectomy. J Endourol 2008; 22:2705.

3. Graham CW, Dmochowski RR, Faerber GJ, et al. Pubic osteomyelitis following bladder necksurgery using bone anchors: a report of 9 cases. J Urol 2002; 168:2055.

4. Dinan JJ. TWO CASES OF PRIMARY OSTEOMYELITIS OF THE PUBIC BONE. Can Med Assoc J1939; 41:436.

5. Guthrie R, Monk J. Osteomyelitis of the symphysis pubis: a complication of cardiac catheterisation.Br J Clin Pract 1989; 43:383.

6. Bodavula P, Liang SY, Wu J, et al. Pressure Ulcer-Related Pelvic Osteomyelitis: A NeglectedDisease? Open Forum Infect Dis 2015; 2:ofv112.

7. Albers LF, Korving JC, van Elzakker EPM, Roshani H. Osteomyelitis of the Pubic Symphysis AfterTransrectal Biopsies of the Prostate. Urology 2018; 121:29.

8. Dourakis SP, Alexopoulou A, Metallinos G, et al. Pubic osteomyelitis due to Klebsiella pneumoniaein a patient with diabetes mellitus. Am J Med Sci 2006; 331:322.

Osteitis pubis consists of bony destruction of the margins of the symphysis pubis, severe pelvic pain,and a characteristic wide-based waddling gait. Fever is usually absent. Osteitis pubis may occur as aresult of infection or noninfectious causes. (See 'Osteitis pubis' above.)

●

Culture and/or histopathological examination of a bone biopsy are required in order to make adefinitive diagnosis of osteomyelitis. Magnetic resonance imaging (MRI) is the most sensitiveradiographic modality for detection of pelvic osteomyelitis. (See 'Treatment' above.)

●

Treatment of pelvic osteomyelitis consists of debridement of infected or necrotic tissues and a longcourse of antimicrobial therapy directed at the causative pathogens. In some cases, thoroughdebridement may be anatomically difficult and/or may result in instability and secondary gaitproblems. In such cases, a long course of antimicrobial therapy without extensive debridement maybe sufficient. Pelvic osteomyelitis due to sacral decubitus ulcer generally requires surgicaldebridement for cure. (See 'Treatment' above.)

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9. da Rocha RC, Chopard RP. Nutrition pathways to the symphysis pubis. J Anat 2004; 204:209.

10. Cosma S, Borella F, Carosso A, et al. Osteomyelitis of the pubic symphysis caused by methicillin-resistant Staphylococcus aureus after vaginal delivery: a case report and literature review. BMCInfect Dis 2019; 19:952.

11. Highland TR, LaMont RL. Osteomyelitis of the pelvis in children. J Bone Joint Surg Am 1983;65:230.

12. Ross JJ, Hu LT. Septic arthritis of the pubic symphysis: review of 100 cases. Medicine (Baltimore)2003; 82:340.

13. Sexton DJ, Heskestad L, Lambeth WR, et al. Postoperative pubic osteomyelitis misdiagnosed asosteitis pubis: report of four cases and review. Clin Infect Dis 1993; 17:695.

14. Deore S, Bansal M. Pelvic Osteomyelitis in a Child - A Diagnostic Dilemma. J Orthop Case Rep2018; 8:86.

15. Takemoto RC, Strongwater AM. Pelvic osteomyelitis mimicking septic hip arthritis: a case report. JPediatr Orthop B 2009; 18:248.

16. Beaupré A, Carroll N. The three syndromes of iliac osteomyelitis in children. J Bone Joint Surg Am1979; 61:1087.

17. Yoshida S, Nakagomi K, Goto S. Abscess formation in the prevesical space and bilateral thighmuscles secondary to osteomyelitis of the pubis--basis of the anatomy between the prevesicalspace and femoral sheath. Scand J Urol Nephrol 2004; 38:440.

18. del Busto R, Quinn EL, Fisher EJ, Madhavan T. Osteomyelitis of the pubis. Report of seven cases.JAMA 1982; 248:1498.

19. Bindal M, Krabak B. Acute bacterial sacroiliitis in an adult: a case report and review of the literature.Arch Phys Med Rehabil 2007; 88:1357.

20. Beer E. Periostitis and ostitis of the symphysis and rami of the pubis following suprapubiccystotomies. Int J Med Surg 1924; 237:233.

21. Rosenthal RE, Spickard WA, Markham RD, Rhamy RK. Osteomyelitis of the symphysis pubis: aseparate disease from osteitis pubis. Report of three cases and review of the literature. J BoneJoint Surg Am 1982; 64:123.

22. Apostolis CA, Heiselman C. Sacral osteomyelitis after laparoscopic sacral colpopexy performedafter a recent dental extraction: a case report. Female Pelvic Med Reconstr Surg 2014; 20:e5.

23. Iavazzo C, Gkegkes ID. Osteomyelitis after robotically assisted laparoscopic sacral colpopexy. Acta



































Inform Med 2013; 21:143.

24. Wittum S, Hofer CK, Rölli U, et al. Sacral osteomyelitis after single-shot epidural anesthesia via thecaudal approach in a child. Anesthesiology 2003; 99:503.

25. Said N, Chalian M, Fox MG, Nacey NC. Percutaneous image-guided bone biopsy of osteomyelitisin the foot and pelvis has a low impact on guiding antibiotics management: a retrospective analysisof 60 bone biopsies. Skeletal Radiol 2019; 48:1385.

26. Charles P, Ackermann F, Brousse C, et al. [Spontaneous streptococcal arthritis of the pubicsymphysis]. Rev Med Interne 2011; 32:e88.

27. Zellali K, Benard E, Smokvina E, et al. Multifocal pelvic osteomyelitis in a child associated with cat-scratch disease: a case report and review of the literature. Paediatr Int Child Health 2019; 39:290.

28. de Bodman C, Ceroni D, Dufour J, et al. Obturator externus abscess in a 9-year-old child: A casereport and literature review. Medicine (Baltimore) 2017; 96:e6203.

29. Kiran M, Mohamed S, Newton A, et al. Pelvic pyomyositis in children: changing trends inoccurrence and management. Int Orthop 2018; 42:1143.

30. Rennert R, Golinko M, Yan A, et al. Developing and evaluating outcomes of an evidence-basedprotocol for the treatment of osteomyelitis in Stage IV pressure ulcers: a literature and woundelectronic medical record database review. Ostomy Wound Manage 2009; 55:42.

31. Dudareva M, Ferguson J, Riley N, et al. Osteomyelitis of the Pelvic Bones: A MultidisciplinaryApproach to Treatment. J Bone Jt Infect 2017; 2:184.

32. Janis JE, Ahmad J, Lemmon JA, et al. A 25-year experience with hemicorporectomy for terminalpelvic osteomyelitis. Plast Reconstr Surg 2009; 124:1165.

33. COVENTRY MB, MITCHELL WC. Osteitis pubis: observations based on a study of 45 patients.JAMA 1961; 178:898.

34. Choi H, McCartney M, Best TM. Treatment of osteitis pubis and osteomyelitis of the pubicsymphysis in athletes: a systematic review. Br J Sports Med 2011; 45:57.

35. Becker A, Triffault-Fillit C, Valour F, et al. Pubic osteomyelitis: Epidemiology and factors associatedwith treatment failure. Med Mal Infect 2019.

36. Andrianasolo J, Ferry T, Boucher F, et al. Pressure ulcer-related pelvic osteomyelitis: evaluation ofa two-stage surgical strategy (debridement, negative pressure therapy and flap coverage) withprolonged antimicrobial therapy. BMC Infect Dis 2018; 18:166.


































GRAPHICS

Anatomy of human pelvic bone



Daniel J Sexton, MD Grant/Research/Clinical Trial Support: Centers for Disease Control and Prevention; NationalInstitutes of Health [Healthcare epidemiology]. Consultant/Advisory Boards: Magnolia Medical Technologies [Medicaldiagnostics]; National Football League [Infection prevention]; Johnson & Johnson [Mesh-related infections]. EquityOwnership/Stock Options: Magnolia Medical Technologies [Medical diagnostics]. Denis Spelman, MBBS, FRACP,FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose







Daniel J Sexton, MD Grant/Research/Clinical Trial Support: Centers for Disease Control and Prevention; NationalInstitutes of Health [Healthcare epidemiology]. Consultant/Advisory Boards: Magnolia Medical Technologies [Medicaldiagnostics]; National Football League [Infection prevention]; Johnson & Johnson [Mesh-related infections]. EquityOwnership/Stock Options: Magnolia Medical Technologies [Medical diagnostics]. Denis Spelman, MBBS, FRACP,FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose




Vertebral osteomyelitis and discitis in adults - UpToDate



Vertebral osteomyelitis and discitis in adultsAuthors: Malcolm McDonald, PhD, FRACP, FRCPA, Trisha Peel, MD, MBBS Section Editor: Denis Spelman, MBBS, FRACP,FRCPA, MPH Deputy Editor: Elinor L Baron, MD, DTMH


Literature review current through: Feb 2020. | This topic last updated: Dec 17, 2019.

INTRODUCTION

Vertebral osteomyelitis most often occurs as a result of hematogenous seeding of one or more vertebralbodies from a distant focus [1]. Infection may also involve the adjacent intervertebral disc space, whichhas no direct blood supply in adults. Infection can also arise following surgery or injection of the discspace or via contiguous spread from adjacent soft tissue infection.

Vertebral osteomyelitis and discitis may occur together or independently. The diagnosis andmanagement of these two entities are similar in most patients. The term pyogenic spondylitis refers toeither vertebral osteomyelitis or discitis.

Issues related to vertebral osteomyelitis will be reviewed here. Issues related to other forms ofhematogenous osteomyelitis in adults are discussed separately. (See "Osteomyelitis in adults: Clinicalmanifestations and diagnosis", section on 'Hematogenous osteomyelitis'.)

Issues related to spinal epidural abscess and tuberculous spinal infections are discussed separately.(See "Spinal epidural abscess" and "Skeletal tuberculosis".)

EPIDEMIOLOGY

Vertebral osteomyelitis is primarily a disease of adults; most cases occur in patients >50 years old [2].The incidence increases with age. Men are affected approximately twice as often as women in most caseseries; the reason for this is not fully understood. Risk factors for vertebral osteomyelitis include injectiondrug use, infective endocarditis, degenerative spine disease, prior spinal surgery, diabetes mellitus,corticosteroid therapy, or other immunocompromised state. (See 'Pathogenesis' below.)

The annual incidence of hospitalization for vertebral osteomyelitis in the United States between 1998 and2013 rose from 2.9 to 5.4 per 100,000, with lengthy hospital stays and substantial, long-term burden forpatients and the health system [3]. Reasons for the increase in incidence include [1]:

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PATHOGENESIS

Mechanisms of infection — Bacteria can reach the bones of the spine by three basic routes (see"Pathogenesis of osteomyelitis"):

Potential sources of hematogenous or contiguous spread of infection include the genitourinary tract, skinand soft tissue (eg, injection drug use), respiratory tract, infected intravascular devices, postoperativewound infection, infective endocarditis, and dental infection. In many cases, the primary site of infectioncannot be identified [6]. Less common causes include infected native or prosthetic heart valve infections,direct spread from a ruptured esophagus, diverticular or renal abscesses, and infected aortic lesions(image 2) [7].

Vertebral osteomyelitis has been reported as a complication of lumbar puncture, myelography,translumbar aortography, chemonucleolysis, discography, facet joint corticosteroid injection [8], epiduralcatheter placement, and epidural corticosteroid injection [9].

Hematogenous spread — Hematogenous spread is by far the most common cause of vertebralosteomyelitis. Adult vertebral bone has abundant, highly vascular marrow with a sluggish but high-volume blood flow via nutrient vessels of the posterior spinal artery. With aging, these vesselsprogressively develop a characteristic "corkscrew" anatomy that may predispose to bacterialhematogenous seeding.

Bloodborne organisms that transit the vertebral marrow cavity can produce a spontaneous localsuppurative infection. Initiation of infection may be facilitated by recent or prior bone trauma withdisruption of normal architecture.

Segmental arteries supplying the vertebrae usually bifurcate to supply two adjacent end plates ofcontiguous vertebrae. Thus, hematogenous vertebral osteomyelitis often causes bone destruction in twoadjacent vertebral bodies and usually destroys their intervertebral disc. The lumbar vertebral bodies are

Increasing rates of bacteremia due to intravascular devices and other forms of instrumentation; anincreasing proportion of vertebral osteomyelitis is health care related and/or post-procedural (up toone-third of new cases) [4,5].

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Increasing age of the population●

Increasing number of patients on renal replacement therapy●

Increasing number of patients on immunosuppressive medications●

Hematogenous spread from a distant site or focus of infection●

Direct inoculation from trauma, invasive spinal diagnostic procedures, or spinal surgery (image 1)●

Contiguous spread from adjacent soft tissue infection●



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most often involved, followed by thoracic and, less commonly, cervical vertebrae. Hematogenous sacralosteomyelitis is rare.

Skip lesions with more than one level of spinal infection occur in less than 5 percent of reported cases.Noncontiguous epidural abscesses appear to be more common (10 percent) [10].

It was previously postulated that spread of infection might occur via vertebral veins known as Batsonplexus [11,12]; this theory has been discounted.

Contiguous spread — Contiguous spread of infection may occur from tissues adjacent to the spine,such as the aorta, esophagus, or bowel. In such cases, extension of infection is facilitated by absence ofa circumferential cartilage plate or a layer of subchondral compact bone [13].

Sacral osteomyelitis most commonly occurs as a complication of a sacral pressure ulcer, although it canfollow pelvic infection, trauma, and/or surgery. Typically, it is polymicrobial and restricted to cortical bone[14,15]. (See "Infectious complications of pressure-induced skin and soft tissue injury", section on'Osteomyelitis'.)

Extension of infection — Extension of infection posteriorly can lead to epidural abscess, subduralabscess, or meningitis (image 1). Extension of infection anteriorly or laterally can lead to paravertebral,retropharyngeal, mediastinal, subphrenic, retroperitoneal, or psoas abscess (image 3 and table 1).Development of epidural or paravertebral abscess is more common in the setting of gram-positiveinfection than gram-negative infection [16]. In addition, thoracic vertebral infections can extend into thepleural space to produce an empyema [17].

Infection can occur in spinal elements other than the vertebral bodies, including the posterior spinousprocesses, the facet joints, the pedicles, and, rarely, the odontoid process [18].

MICROBIOLOGY

Most patients have monomicrobial infection. The most common cause of vertebral osteomyelitis isStaphylococcus aureus, accounting for more than 50 percent of cases in most series from developedcountries. The relative importance of methicillin-resistant S. aureus as a cause of vertebral osteomyelitishas increased as the community and hospital proportion of S. aureus strains that are methicillin resistanthave increased.

Other causes of vertebral osteomyelitis include [19,20]:

Enteric gram-negative bacilli, particularly following urinary tract instrumentation●

Nonpyogenic streptococci, including viridans group, milleri group, Streptococcus bovis, andenterococci [21,22]

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Pyogenic streptococci, including groups B and C/G, especially in patients with diabetes mellitus (see●





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Geography also influences the organisms associated with vertebral osteomyelitis. Burkholderiapseudomallei (melioidosis) is a potential pathogen in patients from periequatorial regions, and Salmonellaand Entamoeba histolytica are occasional causes in sub-Saharan Africa or South America.

CLINICAL FEATURES

Symptoms and signs — The major clinical manifestation of vertebral osteomyelitis is pain; pain istypically localized to the infected disc space area and is exacerbated by physical activity or percussion tothe affected area. Pain may radiate to the abdomen, leg, scrotum, groin, or perineum.

Spinal pain usually begins insidiously and progressively worsens over several weeks to months. In oneseries of 64 patients with hematogenous vertebral osteomyelitis, the mean duration of symptoms was48±40 days [20]. The pain is often worse at night; initially, it may be relieved by bed rest. Pain may beabsent in patients with paraplegia.

Patients whose infections extend posteriorly into the epidural space may present with clinical features ofan epidural abscess; this often consists of focal and severe back pain, followed by radiculopathy, thenmotor weakness and sensory changes (including loss of bowel and bladder control and loss of perinealsensation), and eventual paralysis. The risk of severe neurologic deficit is increased in the presence ofepidural abscess, especially with thoracic or cervical spinal involvement [25]. (See "Spinal epiduralabscess".)

Fever is an inconsistent finding. One review noted a frequency of 52 percent [2]; lower rates have beennoted in other studies [26].

Local tenderness to gentle spinal percussion is the most useful clinical sign but is not specific. Back painis often accompanied by reduced mobility and/or spasm of nearby muscles. Rarely, a mass or spinaldeformity may be visible.

The physical examination should include palpation for a distended bladder (may reflect spinal cordcompression), evaluation for signs of psoas abscess (eg, flank pain and pain with hip extension), and acareful neurologic assessment of the lower limbs.

"Group B Streptococcus: Virulence factors and pathogenic mechanisms" and "Group C and group Gstreptococcal infection")

Pseudomonas aeruginosa, coagulase-negative staphylococci, and Candida spp, especially inassociation with intravascular access, sepsis, or injection drug use [20,23] (see "Candidaosteoarticular infections")

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Tuberculous infection (see "Skeletal tuberculosis")●

Brucellosis, especially Brucella melitensis in North Africa, the Mediterranean rim, and the MiddleEast [24] (see "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis")

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A careful general examination is essential to evaluate for potential sources of hematogenous spread;these include injection sites and recent skin or soft tissue infection.

Laboratory findings — The leukocyte count may be elevated or normal. Elevations in the erythrocytesedimentation rate (ESR), which can exceed 100 mm/h, and C-reactive protein (CRP) are observed inmore than 80 percent of patients [27-29].

If elevated, the ESR and CRP are useful for following the efficacy of therapy. (See 'Clinical and laboratorymonitoring' below.)

DIAGNOSIS

Vertebral osteomyelitis should be suspected in the setting of new or worsening back or neck pain,especially with fever, and/or presence of bloodstream infection or infective endocarditis (IE) [1]. It shouldalso be suspected in patients with fever and new peripheral neurologic symptoms (with or without backpain) and in patients with new back or neck pain following a recent episode of bacteremia (especially withS. aureus) or fungemia.

The diagnosis of vertebral osteomyelitis or discitis is established based on positive culture obtained fromcomputed tomography (CT)-guided biopsy of the involved vertebra(e) and/or disc space. The diagnosismay be inferred in the setting of clinical and radiographic findings typical of vertebral osteomyelitis andpositive blood cultures with a likely pathogen such as S. aureus. Similarly, the diagnosis may be inferredin the setting of histopathologic findings consistent with infection in the absence of positive culture data,particularly in the setting of recent antibiotic administration. For circumstances in which there are nopositive microbiologic cultures or Gram stains and a biopsy cannot be performed, the diagnosis may beinferred in the setting of suggestive clinical and typical radiographic findings and persistently elevatedinflammatory markers.

Back pain due to vertebral osteomyelitis may respond initially to bed rest and conservative measures,leading to the erroneous conclusion of minor trauma, muscle strain, or other noninfectious cause. Inaddition, a history of degenerative spinal disease or recent trauma sometimes obscures or delays thetrue diagnosis. In such cases a sedimentation rate (or serial sedimentation rates) can be useful; a normalresult is reassuring.

Suggested clinical approach — Initial evaluation of patients with suspected vertebral osteomyelitisbegins with careful history and physical examination; patients should have a thorough neurologic examand should be questioned about predisposing factors including presence of indwelling devices, recentinstrumentation, and injection drug use. Initial diagnostic tests include inflammatory markers (erythrocytesedimentation rate [ESR] and C-reactive protein [CRP]) and cultures (blood and urine), followed by spinalimaging (magnetic resonance imaging [MRI] preferred if available) (algorithm 1). (See 'Radiographicimaging' below.)

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Evaluation for surgery is warranted for patients with neurologic deficits, radiographic evidence of epiduralor paravertebral abscess, and/or cord compression (threatened or actual). Ongoing monitoring foremergence or progression of neurologic signs is essential. In one case-control study including 97patients with vertebral osteomyelitis and severe neurologic deficit, risk factors for neurologic deficitincluded epidural abscess and thoracic vertebral involvement [25]. (See 'Surgery' below.)

In the absence of the above conditions warranting surgical intervention, patients with radiographicevidence of vertebral osteomyelitis should undergo CT-guided needle biopsy of the affected bone andaspiration of abscess if present [19]. The specimens should be sent for bacterial (aerobic and anaerobic),fungal, and mycobacterial culture as well as histologic examination.

If possible, antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed. Clinicalexceptions include neurologic compromise and sepsis; in these circumstances, empiric antibiotic therapyis warranted [1]. (See 'Antimicrobial therapy' below.)

A needle biopsy may not be necessary in patients with clinical and radiographic findings typical ofvertebral osteomyelitis and positive blood cultures with a likely pathogen (such as S. aureus,Staphylococcus lugdunensis) or in patients with positive serology for Brucella (which is warranted forpatients with relevant risk factors) [1]. Similarly, a positive blood culture due to a gram-negative entericrod, P. aeruginosa, or other invasive pathogen is usually good evidence that the same pathogen is alsothe cause of the spinal infection. However, blood culture isolates do not always correlate with cultureresults from needle biopsy; therefore, needle biopsy is warranted for cases in which an alternate sourcefor the bacteremia is present or strongly suspected [23]. (See "Brucellosis: Epidemiology, microbiology,clinical manifestations, and diagnosis".)

If cultures of blood and the needle aspirate are negative and the clinical suspicion for vertebralosteomyelitis remains high (on the basis of clinical and radiographic findings), we advocate performing asecond biopsy. In one retrospective study including 136 patients with vertebral osteomyelitis in theabsence of bacteremia, first biopsy was positive in 43 percent of cases and a second biopsy in 40percent of cases; when combined with blood culture results, this approach led to microbiologicaldiagnosis in nearly 75 percent of cases [30]. Performing blood cultures immediately following biopsy doesnot appear to add any benefit.

If repeat biopsy specimens and initial blood cultures are nondiagnostic, we usually initiate empiric therapyas discussed below. If such therapy does not result in objective clinical improvement in three to fourweeks, a third percutaneous needle biopsy or an open surgical biopsy should be performed. Somesuggest that, if the first set of cultures is negative, open biopsy be pursued before starting antibiotictherapy [19]. (See 'Antimicrobial therapy' below.)

The individual clinical approach must include consideration of the location of the infection, the underlyinghealth of the patient, and the experience of the local surgeons.

Diagnostic tools — Diagnostic tools for vertebral osteomyelitis include cultures (blood and urine),












imaging studies, and biopsy.

Microbiology cultures — Blood and urine cultures should be obtained in all patients withsuspected vertebral osteomyelitis; they are positive in up to 50 of cases [20,23]. (See 'Suggested clinicalapproach' above.)

In the setting of positive blood cultures for gram-positive organisms, evaluation for concurrent IE iswarranted in patients with underlying valvular disease and/or new-onset heart failure. (See 'Evaluation forendocarditis' below.)

Radiographic imaging — MRI is the most sensitive radiographic technique for diagnosis ofvertebral osteomyelitis and epidural abscess [31]. CT is a reasonable alternative imaging modality whenMRI is not available. If neither CT nor MRI is available, plain films should be pursued; however, plainfilms typically demonstrate radiographic findings only after the disease has become advanced. If a plainfilm demonstrates vertebral osteomyelitis, additional imaging is still warranted to assess the extent ofdisease and presence of complications (epidural or paraspinal abscess). Radionuclide scanning may beuseful if MRI is contraindicated because of claustrophobia or presence of an implantable cardiac orcochlear device [1].

Magnetic resonance imaging – MRI is the most sensitive radiographic technique for diagnosisvertebral osteomyelitis [31]. Typical MRI findings in vertebral osteomyelitis include (image 4) [32,33]:

●

Decreased signal intensity in the vertebral bodies and disc and loss of endplate definition (T1-weighted images) (image 5).

•

Increased disc signal intensity; less often, increased vertebral body signal intensity (T2-weightedimages) (image 1).

•

Contrast enhancement of the vertebral body and disc (image 6). Ring enhancement ofparaspinal and epidural processes correlates with abscess formation, whereas homogeneousenhancement correlates with phlegmon formation.

•

Vertebral osteomyelitis rarely occurs without characteristic involvement of the intervertebral disc. Forcases in which the disc is spared, an erroneous diagnosis of malignancy or compression fracturemay be made [34].

MRI abnormalities consistent with osteomyelitis can be observed long before plain films becomeabnormal. In a review of 103 patients, MRI demonstrated changes suggestive of osteomyelitis in 91percent of patients with symptoms of less than two weeks duration and in 96 percent of those withsymptoms of more than two weeks duration [35].

False-negative MRI findings have been reported in patients with vertebral osteomyelitis and epiduralabscess, especially in those with concurrent meningitis or with long, linear abscesses lackingdiscrete margins [36]. False-positive results can occur with bone infarction or fracture.















Radiographic findings in the setting of tuberculous vertebral osteomyelitis overlap with those seen inthe setting of bacterial osteomyelitis. Extension into surrounding soft tissue tends to be moreprominent in tuberculosis (TB) of the spine, and some patients with spinal TB have vertebral bodyabnormalities in the absence of disc space involvement. These issues are discussed furtherseparately. (See "Skeletal tuberculosis", section on 'Radiography'.)

The role of follow-up MRI is discussed below. (See 'Role of imaging' below.)

Computed tomography – CT demonstrates findings of vertebral osteomyelitis before changes areapparent on plain films (image 7). CT is also useful for detecting bony sequestra or involucra,adjacent soft tissue abscesses (image 8), and in localizing the optimal approach for a biopsy (image9) [31].

●

Subtle abnormalities detected by CT, such as end plate irregularities, may not be specific forosteomyelitis, and early destructive changes may be missed. CT has a high false-negative rate forepidural abscess [31].

Plain radiography – Plain radiographs are often normal in the early phases of infection. Typicalfindings in vertebral osteomyelitis consist of destructive changes of two contiguous vertebral bodieswith collapse of the intervening disc space.

●

Bone destruction may not be apparent for three weeks or more after the onset of symptoms (image10) [19,37]. Rarely, infection is confined to a single vertebra and produces collapse of the vertebralbody, mimicking vertebral compression fracture [38,39].

Chest radiography is warranted in the setting of clinical suspicion for TB, but a normal chest filmdoes not reduce clinical suspicion of spinal TB. (See "Diagnosis of pulmonary tuberculosis in adults"and "Skeletal tuberculosis".)

Radionuclide scanning – Radioisotope studies may be useful adjuncts to diagnosis whenradiographic changes on plain films or CT scans are absent or equivocal and the suspicion forosteomyelitis is high. They are relatively sensitive but their specificity for infection is low.Radionuclide scanning may be useful when MRI is contraindicated [40].

●

Labeled-leukocyte scans are rarely useful for the diagnosis of vertebral osteomyelitis becauseabnormalities typically manifest as a nonspecific photopenic defect with a reduced uptake ofisotope [41].

•

Three-phase bone scintigraphy using labeled technetium is a relatively sensitive and specifictest, but it may produce false-positive results in patients with noninfectious disorders such asfracture. False-negative results also can occur early in infection or in cases in which boneinfarction accompanies bone infection.

•

Gallium imaging is a sensitive and specific radionuclide scanning technique for vertebral•

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Biopsy — In general, biopsy is warranted to confirm clinical and/or radiographic suspicion ofvertebral osteomyelitis and to establish a microbiologic and histologic diagnosis.

Biopsy material is obtained via an open procedure or needle biopsy by CT guidance (image 9). In onestudy of 92 patients with vertebral osteomyelitis who had a biopsy, open biopsies had a highermicrobiologic yield than needle biopsies (91 versus 53 percent) [45]. In a subsequent study including 129patients with vertebral osteomyelitis, open biopsy had a higher diagnostic yield (70 percent) than fineneedle aspirate (41 percent) or core biopsy (30 percent) [22]. In the setting of radiographic abnormality ofthe paravertebral soft tissue, diagnostic biopsy of this area may be reasonable even in the absence of aparavertebral abscess [46].

Clinicians should not be deterred from obtaining a biopsy if the patient has received antibiotics recently[45,47]. Prior antibiotic exposure is likely to reduce the yield, but not critically [48].

Samples should be sent for aerobic, anaerobic, mycobacterial, and fungal cultures and histopathology[19]. The sensitivity (measured by yield of positive cultures or Gram stain of aspirated material) variesbetween studies from a low of 50 percent [49] to a high of 73 to 100 percent [26,50].

Rarely, nucleic acid amplification testing may be useful if initial aerobic and anaerobic cultures arenegative [1]. In one study including 19 patients with discitis, amplification-based DNA analysis ofaspirated disc material correlated well with traditional culture methods [51]. A subsequent studydemonstrated the potential value of 16S rRNA gene polymerase chain reaction (PCR) assay of biopsymaterial/aspirates as an adjunct to culture, although there were some false-positive results [52].Contamination with skin flora is a potential problem with DNA-based diagnostic methods.

Additional tests — Additional diagnostic tests may be warranted based on epidemiologic factors;these include:

osteomyelitis. A typical positive test reveals intense uptake in two adjacent vertebrae with lossof the intervening disc space. In a series of 41 patients with suspected vertebral osteomyelitis,increased gallium uptake was detected in all of the 39 patients with biopsy-proven osteomyelitis;subsequent biopsy showed only degenerative changes in two patients with negative galliumscans [42].

Positron emission tomography (PET) scanning using 18-fluorodeoxyglucose (FDG), especiallywhen combined with CT (PET-CT), is highly sensitive, with a negative predictive value forvertebral osteomyelitis of close to 100 percent. The specificity is good but may be compromisedby the presence of tumor, degenerative spinal disease, and/or spinal implants [43]. In oneprospective study including 32 patients with suspected vertebral osteomyelitis who underwentboth MRI and fluorine-18-fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT), MRI was moreuseful for detection of epidural/spinal abscess and 18F-FDG-PET/CT was more useful fordetection of metastatic infection [44].

•

Brucellosis serology – Brucellosis serologic testing is warranted in the setting of unexplained fever,●


















Evaluation for endocarditis — Evaluation for concurrent IE is warranted in patients with underlyingvalvular disease and/or new-onset heart failure in the setting of positive blood cultures for gram-positiveorganisms [21,53,54]. This is warranted even though the duration of therapy for vertebral osteomyelitis(at least six weeks) is an adequate duration for treatment of IE in most cases. Patients with IE requireadditional follow-up evaluation for valvular disease as well as prophylactic antibiotics for prevention ofsubsequent IE. (See "Clinical manifestations and evaluation of adults with suspected left-sided nativevalve endocarditis", section on 'Echocardiography' and "Antimicrobial prophylaxis for the prevention ofbacterial endocarditis".)

A retrospective review including 91 cases of vertebral osteomyelitis (excluding TB, brucellosis, andculture-negative and postsurgical cases) identified 28 patients (31 percent) with IE [53]. When patientswith and without IE were compared, the following risk factors were significantly associated with coincidentIE:

IE was less likely in patients with a urinary tract–presumed source of infection and with infection due togram-negative organisms.


The differential diagnosis of vertebral osteomyelitis includes the following conditions; they are alldistinguished radiographically.

fatigue, and arthralgia in an individual with a possible source of exposure (eg, contact with animaltissues, ingestion of unpasteurized milk or cheese). Major endemic areas include countries of theMediterranean basin, Persian Gulf, the Indian subcontinent, and parts of Mexico and Central andSouth America. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, anddiagnosis".)

Tuberculosis – Diagnostic evaluation for TB is warranted in the setting of relevant risk factors; theseinclude a family history of TB, birth or long-term residence in a highly endemic region, HIV/AIDS,chest radiograph suggestive of latent TB infection, and/or diabetes. (See "Diagnosis of pulmonarytuberculosis in adults".)

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Age >75 years [21]●

Predisposing heart condition●

Heart failure●

Positive blood cultures●

Infection due to gram-positive organisms, especially nonpyogenic streptococci or staphylococci●

Spinal epidural abscess – Clinical manifestations of spinal epidural abscess include fever, back pain,and neurologic deficits. (See "Spinal epidural abscess".)

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TREATMENT

Management of vertebral osteomyelitis consists of antimicrobial therapy and percutaneous drainage ofparavertebral abscess(es) if present. Timely surgical intervention is usually warranted for patients withneurologic deficits, radiographic evidence of epidural or paravertebral abscess, and/or cord compression(threatened or actual).

During the course of treatment for vertebral osteomyelitis, the pace of progression can change suddenly,with potential for catastrophic complications. Therefore, close observation (especially in the first twoweeks after diagnosis) is essential. New neurologic manifestation(s), persistent back pain, and/orfeatures of sepsis require immediate investigation.

Antimicrobial therapy

Clinical approach — Selection of antimicrobial therapy should be tailored to results of biopsy or bloodculture.

If possible, antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed. Clinicalexceptions include neurologic compromise and sepsis; in these circumstances, empiric antibiotic therapyis warranted [1].

If blood and biopsy cultures are negative and the clinical suspicion for vertebral osteomyelitis is highbased on clinical and radiographic findings, initiation of empiric therapy is warranted. (See 'Empiric

Psoas abscess – Clinical manifestations of psoas abscess include back or flank pain, fever, and painwith hip extension. (See "Psoas abscess".)

Degenerative spine disease – Degenerative spine disease is common with aging, is associated withback pain, but does not usually result in radiculopathy. (See "Acute lumbosacral radiculopathy:Pathophysiology, clinical features, and diagnosis", section on 'Degenerative changes'.)

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Herniated disc – Clinical manifestations of disc herniation include back pain and radiculopathy. (See"Acute lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis", section on'Disc protrusion and level of injury'.)

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Metastatic tumor – Metastatic spinal tumor is typically associated with back pain in the setting ofknown malignancy; the most common primary cancers associated with skeletal metastasis includebreast, prostate, thyroid, lung, and renal cancer. (See "Evaluation of low back pain in adults", sectionon 'Serious systemic etiologies' and "Epidemiology, clinical presentation, and diagnosis of bonemetastasis in adults".)

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Vertebral compression fracture – Clinical manifestations of vertebral compression fracture consist ofacute onset of localized back pain in the setting of risk factors for osteoporosis. (See "Evaluation oflow back pain in adults", section on 'Less serious, specific etiologies'.)

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therapy' below.)

Pathogen-directed therapy — No randomized controlled studies have compared antibioticregimens for vertebral osteomyelitis. Choice of antibiotic therapy should be guided by biopsy or bloodculture results:

Staphylococcal spp – If the organism is found to be methicillin-susceptible Staphylococcus, werecommend treatment with an anti-staphylococcal penicillin such as nafcillin or oxacillin (2 gintravenously [IV] every 4 hours) or cefazolin (2 g IV every 8 hours); flucloxacillin is also anacceptable agent (not available in the United States).

●

If the Staphylococcus is methicillin resistant or if the patient is allergic to beta-lactam antibiotics, wefavor beta-lactam desensitization or treatment with vancomycin (15 to 20 mg/kg/dose every 8 to 12hours, not to exceed 2 g per dose). We do not use ceftriaxone as an alternative to cefazolin orantistaphylococcal penicillin in the absence of special circumstances (such as inability to givemultiple daily intravenous doses). For patients who are unable to tolerate vancomycin due to allergy,daptomycin (6 mg/kg IV once daily) is an acceptable alternative.

Streptococcal spp – If the streptococci is fully sensitive to penicillin (minimum inhibitory concentration[MIC] <0.12 mcg/mL), we recommend treatment with either ceftriaxone (2 g IV every 24 hours) orpenicillin G (12 to 18 million units/day by continuous infusion or in six divided daily doses).

●

If the Streptococcus has intermediate susceptibility to penicillin (MIC between 0.12 and 0.5 mcg/mL),we typically treat with ceftriaxone (2 g IV every 24 hours). Alternatively, penicillin (24 million units/dayper continuous infusion or in six divided daily doses) may be used. Patients with intermediate or fullyresistant streptococci should be treated in collaboration with an infectious disease specialist.Specialized in vitro testing may be needed to select an appropriate antibiotic regimen for infectionscaused by fully resistant streptococci.

Gram-negative bacilli – Choice of a specific agent for empiric therapy of gram-negative bacilli shouldbe based on knowledge of the prevailing pathogens (and susceptibility patterns) within the healthcare setting. Initial treatment with one of the following is appropriate:

●

Third-generation cephalosporin (ceftriaxone 2 g IV daily or ceftazidime 2 g IV every 8 hours orcefotaxime 2 g IV every 6 hours).

•

Fourth-generation cephalosporin (cefepime 2 g IV every 8 to 12 hours). Dosing every 12 hoursis sufficient in most cases; dosing every 8 hours is reasonable in patients with febrileneutropenia (particularly in the setting of known or suspected osteomyelitis due toPseudomonas spp).

•

Fluoroquinolone (ciprofloxacin 400 mg IV every 12 hours or 500 to 750 mg orally every 12hours).

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Empiric therapy — Patients with negative Gram stain and culture results should be treated with anantimicrobial regimen with activity against the common causes of vertebral osteomyelitis, includingstaphylococci, streptococci, and gram-negative bacilli.

An appropriate empiric regimen consists of vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not toexceed 2 g per dose) plus one of the following: cefotaxime (2 g IV every 6 hours), ceftazidime (1 to 2 gIV every 8 to 12 hours), ceftriaxone (2 g IV daily), cefepime (2 g IV every 12 hours), or ciprofloxacin (400mg IV every 12 hours or 500 to 750 mg orally twice daily).

Anaerobes are uncommon pathogens in patients with vertebral osteomyelitis, and we do not routinelyadd anaerobic coverage to initial empiric therapy. Such coverage is warranted if clinical features suggestthat the infection may be due to anaerobic organisms (such as in the setting of a concomitant intra-abdominal abscess) or if the Gram stain is positive but aerobic cultures are negative. In such cases,metronidazole (500 mg IV every six hours) may be added to the above regimen.

If empiric therapy does not result in objective clinical improvement (decreasing inflammatory markers,resolving fever and back discomfort) in three to four weeks, a repeat percutaneous needle biopsy or opensurgical biopsy is required (algorithm 1).

Duration of therapy and follow-up — We routinely treat for a minimum of six weeks, with carefulreview to determine if further treatment is required [1,55]. Longer duration of therapy (eight weeks insome cases) is warranted for patients with undrained paravertebral abscess(es) and/or infection due todrug-resistant organisms (including methicillin-resistant S. aureus [MRSA]) [56]. In some cases, up to 12weeks of therapy may be necessary, particularly in the setting of extensive bone destruction; the durationof therapy should be tailored to individual circumstances during the course of clinical follow-up. (See'Clinical and laboratory monitoring' below.)

The above approach to duration of therapy is supported by the following studies:

Cutibacterium (formerly Propionibacterium) acnes – For treatment of infection due to C. acnes, wefavor penicillin (20 to 24 million units IV daily by continuous infusion or in six divided doses) orceftriaxone (2 g IV every 24 hours). Patients allergic to beta-lactams may be treated withvancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose).

●

Fungal infection – Treatment of fungal vertebral osteomyelitis is discussed separately. (See"Candida osteoarticular infections".)

●

A randomized trial including 351 patients with vertebral osteomyelitis demonstrated that six weeks ofantibiotic treatment was not inferior to 12 weeks of antibiotic therapy with respect to the proportion ofpatients cured at one year [55]. The number of patients with abscesses in the trial was low (19percent), and computed tomography (CT)-guided drainage was needed in only 4 percent of cases. Inaddition, a short duration of intravenous therapy was administered (median 14 days); the mostcommon oral antibiotic regimen was a fluoroquinolone with rifampin. The trial did not include patientswith culture-negative infections. The most commonly isolated pathogen was S. aureus;

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Following at least two weeks of parenteral therapy, completion of treatment with oral therapy may bereasonable in the following circumstances [1,57,58]:

Oral antibiotic regimens for completing treatment of vertebral osteomyelitis are summarized in the table(table 2).

Patients with laboratory and radiographic evidence of treatment failure warrant repeat tissue biopsy (viaimage-guided aspiration or surgery) for microbiologic and histologic examination.

Clinical and laboratory monitoring — During antimicrobial therapy, patients should be followedcarefully for clinical signs of soft tissue extension, paraspinal abscess, and cord compression.

Patients should also be followed with weekly monitoring of inflammatory markers (erythrocytesedimentation rate [ESR] and C-reactive protein [CRP]) [1]. In one retrospective study including 44patients with vertebral osteomyelitis, those without a significant decline in the ESR during the first monthof therapy were more likely to fail medical therapy (9 of 18 cases compared with 3 of 26 cases with a >50percent fall in ESR) [28]. However, a rapid decline was not common: the ESR either rose or failed todecline during the first two weeks of treatment in 19 of 32 patients who were ultimately cured withmedical therapy. Similar findings have been reported by others [59]. CRP normalizes more rapidly thanthe ESR after successful treatment of spinal infections and after uncomplicated spinal fusion surgery [31].

Role of imaging — Routine follow-up imaging studies are not necessary. Regular imaging duringtreatment and in the presence of clinical improvement will not benefit the outcome. Magnetic resonanceimaging (MRI), CT, and plain films may appear to worsen for several weeks after the initiation of antibiotictherapy that will be ultimately successful [35].

Follow-up imaging studies are warranted in patients whose clinical status has not improved at theplanned time for discontinuation of antibiotics in order to evaluate for the presence of an abscess in needof drainage or to detect spinal instability amenable to surgical intervention [1].

fluoroquinolones are not regarded as ideal drugs for treatment of staphylococcal infections.

A retrospective review including 314 patients with vertebral osteomyelitis noted that independent riskfactors conferring an increased likelihood of relapse in patients treated <8 weeks included presenceof undrained paravertebral abscess(es) and MRSA infection; in the absence of these findings, thelikelihood of relapse in patients treated <8 weeks was much lower [56].

●

The infection is uncomplicated and the patient has no significant comorbidities.●

A favorable clinical response to initial parenteral therapy is observed.●

A suitable drug is available, with proven susceptibility to the causative organism and excellentbioavailability.

●

There is a high chance of reliable absorption of oral medication. Clinicians should check forconcomitant medication that may hinder absorption.

●

Compliance with oral therapy can be assured or carefully monitored.●

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The utility of obtaining imaging studies four to eight weeks after completion of treatment of vertebralosteomyelitis was examined in a retrospective study including 79 patients [60]; none of 27 patients whodemonstrated improvement in follow-up MRI studies had evidence of treatment failure after one year offollow-up. In contrast, 5 of 38 patients (13 percent) and 4 of 14 patients (29 percent) whose initial follow-up images demonstrated equivocal changes or evidence of radiographic worsening subsequently failedmedical treatment during long-term follow-up.

Associated hardware — Development of vertebral osteomyelitis in the presence of spinal hardwaretypically reflects a complication of the hardware placement. Most patients have an associated woundinfection, although rarely hematogenous seeding of hardware can occur. In such cases, treatment shouldbe based on culture data obtained from wound drainage and/or operative debridement. Typically suchinfections are treated with intravenous antimicrobial therapy tailored to culture results until bone fusionhas been achieved (at least six weeks). If removal of the hardware following union is feasible, repeatcultures should be obtained at the time of hardware removal to guide subsequent therapy, which typicallyincludes at least another six weeks of antimicrobial therapy. If hardware removal is not feasible,antimicrobial suppression (tailored to culture and susceptibility data) may be required either after or inlieu of a long course of parenteral therapy. Rarely oral therapy can be used as primary therapy if thecausative organism is susceptible to an oral agent such as fluoroquinolone.

Issues related to treatment of infections associated with hardware are discussed further separately. (See"Osteomyelitis in adults: Treatment", section on 'Presence of orthopedic hardware'.)

Surgery — Indications for surgery include [1,19]:

There are no randomized trials evaluating surgical management of vertebral osteomyelitis [1]. Placinghardware in the setting of spinal infection has raised concern regarding recurrent or chronic infection dueto adherence of bacteria to foreign material. It is common practice to administer an additional six-week'tail' of oral antibiotics, although there is little evidence to guide management. One retrospective studyhas indicated that, when spinal stabilization is required, timely instrumentation may be safe in the settingof appropriate selection and duration of antimicrobial therapy [61]. Another study reported outcomes for100 patients with vertebral osteomyelitis who underwent a variety of surgical procedures, which werehighly variable; approximately one-quarter of patients had residual pain and a similar proportion requiredrepeat surgery [62].

In contrast to the preceding study, a report of 42 patients with vertebral osteomyelitis who requiredsurgery, 40 had complete resolution of their deficits with no recurrences following a two-stage procedure

Presence of neurologic deficits●

Presence of epidural or paravertebral abscesses in need of drainage (see "Spinal epidural abscess")●

Threatened or actual cord compression due to vertebral collapse and/or spinal instability●

Progression, persistence, or recurrence of disease (as documented by persistently positive bloodcultures or worsening pain) despite appropriate antimicrobial therapy

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that included anterior debridement and strut grafting followed by delayed instrumented posterior fusions[63]. Patients received an average of 14.4 days of intravenous antibiotics after the anterior debridementand six weeks of intravenous therapy following the posterior instrumentation. (See 'Prognosis' below.)

In general, paravertebral abscess can be managed by CT-guided catheter drainage. Epidural abscess inthe setting of neurologic deficit should be managed with surgical intervention; this may include opendrainage, bone debridement, and interbody fusion (with or without bone grafting and posteriorinstrumentation). (See "Spinal epidural abscess".)

Adjunctive measures — Bed rest and analgesics are generally helpful in managing pain after thediagnosis is established. A fitted back brace often provides substantial back relief and enhances mobilityfor patients with severe pain. Clinicians should have a low threshold for referral to a specialist painservice.

Early bed rest may be particularly important, especially in lumbar osteomyelitis. When the patient isupright, the whole weight of the upper body is transmitted to the point of active infection. It is our practiceto put patients with severe pain to bed for at least 10 days and use intensive in-bed, non-weight bearingphysical therapy and long-acting oral analgesics. In such circumstances, prophylactic measures forprevention of deep venous thrombosis are warranted. (See "Prevention of venous thromboembolicdisease in acutely ill hospitalized medical adults".)

PROGNOSIS

The most serious complication of vertebral osteomyelitis is neurologic impairment secondary to eitherabscess formation or bony collapse. Most patients have gradual improvement in back pain after therapyis begun, and the pain typically disappears after bone fusion occurs. However, back pain can persist. Thebest way to reduce the morbidity and mortality associated with vertebral osteomyelitis is to minimize thetime between the onset of symptoms and the initiation of appropriate therapy.

The long-term outcome in vertebral osteomyelitis was evaluated in a retrospective study of 253 patientswith vertebral osteomyelitis with median duration of follow-up 6.5 years (range 2 days to 38 years) [64].Relapse occurred in 14 percent and residual symptoms occurred in 31 percent; 11 percent died (all-cause mortality). Surgery was performed in 43 percent of patients and was successful in 79 percent ofcases. Independent risk factors for death or residual symptoms included neurologic compromise at thetime of diagnosis (eg, motor weakness, spinal instability, paralysis), nosocomial acquisition of infection,and delay in diagnosis. The results of this study need to be interpreted with caution since cases werecollected over a long time period (1950 to 1994), which means that some cases occurred prior to thedevelopment of modern imaging and diagnostic techniques.

In another study including 260 patients with vertebral osteomyelitis, three-quarters of treatment failuresoccurred within 4.7 months of diagnosis [4]. Multivariate analysis indicated that infection with S. aureuswas associated with increased risk of relapse. Longer-term outcomes included neurological deficit (16



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percent) and persistent back pain (32 percent).

Major depression is a well-recognized complication of chronic back pain (about a third of patients) and isan important potential long-term consequence [65,66].

Overall morbidity and mortality tends to increase with age [67]; this may be related to delayed diagnosis(especially when people have background degenerative spinal disease or have communicationdifficulties), multiple comorbidities, and age-related frailty [68]. Older patients are also more likely to haveconcomitant infective endocarditis (IE); in one study including 351 patients with vertebral osteomyelitis(85 of whom were ≥75 years of age), IE was diagnosed in 37 percent of patients ≥75 years comparedwith 14 percent of patients <75 years [69].

Mortality — Prior to the discovery of antibiotics, vertebral osteomyelitis was fatal in approximately 25percent of cases [13]. Mortality due to vertebral osteomyelitis in the antibiotic era is less than 5 percent,and the rate of residual neurologic deficits among survivors is less than 7 percent. Delays in diagnosiscan lead to disabling complications [1].

In a large retrospective study including more than 7000 patients with vertebral osteomyelitis, in-hospitalmortality (6 percent) was largely determined by comorbidities including diabetes, end-stage kidneydisease, cirrhosis, and malignancy [70].


Links to society and government-sponsored guidelines from selected countries and regions around theworld are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infection inadults" and "Society guideline links: Outpatient parenteral antimicrobial therapy".)

SUMMARY

Vertebral osteomyelitis occurs by three basic routes: hematogenous spread from a distant site orfocus of infection (this is the most common mechanism), direct inoculation from trauma or spinalsurgery, and contiguous spread from adjacent soft tissue infection. (See 'Mechanisms of infection'above.)

●

The most important infecting organism in vertebral osteomyelitis is Staphylococcus aureus,accounting for more than 50 percent of cases. Other pathogens include nonpyogenic streptococci,pyogenic streptococci including groups B and C/G, enteric gram-negative bacilli, Candida spp,Pseudomonas aeruginosa, Brucella spp, and Mycobacterium tuberculosis. (See 'Microbiology'above.)

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The major clinical manifestation of vertebral osteomyelitis is back or neck pain, with or without fever.The most common clinical finding is local tenderness to percussion over the involved posterior

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REFERENCES

1. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA)Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis inAdults. Clin Infect Dis 2015; 61:e26.

2. Sapico FL, Montgomerie JZ. Pyogenic vertebral osteomyelitis: report of nine cases and review of

spinous processes. The most common laboratory abnormalities are elevated erythrocytesedimentation rate and C-reactive protein. (See 'Clinical features' above.)

Vertebral osteomyelitis should be suspected on the basis of clinical features and radiographicstudies (magnetic resonance imaging is the most sensitive radiographic technique) and confirmed bybiopsy of the infected intervertebral disc space or vertebral bone. Blood cultures are positive in up to50 to 70 percent of patients; a biopsy may not be necessary in patients with clinical and radiographicfindings typical of vertebral osteomyelitis and positive blood cultures with a likely pathogen. (See'Diagnosis' above.)

●

Every effort should be made to identify the pathogen(s) before starting antimicrobial treatment. Inpatients with suspected vertebral osteomyelitis, we favor the clinical approach described above andsummarized in the algorithm (algorithm 1). Evaluation for concurrent infectious endocarditis may bewarranted in select patients. (See 'Suggested clinical approach' above.)

●

Most cases of vertebral osteomyelitis respond to antimicrobial therapy. Surgery is necessary in aminority of patients with vertebral osteomyelitis; prompt surgery is warranted for patients with focalneurologic deficits, epidural or paravertebral abscess, and/or cord compression. (See 'Treatment'above and 'Surgery' above.)

●

If possible, antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed.Clinical exceptions include neurologic compromise and sepsis; in these circumstances, empiricantibiotic therapy is warranted. Choice of antibiotic therapy should be guided by biopsy or bloodculture results if available. For patients with negative culture results, empiric treatment is warrantedbased on the most likely organisms to cause infection. (See 'Clinical approach' above.)

●

We routinely treat for a minimum duration of six weeks. Longer duration of therapy (at least eightweeks) is warranted for patients with undrained paravertebral abscess(es) and/or infection due todrug-resistant organisms (including methicillin-resistant S. aureus). The duration of therapy shouldbe tailored to individual circumstances during the course of clinical follow-up. (See 'Duration oftherapy and follow-up' above.)

●









the literature. Rev Infect Dis 1979; 1:754.

3. Issa K, Diebo BG, Faloon M, et al. The Epidemiology of Vertebral Osteomyelitis in the UnitedStates From 1998 to 2013. Clin Spine Surg 2018; 31:E102.

4. Gupta A, Kowalski TJ, Osmon DR, et al. Long-term outcome of pyogenic vertebral osteomyelitis: acohort study of 260 patients. Open Forum Infect Dis 2014; 1:ofu107.

5. Pigrau C, Rodríguez-Pardo D, Fernández-Hidalgo N, et al. Health care associated hematogenouspyogenic vertebral osteomyelitis: a severe and potentially preventable infectious disease. Medicine(Baltimore) 2015; 94:e365.

6. Cahill DW, Love LC, Rechtine GR. Pyogenic osteomyelitis of the spine in the elderly. J Neurosurg1991; 74:878.

7. McHenry MC, Rehm SJ, Krajewski LP, et al. Vertebral osteomyelitis and aortic lesions: case reportand review. Rev Infect Dis 1991; 13:1184.

8. Falagas ME, Bliziotis IA, Mavrogenis AF, Papagelopoulos PJ. Spondylodiscitis after facet jointsteroid injection: a case report and review of the literature. Scand J Infect Dis 2006; 38:295.

9. Hooten WM, Mizerak A, Carns PE, Huntoon MA. Discitis after lumbar epidural corticosteroidinjection: a case report and analysis of the case report literature. Pain Med 2006; 7:46.

10. Ju KL, Kim SD, Melikian R, et al. Predicting patients with concurrent noncontiguous spinal epiduralabscess lesions. Spine J 2015; 15:95.

11. Batson OV. THE FUNCTION OF THE VERTEBRAL VEINS AND THEIR ROLE IN THE SPREADOF METASTASES. Ann Surg 1940; 112:138.

12. HENRIQUES CQ. Osteomyelitis as a complication in urology; with special reference to theparavertebral venous plexus. Br J Surg 1958; 46:19.

13. Kulowski J. Pyogenic vertebral osteomyelitis of the spine: An analysis and discussion of 102 cases.J Bone Joint Surg 1936; 1:343.

14. Larson DL, Hudak KA, Waring WP, et al. Protocol management of late-stage pressure ulcers: a 5-year retrospective study of 101 consecutive patients with 179 ulcers. Plast Reconstr Surg 2012;129:897.

15. Türk EE, Tsokos M, Delling G. Autopsy-based assessment of extent and type of osteomyelitis inadvanced-grade sacral decubitus ulcers: a histopathologic study. Arch Pathol Lab Med 2003;127:1599.

16. Park KH, Cho OH, Jung M, et al. Clinical characteristics and outcomes of hematogenous vertebral


































osteomyelitis caused by gram-negative bacteria. J Infect 2014; 69:42.

17. Bass SN, Ailani RK, Shekar R, Gerblich AA. Pyogenic vertebral osteomyelitis presenting asexudative pleural effusion: a series of five cases. Chest 1998; 114:642.

18. Michel-Batôt C, Dintinger H, Blum A, et al. A particular form of septic arthritis: septic arthritis of facetjoint. Joint Bone Spine 2008; 75:78.


20. Nolla JM, Ariza J, Gómez-Vaquero C, et al. Spontaneous pyogenic vertebral osteomyelitis innondrug users. Semin Arthritis Rheum 2002; 31:271.

21. Murillo O, Grau I, Gomez-Junyent J, et al. Endocarditis associated with vertebral osteomyelitis andseptic arthritis of the axial skeleton. Infection 2018; 46:245.

22. Chong BSW, Brereton CJ, Gordon A, Davis JS. Epidemiology, Microbiological Diagnosis, andClinical Outcomes in Pyogenic Vertebral Osteomyelitis: A 10-year Retrospective Cohort Study.Open Forum Infect Dis 2018; 5:ofy037.

23. Patzakis MJ, Rao S, Wilkins J, et al. Analysis of 61 cases of vertebral osteomyelitis. Clin OrthopRelat Res 1991; :178.

24. Koubaa M, Maaloul I, Marrakchi C, et al. Spinal brucellosis in South of Tunisia: review of 32 cases.Spine J 2014; 14:1538.

25. Lemaignen A, Ghout I, Dinh A, et al. Characteristics of and risk factors for severe neurologicaldeficit in patients with pyogenic vertebral osteomyelitis: A case-control study. Medicine (Baltimore)2017; 96:e6387.

26. Torda AJ, Gottlieb T, Bradbury R. Pyogenic vertebral osteomyelitis: analysis of 20 cases andreview. Clin Infect Dis 1995; 20:320.

27. Beronius M, Bergman B, Andersson R. Vertebral osteomyelitis in Göteborg, Sweden: aretrospective study of patients during 1990-95. Scand J Infect Dis 2001; 33:527.

28. Carragee EJ, Kim D, van der Vlugt T, Vittum D. The clinical use of erythrocyte sedimentation rate inpyogenic vertebral osteomyelitis. Spine (Phila Pa 1976) 1997; 22:2089.


30. Gras G, Buzele R, Parienti JJ, et al. Microbiological diagnosis of vertebral osteomyelitis: relevanceof second percutaneous biopsy following initial negative biopsy and limited yield of post-biopsy


































blood cultures. Eur J Clin Microbiol Infect Dis 2014; 33:371.

31. An HS, Seldomridge JA. Spinal infections: diagnostic tests and imaging studies. Clin Orthop RelatRes 2006; 444:27.

32. Dagirmanjian A, Schils J, McHenry M, Modic MT. MR imaging of vertebral osteomyelitis revisited.AJR Am J Roentgenol 1996; 167:1539.

33. Ledermann HP, Schweitzer ME, Morrison WB, Carrino JA. MR imaging findings in spinal infections:rules or myths? Radiology 2003; 228:506.

34. Kayani I, Syed I, Saifuddin A, et al. Vertebral osteomyelitis without disc involvement. Clin Radiol2004; 59:881.

35. Carragee EJ. The clinical use of magnetic resonance imaging in pyogenic vertebral osteomyelitis.Spine (Phila Pa 1976) 1997; 22:780.

36. Post MJ, Quencer RM, Montalvo BM, et al. Spinal infection: evaluation with MR imaging andintraoperative US. Radiology 1988; 169:765.

37. Gold RH, Hawkins RA, Katz RD. Bacterial osteomyelitis: findings on plain radiography, CT, MR,and scintigraphy. AJR Am J Roentgenol 1991; 157:365.

38. Abe E, Yan K, Okada K. Pyogenic vertebral osteomyelitis presenting as single spinal compressionfracture: a case report and review of the literature. Spinal Cord 2000; 38:639.

39. Markus HS. Haematogenous osteomyelitis in the adult: a clinical and epidemiological study. Q JMed 1989; 71:521.

40. Censullo A, Vijayan T. Using Nuclear Medicine Imaging Wisely in Diagnosing Infectious Diseases.Open Forum Infect Dis 2017; 4:ofx011.

41. Palestro CJ, Torres MA. Radionuclide imaging in orthopedic infections. Semin Nucl Med 1997;27:334.

42. Hadjipavlou AG, Cesani-Vazquez F, Villaneuva-Meyer J, et al. The effectiveness of gallium citrateGa 67 radionuclide imaging in vertebral osteomyelitis revisited. Am J Orthop (Belle Mead NJ) 1998;27:179.

43. Palestro CJ. Radionuclide imaging of osteomyelitis. Semin Nucl Med 2015; 45:32.

44. Kouijzer IJE, Scheper H, de Rooy JWJ, et al. The diagnostic value of 18F-FDG-PET/CT and MRI insuspected vertebral osteomyelitis - a prospective study. Eur J Nucl Med Mol Imaging 2018; 45:798.

45. Marschall J, Bhavan KP, Olsen MA, et al. The impact of prebiopsy antibiotics on pathogen recoveryin hematogenous vertebral osteomyelitis. Clin Infect Dis 2011; 52:867.


































46. Chang CY, Simeone FJ, Nelson SB, et al. Is Biopsying the Paravertebral Soft Tissue as Effectiveas Biopsying the Disk or Vertebral Endplate? 10-Year Retrospective Review of CT-Guided Biopsyof Diskitis-Osteomyelitis. AJR Am J Roentgenol 2015; 205:123.

47. Saravolatz LD 2nd, Labalo V, Fishbain J, et al. Lack of effect of antibiotics on biopsy culture resultsin vertebral osteomyelitis. Diagn Microbiol Infect Dis 2018; 91:273.

48. Kim CJ, Song KH, Park WB, et al. Microbiologically and clinically diagnosed vertebral osteomyelitis:impact of prior antibiotic exposure. Antimicrob Agents Chemother 2012; 56:2122.

49. Rawlings CE 3rd, Wilkins RH, Gallis HA, et al. Postoperative intervertebral disc space infection.Neurosurgery 1983; 13:371.

50. McGahan JP, Dublin AB. Evaluation of spinal infections by plain radiographs, computedtomography, intrathecal metrizamide, and CT-guided biopsy. Diagn Imaging Clin Med 1985; 54:11.

51. Lecouvet F, Irenge L, Vandercam B, et al. The etiologic diagnosis of infectious discitis is improvedby amplification-based DNA analysis. Arthritis Rheum 2004; 50:2985.

52. Choi SH, Sung H, Kim SH, et al. Usefulness of a direct 16S rRNA gene PCR assay ofpercutaneous biopsies or aspirates for etiological diagnosis of vertebral osteomyelitis. DiagnMicrobiol Infect Dis 2014; 78:75.

53. Pigrau C, Almirante B, Flores X, et al. Spontaneous pyogenic vertebral osteomyelitis andendocarditis: incidence, risk factors, and outcome. Am J Med 2005; 118:1287.

54. Koslow M, Kuperstein R, Eshed I, et al. The unique clinical features and outcome of infectiousendocarditis and vertebral osteomyelitis co-infection. Am J Med 2014; 127:669.e9.

55. Bernard L, Dinh A, Ghout I, et al. Antibiotic treatment for 6 weeks versus 12 weeks in patients withpyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet2015; 385:875.

56. Park KH, Cho OH, Lee JH, et al. Optimal Duration of Antibiotic Therapy in Patients WithHematogenous Vertebral Osteomyelitis at Low Risk and High Risk of Recurrence. Clin Infect Dis2016; 62:1262.

57. Babouee Flury B, Elzi L, Kolbe M, et al. Is switching to an oral antibiotic regimen safe after 2 weeksof intravenous treatment for primary bacterial vertebral osteomyelitis? BMC Infect Dis 2014; 14:226.

58. Li HK, Rombach I, Zambellas R, et al. Oral versus Intravenous Antibiotics for Bone and JointInfection. N Engl J Med 2019; 380:425.

59. Khan MH, Smith PN, Rao N, Donaldson WF. Serum C-reactive protein levels correlate with clinical


































response in patients treated with antibiotics for wound infections after spinal surgery. Spine J 2006;6:311.

60. Kowalski TJ, Berbari EF, Huddleston PM, et al. Do follow-up imaging examinations provide usefulprognostic information in patients with spine infection? Clin Infect Dis 2006; 43:172.

61. Park KH, Cho OH, Lee YM, et al. Therapeutic outcomes of hematogenous vertebral osteomyelitiswith instrumented surgery. Clin Infect Dis 2015; 60:1330.

62. Valancius K, Hansen ES, Høy K, et al. Failure modes in conservative and surgical management ofinfectious spondylodiscitis. Eur Spine J 2013; 22:1837.

63. Dimar JR, Carreon LY, Glassman SD, et al. Treatment of pyogenic vertebral osteomyelitis withanterior debridement and fusion followed by delayed posterior spinal fusion. Spine (Phila Pa 1976)2004; 29:326.

64. McHenry MC, Easley KA, Locker GA. Vertebral osteomyelitis: long-term outcome for 253 patientsfrom 7 Cleveland-area hospitals. Clin Infect Dis 2002; 34:1342.

65. Von Korff M, Crane P, Lane M, et al. Chronic spinal pain and physical-mental comorbidity in theUnited States: results from the national comorbidity survey replication. Pain 2005; 113:331.

66. Demyttenaere K, Bruffaerts R, Lee S, et al. Mental disorders among persons with chronic back orneck pain: results from the World Mental Health Surveys. Pain 2007; 129:332.

67. Zarrouk V, Gras J, Dubée V, et al. Increased mortality in patients aged 75 years or over withpyogenic vertebral osteomyelitis. Infect Dis (Lond) 2018; 50:783.

68. Amadoru S, Lim K, Tacey M, Aboltins C. Spinal infections in older people: an analysis ofdemographics, presenting features, microbiology and outcomes. Intern Med J 2017; 47:182.

69. Courjon J, Lemaignen A, Ghout I, et al. Pyogenic vertebral osteomyelitis of the elderly:Characteristics and outcomes. PLoS One 2017; 12:e0188470.

70. Akiyama T, Chikuda H, Yasunaga H, et al. Incidence and risk factors for mortality of vertebralosteomyelitis: a retrospective analysis using the Japanese diagnosis procedure combinationdatabase. BMJ Open 2013; 3.






























GRAPHICS

Discitis lumbar spine and epidural abscess on T2-weighted MRI

A T2-weighted image of the lumbar spine (A) shows an epidural abscess (arrow) extending from theabnormal disc space between L1 and L2 (arrowhead). There is increased signal in the disc. Image Bis a magnified view and shows the epidural abscess (arrow) and an abnormal, high intensity disc(arrowhead). The patient received an epidural injection two weeks prior to presentation.





Osteomyelitis lumbar spine s/p AAA repair

A lateral examination of the lumbar spine (A) shows erosive scalloping of the L2 and L3vertebral bodies (arrows). Image B is a magnified view of an abscess (arrow) surrounding theaortic graft (arrowhead) and eroding into the vertebral body (dashed arrow). Image C is abone window of L3 that shows destruction of the vertebral body by the perigraft abscess.

s/p: status post; AAA: abdominal aortic aneurysm.




Vertebral osteomyelitis causing a psoas abscess on CT

Image A is a CT scan through the lower abdomen and shows bony destruction of alumbar vertebral body (arrow) with a swollen right psoas muscle (arrowhead).Image B is a CT scan through the upper pelvis and shows an abscess in the rightpsoas muscle (arrow).

CT: computed tomography.




Complications of vertebral osteomyelitis

Short-term complications Longer-term complications

Epidural abscess, subdural abscess, meningitisParaspinal abscess and extension (including psoas,retropharyngeal, mediastinal, subphrenic, retroperitonealabscesses, or empyema)Extension of infection involving the aorta and/or venacavaSpinal cord and/or nerve root impingement withneurological consequencesVertebral body collapseEndocarditis*

Residual neurological deficit(s)Chronic back painDepression

* In general, vertebral osteomyelitis is a complication of bacteremia; associated endocarditis may or may not be present.




Clinical approach to vertebral osteomyelitis in adults



ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; MRI: magnetic resonance imaging; CT: computed tomography.* Additional diagnostic testing may be warranted based on epidemiologic factors (eg, to evaluate for infection due to brucellosis or tub discitis in adults for discussion.¶ Refer to the UpToDate topic on vertebral osteomyelitis and discitis in adults for discussion of characteristic radiographic findings, dif Δ A needle biopsy may not be necessary in patients with clinical and radiographic findings typical of vertebral osteomyelitis and positiv vertebral osteomyelitis and discitis in adults for further discussion.◊ Biopsy material should be sent for bacterial (aerobic and anaerobic) culture, fungal culture, and mycobacterial culture in addition to




Three magnetic resonance images of vertebral osteomyelitis due to methicillin-resistant Staphylococcus aureus

(A) T2-weighted axial image shows collections in the psoas muscles bilaterally (arrows) representingabscesses.(B) T2-weighted sagittal image demonstrates increased signal in the L2/3 and L3/4 intervertebral discspaces (arrows).(C) Post-contrast sagittal fat saturated T1-weighted image shows enhancement in the intervertebraldisc spaces (arrows) and adjacent L2 to L4 vertebral bodies (arrowheads).

Courtesy of Jenny Hoang, MBBS, Duke University Medical Center.




Osteomyelitis lumbar spine on T1-weighted MRI

A T1-weighted image of the lumbar spine (A) shows decreased signal intensity of the vertebralbodies (arrows) and loss of endplate definition (arrowhead). Image B is a magnified view of the ill-defined low intensity disc (arrowhead). There is poor definition of the disc with the low intensity endplates (arrows).





Osteomyelitis lumbar spine on T1 contrast-enhanced MRI

A contrast-enhanced MRI of the lumbar spine (A) shows enhancement of the end plates and thevertebral bodies (arrows). Image B is a magnified view of the lumbar spine showing enhancement ofthe opposing endplates and vertebral bodies (arrows).





Vertebral osteomyelitis on CT

Image A is a sagittal reconstruction of the lumbar spine showing disc space widening (arrow) andsubtle destruction of the opposing endplates not appreciated on plain radiograph. Image B showsmore advanced destruction of bone on either side of the joint space (arrows).





Vertebral osteomyelitis and paravertebral abscess on CT

Image A is an axial CT through the thorax showing vertebral bony destructionwith a paravertebral abscess (arrow head). In image B, the paravertebralabscess is overlaid in orange.





Aspiration of a paravertebral abscess under CT guidance

Image A is a CT scan with the patient in left decubitus position and shows a right-sided paravertebralabscess. Image B shows the tip of the needle as it advances toward the abscess.





Cervical osteomyelitis on radiograph and MRI

Image A is a lateral radiograph of the spine showing bony destruction of C4 (arrow) and C5(arrowhead) with kyphosis. Image B is a T1-weighted MRI sequence with fat saturation followinggadolinium and shows enhancement of C4 and C5 (arrows) and their posterior elements (arrowhead).



¶

Δ

◊

Δ

◊

§



Oral antibiotic regimens for completing treatment of vertebral osteomyelitis in adults*


Staphylococci, methicillinsusceptible


Rifampin plus one of thefollowing:

300 to 450 mg twice daily

Levofloxacin 500 to 750 mg once daily

Ciprofloxacin 500 to 750 mg twice daily

Fusidic acid (whereavailable)

500 mg three times daily

Clindamycin 300 to 450 mg three times daily

Staphylococci, methicillin resistant One of the following:

Rifampin plus one of thefollowing:

300 to 450 mg twice daily



Fusidic acid (whereavailable)

500 mg three times daily


Linezolid 600 mg twice daily

Gram-negative organisms One of the following:




Penicillin-sensitive streptococci One of the following:

Amoxicillin 750 to 1000 mg three times daily


The doses recommended above are intended for adults with normal renal function; the doses of some of these agentsmust be adjusted in patients with renal insufficiency. Refer to the Lexicomp drug-specific monographs for renal doseadjustments.

* Following at least two weeks of parenteral therapy, completion of treatment with oral therapy may be reasonable in somecircumstances; refer to UpToDate for further discussion.¶ The choice of antibiotic regimen should be based on susceptibility, as well as patient drug allergies, intolerances, and potentialdrug-drug interactions or contraindications to a specific agent.Δ Rifampin should not be used alone; it must be combined with a second agent to reduce the likelihood of selection for drugresistance.◊ Fusidic acid is not available in the United States. Fusidic acid should not be used alone; it must be combined with a secondagent to reduce the likelihood of selection for drug resistance. When rifampicin is combined with fusidic acid, fusidic acid levelsmay be reduced.§ Ciprofloxacin and levofloxacin have activity against Pseudomonas aeruginosa. For P. aeruginosa the higher dose range offluoroquinolone should be used; ciprofloxacin 750 mg every 12 hours or levofloxacin 750 mg once daily.¥ Oral amoxicillin therapy may be considered after an initial period of intravenous therapy for the management of penicillin-susceptible streptococci.

Reference:1. Pushkin R, Iglesias-Ussel MD, Keedy K, et al. A randomized study evaluating oral fusidic acid (CEM-102) in combination

with oral rifampin compared with standard-of-care antibiotics for treatment of prosthetic joint infections: a newlyidentified drug-drug interaction. Clin Infect Dis 2016; 63:1599.

Data from:

¶

Δ

◊

Δ

◊

§

§

¥

[1]



1. Société de Pathologie Infectieuse de Langue Français (SPILF). Primary infectious spondylitis and following intradiscalprocedure, without prosthesis. Recommendations. Med Mal Infect 2007; 37:573.

2. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines forthe diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015; 61:e26.

3. Bernard L, Dinh A, Ghour I, et al Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebralosteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet 2015; 385:875.

4. Li H-K, Rombach I, Zambellas R, Oral versus Intravenous Antibiotics for Bone and Joint Infection. NEJM 2019; 380:425.



Malcolm McDonald, PhD, FRACP, FRCPA Nothing to disclose Trisha Peel, MD, MBBS Consultant/Advisory Boards:Merck Sharp & Dohme [Infections in intensive care units (Ceftolozane/tazobactam)]. Denis Spelman, MBBS, FRACP,FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose







Malcolm McDonald, PhD, FRACP, FRCPA Nothing to disclose Trisha Peel, MD, MBBS Consultant/Advisory Boards:Merck Sharp & Dohme [Infections in intensive care units (Ceftolozane/tazobactam)]. Denis Spelman, MBBS, FRACP,FRCPA, MPH Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose




Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis - UpToDate

https://www.uptodate.com/...stations-and-diagnosis?search=osteomyelitis&topicRef=7668&source=see_link#PATIENT_INFORMATION[19.03.2020 15:31:39]

Authors: Elie Berbari, MD, FIDSA, Larry M Baddour, MD, FIDSA, FAHA, Antonia F Chen, MD, MBA Section Editor: DenisSpelman, MBBS, FRACP, FRCPA, MPH Deputy Editor: Elinor L Baron, MD, DTMH



Literature review current through: Feb 2020. | This topic last updated: Sep 16, 2019.

INTRODUCTION

Prosthetic joint infection (PJI) is a serious complication of prosthetic joint implantation [1-8]. Theepidemiology, microbiology, clinical manifestations, and diagnosis of PJI will be reviewed here.Infections associated with other implanted orthopedic devices, such as pins and rods, will not bespecifically discussed, but similar principles may apply.

Issues related to treatment and prevention of PJIs are discussed separately. (See "Prosthetic jointinfection: Treatment" and "Prevention of prosthetic joint and other types of orthopedic hardwareinfection".)

EPIDEMIOLOGY

Nearly one million total hip arthroplasties (THAs) or total knee arthroplasties (TKAs) are performed inthe United States each year. It is estimated that, by 2030, nearly two million THAs or TKAs will beperformed in the United States annually [9].

The risk of PJI is greater for knee arthroplasty than hip arthroplasty [1,10]. The rate of PJI in mostcenters ranges between 0.5 to 2 percent for knee replacements, 0.5 to 1.0 percent for hipreplacements, and <1 percent for shoulder replacements [11,12]. The higher rate of PJI in kneearthroplasties may be attributable to greater mobility in the joint and soft tissue and less protective softtissue coverage.

PJI rates appear to be declining. In a retrospective study including more than 10,700 patients in Taiwanwho underwent primary TKA between 2002 and 2014, the rate of PJI declined from 1.9 percent (2002to 2006) to 0.76 percent (2011 to 2014) [13]. Similarly, in a review including more than 11,800 patientsin the United States who underwent primary THA or TKA, the incidence of PJI between 2008 and 2016fell from 1.4 to 0.6 percent [14]. In another cohort including more than 679,000 patients in the UnitedKingdom who underwent primary TKA between 2003 and 2013, the infection rate was 0.5 percent [15].

In general, the rate of PJI is highest during the first two years following surgery [1]. In one studyinvolving more than 69,000 patients undergoing elective TKA followed longitudinally from 1997 to 2006,

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the rate of PJI during the first two years following surgery was 1.5 percent; the rate of PJI 2 to 10 yearsafter joint replacement was 0.5 percent [16].

Risk factors — Risk factors for PJI include [1,17-24]:

DEFINITIONS

PJIs are often categorized as early onset (<3 months after surgery), delayed onset (3 to 12 monthsafter surgery), and late onset (>12 months after surgery). However, these definitions are controversialand not always clear-cut, particularly in patients for whom the diagnosis is delayed [26]. There isconsiderable overlap between early- and delayed-onset PJIs, and hip PJIs tend to occur sooner thanknee PJIs.

The timing of infection onset has implications for surgical management (eg, implant retention versusremoval). These issues are discussed further separately. (See "Prosthetic joint infection: Treatment".)

MICROBIOLOGY

Pathogens — The timing of infection can be a clue as to the identity of the infecting organism. Early-onset infections are often due to S. aureus, gram-negative bacilli, anaerobes, or polymicrobial infection[1]. Delayed-onset infections are often due to coagulase-negative staphylococci, Cutibacterium(Propionibacterium) species, or enterococci. Late-onset infections are often due to S. aureus, gram-negative bacilli, or beta-hemolytic streptococci. (See 'Clinical manifestations' below.)

In the setting of PJI due to coagulase-negative staphylococci, species identification may be useful insome circumstances. For example, Staphylococcus lugdunensis is a coagulase-negativeStaphylococcus that shares some aspects of virulence with S. aureus but is often susceptible to beta-lactam antibiotics, including oxacillin [27]. (See "Staphylococcus lugdunensis".)

Cutibacterium acnes is a relatively common cause of PJI following shoulder arthroplasty (16 percent inone study) but is a rare cause of infection following hip or knee arthroplasty [28-30]. Cutibacterium

Presence of comorbidities such as rheumatoid arthritis, diabetes mellitus, malignancy, chronickidney disease, obesity, lymphedema, immunosuppression

●

Use of prednisone, tumor necrosis factor inhibitors, and other biologic disease-modifyingantirheumatic drugs

●

Prior arthroplasty or prior infection at the surgical site●

American Society of Anesthesiologists score ≥3 (table 1)●

Prolonged duration of surgery●

Postoperative complications such hematoma, wound dehiscence●

Staphylococcus aureus bacteremia [25]●


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avidum has been observed as a cause of hip PJI, and colonization of the groin in obese patients maybe a risk factor for hip PJI [31,32]. (See "Invasive Cutibacterium (formerly Propionibacterium)infections", section on 'Orthopedic infection'.)

Rare causes of PJI include fungal infection (most often Candida spp) and mycobacterial infection(Mycobacterium tuberculosis and rapidly growing mycobacteria). (See "Skeletal tuberculosis", sectionon 'Prosthetic joint infection' and "Rapidly growing mycobacterial infections: Mycobacteria abscessus,chelonae, and fortuitum", section on 'Prosthetic device infection'.)

Cultures are negative in 7 to 39 percent of patients with suspected PJI [33]. In general, cultures arecommonly positive in the setting of early-onset PJI, but frequently negative in patients who presentindolently with a loose, painful prosthesis. Cultures may be negative if insufficient tissue is sent forculture or if only swabs are obtained. In addition, antibiotic administration prior to culture collectiondiminishes culture yield [1,34]. In some cases, "culture-negative" PJI may be attributable to smallcolony variants of staphylococci, due to slow growth of these variants [35]. Fastidious pathogensassociated with culture-negative PJI include Coxiella burnetii, brucellosis, bartonellosis, mycoplasma,mycobacteria, and fungi [36].

Biofilm — Presence of orthopedic hardware enhances susceptibility to infection due to formation of abiofilm [37,38]. The process of biofilm formation consists of bacterial adherence to hardware, followedby multiplication and elaboration of exopolysaccharides ("glycocalyx"); over time, microcolonies ofbacteria encased in glycocalyx coalesce to form biofilm [39,40].

Bacteria near the surface of the biofilm are usually metabolically active and have access to nutrientsthat diffuse through the upper surface. Bacteria deep within the biofilm are metabolically inactive or invarious stages of dormancy and are protected from host defenses [39].

The microenvironment within a biofilm may adversely affect antimicrobial mechanisms, and diffusion ofantimicrobial agents through biofilm may be limited or slow [40]. Soon after a biofilm is established, thesusceptibility of bacteria to antimicrobial agents often demonstrates a logarithmic decline [41]. In thepresence of biofilm, antibiotic administration may be associated with an initial clinical response,followed by relapse within days or months of stopping antibiotic therapy, unless the hardware isremoved.

Presence of organisms in biofilm may explain the propensity of PJI to manifest weeks or months aftersurgery. It may also explain the difficulty associated with pathogen identification in patients withindolent, late-onset PJIs.

Given the slow metabolic rate of organisms in biofilm, suppressive antibiotic therapy may be successfulin some cases; however, such therapy may ultimately fail in the absence of hardware removal.



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Signs and symptoms — The clinical manifestations of PJI depend on the timing of symptom onset:early onset (<3 months after surgery), delayed onset (3 to 12 months after surgery), or late onset (>12months after surgery).

Early-onset infection is usually acquired during implantation. Less commonly, it can arise in the settingof postoperative wound dehiscence with contiguous spread of organisms from the superficial wound tothe deeper structures. These infections are frequently associated with hematoma formation orsuperficial necrosis of the incision. Most early-onset infections present with the acute onset of one ormore of the following findings: joint pain, warmth, erythema, induration or edema at the incision site,wound drainage or dehiscence, joint effusion, and fever.

Delayed-onset infection is often acquired during implantation; it typically presents with an indolentcourse characterized by persistent joint pain, with or without early implant loosening. Fever is present inless than half of cases [1]. Sinus tract associated with intermittent drainage may be observed; thisfinding on its own may be considered diagnostic of PJI [3]. In the absence of a sinus tract, physicalexam findings are often minimal; if swelling is present, it is usually slight. Delayed-onset infections maybe difficult to distinguish from aseptic failure of the prosthetic joint. PJI is often associated withpersistent joint pain, while mechanical loosening commonly causes pain with joint motion and weightbearing (which abates with rest) [42,43]. (See 'Differential diagnosis' below.)

Late-onset PJI often occurs in the setting of hematogenous seeding from infection at another site (suchas vascular catheter, urinary tract, or soft tissue infection) [44]. Patients with late-onset PJI typicallypresent with acute onset of systemic symptoms associated with bacteremia (similar to early-onsetinfection), including joint pain in a previously well-functioning joint, warmth, erythema, induration oredema at the incision site, joint effusion, and fever. Dislocation may occur [45]. It is not always possibleto determine whether a PJI arose hematogenously; in one study including 50 cases of hematogenousPJI, the median time of onset was nearly five years after surgery and a distant source for the infectionwas identified in only approximately half of the cases [46].

The timing of infection may be an important clue as to the identity of the infecting organism. (See'Microbiology' above.)

Asymptomatic infection — Asymptomatic PJI may be detected incidentally in the setting of revisionsurgery for other indications [47]. In one study including more than 600 hip or knee arthroplasty revisionsurgeries, PJI (defined as two or more positive cultures with the same organism) was diagnosed in 10percent of cases [48].

DIAGNOSIS

Clinical approach — PJI should be suspected patients with a joint prosthesis and relevant signs andsymptoms of infection (including joint pain, warmth, erythema, induration, or edema at the incision site,sinus tract or persistent wound drainage, wound dehiscence, joint effusion, or fever) [5].












The diagnosis of PJI can be challenging because the definition is not standardized; a number ofdiagnostic criteria have been proposed, including the 2018 International Consensus Meeting (ICM)criteria, the 2013 ICM criteria, the 2013 Infectious Disease Society of America guidelines, and the 2011Musculoskeletal Infection Society (MSIS) criteria (table 2) [4-8]. We favor the MSIS 2011 diagnosticcriteria, which are used most widely. (See 'Synovial fluid analysis' below.)

In general, the diagnosis rests on a combination of factors including history and physical examination,synovial fluid analysis, serum inflammatory markers, culture data, and intraoperative findings [2].Discriminating between chronic PJI and aseptic joint failure can be challenging. (See 'Differentialdiagnosis' below.)

The diagnosis of PJI may be established in any of the following circumstances [4,5] (see 'Interpretingtest results' below):

Findings suggestive of PJI include prosthesis with surrounding purulence and histopathologicexamination of periprosthetic tissue demonstrating acute inflammation [5]. However, these findings arenonspecific and may be observed with alternative etiologies including metallosis and inflammatoryarthritis. (See 'Differential diagnosis' below.)

For cases in which a definitive diagnosis of PJI cannot be made, additional data (including seruminflammatory markers and synovial fluid examination) may provide supportive evidence regarding thelikelihood of infection (table 2):

Presence of a sinus tract that communicates with the prosthesis●

Two or more periprosthetic cultures with phenotypically identical organisms (≥2 intraoperativecultures or a combination of preoperative synovial fluid aspiration culture and intraoperative tissueculture)

●

A single positive culture with a virulent organism (such as S. aureus) may also represent PJI.•

A single culture due to an organism of relatively low virulence (such as Staphylococcusepidermidis, Corynebacterium species, Cutibacterium species, or Bacillus species) is generallyconsidered a contaminant. Such organisms may be presumed to represent a true pathogen ifthe same organism is observed in multiple cultures; these cases should be evaluated in thecontext of other available evidence (such as intraoperative Gram stain or tissue biopsy).

•

Routine serum inflammatory markers include erythrocyte sedimentation rate (ESR) and C-reactiveprotein (CRP) [1-3]. Less commonly used serum markers that may warrant further study include D-dimer, procalcitonin, and interleukin-6 [49]. (See 'Serum inflammatory markers' below.)

●

Routine synovial fluid analysis consists of cell count with differential, Gram stain, aerobic andanaerobic culture, and crystal analysis [4,5,42]. Less commonly used synovial fluid markers thatmay warrant further study include alpha-defensin, leukocyte esterase, and CRP [50]. (See

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Obtaining diagnostic studies

Initial evaluation — In the setting of suspected PJI, initial diagnostic evaluation consists of plainradiography (to evaluate for alternative causes of pain and instability) and measurement of seruminflammatory markers (ESR and CRP) [49]. (See 'Radiographic imaging' below and 'Seruminflammatory markers' below.)

Thereafter, diagnostic arthrocentesis should be performed, unless the diagnosis of PJI is evidentclinically (eg, in the setting of a sinus tract) and definitive surgical debridement is planned [4,5,42]. Iffeasible, antimicrobial therapy should be withheld for at least two weeks prior to collecting specimensfor culture [34].

Knee and shoulder joint aspiration often can be performed at the bedside; hip joint aspiration frequentlyrequires guidance by ultrasound or fluoroscopy. If difficulty is encountered in obtaining synovial fluid,irrigation with sterile saline may be performed to obtain fluid for culture [51].

Synovial fluid should be sent for cell count with differential, Gram stain, aerobic and anaerobic culture,and crystal analysis [4,5,42]. Mycobacterial and fungal cultures should be submitted for patients withchronic, indolent, or refractory infection; previously culture-negative infection; or immunosuppression[2,52].

Synovial fluid may be sent for culture in a sterile tube (ideally a red-top tube with no additives and atube with an anticoagulant such as ethylenediaminetetraacetic acid to guard against clotting) or in bloodculture bottles. If blood culture bottles are used, synovial fluid also should also be sent in a sterilecontainer for Gram stain. Use of blood culture bottles may increase the likelihood of recoveringnonpathogenic skin contaminants; in such cases, culture results should be interpreted in the context ofthe Gram stain result. (See 'Microbiology studies' below and 'Synovial fluid analysis' below and "Septicarthritis in adults", section on 'Obtaining clinical specimens'.)

In patients with a sinus tract, drainage (collected by aspiration) should be sent for culture; swabs fromthe sinus tract should be not be sent given discordance with deep cultures [42,53]. In patients with feveror other systemic manifestations of infection, blood cultures (two sets) should be obtained.

Intraoperative evaluation — Intraoperative purulence may be attributable to PJI, in the absence ofother causes; alternative etiologies include crystal-associated arthritis and metallosis. (See 'Differentialdiagnosis' below.)

Intraoperative specimens should consist of at least three periprosthetic tissue samples (ideally five, tominimize sampling error and optimize specificity) obtained with different instruments and put intoseparate sterile containers, to ensure that there is no cross-contamination between specimens. Thesamples should be sent for culture (aerobic and anaerobic) and frozen section histology; tissue Gramstain need not be sent routinely (it has high specificity but low sensitivity for diagnosis of PJI) [54-56].

'Synovial fluid analysis' below.)







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Inoculation of periprosthetic tissues into blood culture bottles has been associated with highersensitivity compared with cultures using conventional plates and broth media [57-59]. (See'Microbiology studies' below and 'Histopathology' below.)

If pus is encountered, it should be aspirated in a sterile tube and sent for culture. Swab cultures shouldbe avoided given low sensitivity [42].

Mycobacterial and fungal cultures should be submitted for patients with chronic, indolent, or refractoryinfection; previously culture-negative infection; or immunosuppression [2,52].

If the prosthesis is explanted, sonication (eg, to dislodge biofilm) may be performed, followed by cultureof sonication fluid. (See 'Culture-negative infection' below.)

Interpreting test results

Microbiology studies — The microbiology of PJI is discussed above. (See 'Microbiology' above.)

The diagnosis of PJI may be established in the setting of two or more periprosthetic cultures withphenotypically identical organisms (a combination of preoperative synovial fluid aspiration culture andintraoperative tissue culture or ≥2 intraoperative tissue cultures) [4,5]. (See 'Clinical approach' above.)

A single positive culture with a virulent organism (such as S. aureus) may also represent PJI [60]. Asingle culture due to an organism of relatively low virulence (such as S. epidermidis, Corynebacteriumspp, Cutibacterium spp, or Bacillus spp) is generally considered a contaminant. If the same organism isobserved in multiple cultures, it may be presumed to represent a true pathogen; such cases should beevaluated in the context of other available evidence [1].

Synovial fluid culture has high sensitivity and specificity for diagnosis of PJI (72 and 95 percent,respectively, in one systematic review) [61]. The sensitivity of periprosthetic tissue culture is variable(65 to 94 percent) [42,62]. Use of saline irrigation to obtain cultures may reduce the culture specificity[63].

Sinus tract culture findings must be correlated with other data, since results may reflect skin floracontamination.

Synovial fluid analysis — Synovial fluid should be sent for cell count with differential, Gram stain,aerobic and anaerobic culture, and crystal analysis [4,5,42]. Less commonly used synovial fluidmarkers that may warrant further study include synovial fluid alpha-defensin, leukocyte esterase, andCRP [50].

For cases in which a definitive diagnosis of PJI cannot be made, synovial fluid analysis may be used (inconjunction with serum inflammatory markers) as supportive evidence regarding the likelihood ofinfection. (See 'Clinical approach' above.)

The approach to interpretation of synovial fluid analysis depends in part on the timing of clinical














presentation. In the setting of early-onset PJI, the synovial fluid cell count is often >10,000 cells/microL(>90 percent neutrophils). In the setting of delayed- and late-onset PJI, the synovial fluid cell count isoften >3000 cells/microL (80 percent neutrophils).

The interpretation of synovial fluid markers in the context of other clinical factors has not beenstandardized; a number of criteria have been proposed (table 2) [4-8]. We favor the MSIS 2011diagnostic criteria, which are used most widely. The ICM 2018 diagnostic criteria proposed a score-based definition for PJI with inclusion of synovial fluid parameters as minor criteria; however, thesecriteria include use of alpha-defensin and synovial fluid leukocyte esterase, which are not routinelyavailable.

Cell count and polymorphonuclear leukocytes (PMN) thresholds have been observed to differ slightlybetween chronic total knee arthroplasty infection (1100 to 3000 cells/microL, 64 to 75 percent PMNs)and chronic total hip arthroplasty (THA) infection (745 to 3000 cells/microL, 74 to 80 percent PMNs)[43,63-68]. In a retrospective study including 337 patients with suspected PJI, the most accurate cellcount threshold for patients with knee PJI was 1630 cells/microL (sensitivity and specificity 84 and 82percent, respectively) with 60 percent neutrophils (sensitivity and specificity 80 and 77 percent,respectively) [69]. The most accurate cell count threshold for patients with hip PJI was 2582cells/microL (sensitivity and specificity 80 and 85 percent, respectively) with 66 percent neutrophils(sensitivity and specificity 82 percent). Use of saline irrigation to obtain synovial fluid may confound thecell count.

Synovial fluid alpha-defensin may be useful for diagnosis of PJI. In one prospective study including 156patients with suspected PJI, the sensitivity, specificity, positive predictive value, and negative predictivevalue were 97, 97, 88, and 99 percent, respectively [70] (based on the 2014 International ConsensusGroup definition) [6]. An lateral flow assay for measurement of synovial fluid alpha-defensin(Synovasure lateral flow test) was approved by the United States Food and Drug Administration in2019; however, it uncertain whether this test is more useful for prediction of PJI than cell count withdifferential. In a meta-analysis including 10 studies and more than 750 patients with suspected PJI, thesensitivity and specificity of the test for diagnosis of PJI were 78 and 91 percent, respectively [71].

Serum inflammatory markers — Routine serum inflammatory markers include ESR and CRP [1-3];less commonly used serum markers that may warrant further study include D-dimer, procalcitonin, andinterleukin-6 [49].

For cases in which a definitive diagnosis of PJI cannot be made, serum inflammatory markers may beused (in conjunction with synovial fluid analysis) as supportive evidence regarding the likelihood ofinfection. (See 'Clinical approach' above.)

The approach to interpretation of serum inflammatory markers depends in part on the timing of clinicalpresentation. In the setting of early-onset PJI, ESR is not useful; CRP is often >100 mg/L. In the settingthe setting of delayed and late onset PJI, ESR is often >30 mm/hour and CRP is often >10 mg/L.



https://www.uptodate.com/contents/prosthetic-joint-infection-epidemiology-microbiology-clinical-manifestations-and-diagnosis/abstract/43,63-68









The interpretation of serum inflammatory markers in the context of other clinical factors has not beenstandardized; a number of criteria have been proposed (table 2) [4-8]. We favor the MSIS 2011diagnostic criteria, which are used most widely.

Following joint replacement surgery, the CRP may require two to three weeks to return to normalpreoperative values, and the ESR may require up to a year to return to normal preoperative values [72].Serum inflammatory markers must also be interpreted with caution in the setting of coexistent chronicinflammatory disease, which can also elevate serum inflammatory markers.

In a meta-analysis including 30 studies and more than 3900 revision arthroplasties, sensitivity andspecificity of ESR and CRP for diagnosis of PJI were 75 and 88 percent and 70 and 74 percent,respectively [49]. Combined use of ESR and CRP has been associated with sensitivity of 96 percent[66,73]; if both tests are negative, the likelihood of PJI is low. However, PJI may be present in thesetting of normal ESR and CRP; factors associated with such cases include infection due to pathogensof low virulence, prior antibiotic use, and immunosuppression [3].

Radiographic imaging — Radiographic imaging may be of value but usually does not provide adefinitive diagnosis of PJI. In general, plain radiographs should be performed in the setting of suspectedPJI; these are useful to screen for prosthetic loosening and fracture but lack sensitivity and specificityfor diagnosis of PJI [2].

The following plain radiography findings may be observed in the setting of PJI: abnormal lucency largerthan 2 mm in width at the bone-cement interface, changes in the position of prosthetic components,cement fractures, periosteal reaction, or motion of components on stress views [74]. These findings arecorrelated with the duration of infection; three to six months may be required before manifestation ofsuch changes. In addition, these changes are not specific for infection; they are also seen frequentlywith aseptic processes.

Other studies such as leukocyte scans, positron emission tomography (PET) scans, computedtomography (CT) scans, magnetic resonance imaging (MRI) scans, or bone scans are not useful forroutine diagnostic evaluation in most cases of suspected PJI [5].

Scintigraphy (such as technetium-colloid scans or gallium-67 labeled white blood cell scans) is rarelyuseful in early infection; scans may be falsely abnormal for up to 12 months following surgery due toperiprosthetic bone remodeling [75]. In addition, technetium-colloid scans can be positive in the settingof aseptic loosening. A normal scintigraphy study can be considered evidence against the presence ofinfection (high sensitivity), but a positive study is not definitive for establishing the diagnosis of PJI (lowspecificity).

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is not useful within the first year ofarthroplasty due to false-positive results associated with postoperative inflammation [76]. In asystematic review including 11 studies evaluating the diagnostic utility of PET for imaging patients withsuspected PJI, the pooled sensitivity and specificity of FDG-PET was 82 and 86 percent, respectively














[77]. The accuracy of PET scan was higher in THA infection and when criteria for PJI werepredetermined.

Use of CT scan is limited by imaging artifacts caused by metallic implants, and MRI can be performedonly with implants that are safe for this modality, such as those composed of titanium or tantalum [42].Some MRI scanners have metal suppression modalities (Metal Artifact Reduction Sequence) thatpermit greater resolution and an improved recognition of prosthesis failure, with or without infection [76].

Histopathology — Histopathologic examination of periprosthetic tissue may be performed toevaluate for infiltration of polymorphonuclear cells, indicative of an acute inflammatory reactionsupporting a diagnosis of PJI. This is often done as a frozen section; it may also be done via standardhistopathologic examination. The threshold number of PMNs per high-power field (HPF; 400xmagnification) to distinguish PJI from aseptic failure is uncertain; a threshold of at least five PMNs perHPF has been used (sensitivity and specificity >80 percent and >90 percent, respectively) [1-3]. In onemeta-analysis, histopathology had a pooled diagnostic odds ratio of 54.7 (95% CI 31.2-95.7) fordiagnosis of PJI [55]; however, sensitivity of the test is limited (18 to 67 percent) [78-83].

Culture-negative infection — For patients with suspected PJI and negative cultures from synovial fluidand periprosthetic tissue, repeat joint aspiration should be attempted. If feasible, antimicrobial therapyshould be withheld for at least two weeks prior to collecting specimens for culture. In addition to aerobicand anaerobic cultures, mycobacterial and fungal cultures should be submitted [2,52]. In the setting ofsuspected delayed-onset PJI, extended culture incubation (at least 14 days) may increase culturesensitivity (especially for recovery of Cutibacterium spp) [84,85].

Additional tools for diagnosis of culture-negative PJI include explant sonication, molecular diagnostictesting, and serologic testing.

Sonication of an explanted prosthesis can improve the yield of microbiologic diagnosis compared withtissue culture, especially in the setting of perioperative antibiotics [86,87]. In one meta-analysisincluding 12 studies, pooled sensitivity and specificity were 80 and 95 percent, respectively [87].Sonication is not routinely available in many microbiology laboratories; vortexing an explantedprosthesis is a reasonable alternative [88].

Nucleic acid amplification tests may be useful when routine cultures are negative and clinical suspicionfor PJI is high [89-94]. Many of these assays are based on detection of 16S rRNA gene(s) using avariety of polymerase chain reaction (PCR) techniques to evaluate sonicate fluid, synovial fluid, andjoint tissue [95]. The results must be interpreted carefully and correlated with Gram stains and clinicaland epidemiologic findings, since small amounts of contaminating bacterial material can lead to a false-positive result [92]. Metagenomic shotgun sequencing is a novel method under development forextracting, sequencing, and identifying nucleic acid as an alternative to PCR [96].

In the setting of relevant epidemiologic risk factors for infection due to C. burnetii or Brucella spp (eg,travel history, environmental or animal exposure), serologic tests to evaluate for infection due to these


















organisms should be performed. (See "Clinical manifestations and diagnosis of Q fever" and"Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)


PJI must be differentiated from mechanical and aseptic problems:


Links to society and government-sponsored guidelines from selected countries and regions around theworld are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infectionin adults".)

Aseptic loosening – Hardware loosening occurs due to wear of the prosthetic components.Persistent joint pain is suggestive of infection, whereas pain with joint motion and weight bearing(which abates with rest) is suggestive of hardware loosening. (See "Complications of total hiparthroplasty", section on 'Aseptic loosening'.)

●

Dislocation – Dislocation refers to an injury that forces the prosthesis out of position. Clinicalmanifestations include pain, difficulty moving the joint, and deformity of the joint area.Uncommonly, dislocation can occur in the setting of PJI, most frequently in the setting of late-onsetinfection. The presence of dislocation is established radiographically. (See "Complications of totalhip arthroplasty", section on 'Dislocation'.)

●

Gout and pseudogout – Gout (monosodium urate crystal deposition disease) and pseudogout(calcium pyrophosphate crystal deposition [CPPD] disease) are characterized by severe pain,erythema, edema, and warmth. The diagnosis of gout is established by visualization of uric acidcrystals in synovial fluid; the diagnosis of pseudogout is established by visualization of CPPDcrystals in synovial fluid. (See "Clinical manifestations and diagnosis of gout" and "Clinicalmanifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease".)

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Hemarthrosis – Hemarthrosis refers to bleeding into a joint due to traumatic or nontraumaticcauses. It is characterized by pain, swelling, warmth, and impaired mobility; the diagnosis isestablished by joint aspiration. (See "Overview of hemarthrosis".)

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Osteolysis – Osteolysis refers to bone resorption as a biologic response to particulate debris due towear of the prosthetic components. The diagnosis is established radiographically. (See"Complications of total hip arthroplasty", section on 'Osteolysis and wear'.)

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Metallosis – Metallosis refers to reactive synovitis to metallic debris. Synovial fluid cell counts maybe elevated in this condition, but the neutrophil percentage is usually below the threshold fordiagnosis of PJI. (See "Complications of total hip arthroplasty".)

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https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-q-fever?search=osteomyelitis&topicRef=7664&source=see_link




https://www.uptodate.com/contents/complications-of-total-hip-arthroplasty?sectionName=Aseptic+loosening&search=osteomyelitis&topicRef=7664&anchor=H3079624757&source=see_link#H3079624757

https://www.uptodate.com/contents/complications-of-total-hip-arthroplasty?sectionName=Aseptic+loosening&search=osteomyelitis&topicRef=7664&anchor=H3079624757&source=see_link#H3079624757

https://www.uptodate.com/contents/complications-of-total-hip-arthroplasty?sectionName=Dislocation&search=osteomyelitis&topicRef=7664&anchor=H344214132&source=see_link#H344214132

https://www.uptodate.com/contents/complications-of-total-hip-arthroplasty?sectionName=Dislocation&search=osteomyelitis&topicRef=7664&anchor=H344214132&source=see_link#H344214132

https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-gout?search=osteomyelitis&topicRef=7664&source=see_link

https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-calcium-pyrophosphate-crystal-deposition-cppd-disease?search=osteomyelitis&topicRef=7664&source=see_link

https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-calcium-pyrophosphate-crystal-deposition-cppd-disease?search=osteomyelitis&topicRef=7664&source=see_link

https://www.uptodate.com/contents/overview-of-hemarthrosis?search=osteomyelitis&topicRef=7664&source=see_link

https://www.uptodate.com/contents/complications-of-total-hip-arthroplasty?sectionName=Osteolysis+and+wear&search=osteomyelitis&topicRef=7664&anchor=H4246426946&source=see_link#H4246426946

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INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." TheBasics patient education pieces are written in plain language, at the 5 to 6 grade reading level, andthey answer the four or five key questions a patient might have about a given condition. These articlesare best for patients who want a general overview and who prefer short, easy-to-read materials.Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. Thesearticles are written at the 10 to 12 grade reading level and are best for patients who want in-depthinformation and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or emailthese topics to your patients. (You can also locate patient education articles on a variety of subjects bysearching on patient info and the keyword(s) of interest.)

SUMMARY

th th

th th

Beyond the Basics topic (see "Patient education: Joint infection (Beyond the Basics)")●

Prosthetic joint infection (PJI) is a serious complication of prosthetic joint implantation. The rate ofPJI is highest during the first two years following surgery. The rate of PJI ranges between 0.5 to 2percent for knee replacements, 0.5 to 1.0 percent for hip replacements, and <1 percent forshoulder replacements. The higher rate of PJI in knee arthroplasties may be attributable to greatermobility in the joint and soft tissue and less protective soft tissue coverage. (See 'Epidemiology'above.)

●

PJIs may be categorized as early onset (<3 months after surgery), delayed onset (3 to 12 monthsafter surgery), and late onset (>12 months after surgery). The timing of infection can be a clue asto the mechanism of infection and the identity of the infecting organism. However, these definitionsare controversial and not always clear-cut, particularly in patients for whom the diagnosis isdelayed. (See 'Definitions' above and 'Microbiology' above.)

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The clinical manifestations of PJI depend on the timing of symptom onset (see 'Clinicalmanifestations' above):

●

Patients with early-onset infection may present with hematoma formation or superficialnecrosis of the incision. One or more of the following findings may be observed: joint pain,warmth, erythema, induration, or edema at the incision site, wound drainage or dehiscence,joint effusion, and fever.

•

Patients with delayed-onset infection typically present with an indolent course characterized bypersistent joint pain, with or without early implant loosening. Fever is present in less than half

•

https://www.uptodate.com/contents/joint-infection-beyond-the-basics?search=osteomyelitis&topicRef=7664&source=see_link




of cases. Sinus tract associated with intermittent drainage may be observed; in the absence ofa sinus tract, physical exam findings are often minimal.

Patients with late-onset infection typically present with acute onset of systemic symptomsassociated with bacteremia, together with joint pain in a previously well-functioning joint.

•

PJI should be suspected patients with a joint prosthesis and relevant signs and symptoms ofinfection (including joint pain, warmth, erythema, induration, or edema at the incision site, sinustract or persistent wound drainage, wound dehiscence, joint effusion, or fever). The diagnosis ofPJI can be challenging because the definition is not standardized; a number of diagnostic criteriahave been proposed (table 2). (See 'Clinical approach' above.)

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The diagnosis of PJI may be established in any of the following circumstances (see 'Clinicalapproach' above):

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Presence of a sinus tract that communicates with the prosthesis•

Two or more periprosthetic cultures with phenotypically identical organisms (≥2 intraoperativecultures or a combination of preoperative synovial fluid aspiration culture and intraoperativetissue culture)

•

In the setting of suspected PJI, initial diagnostic evaluation consists of plain radiography (toevaluate for alternative causes of pain and instability) and measurement of serum inflammatorymarkers (erythrocyte sedimentation rate and C-reactive protein). Thereafter, diagnosticarthrocentesis should be performed (unless a sinus tract is present and definitive debridement isplanned). Synovial fluid should be sent for cell count with differential, Gram stain, aerobic andanaerobic culture, and crystal analysis. In patients with a sinus tract, drainage (collected byaspiration) should be sent for culture. In patients with fever or other systemic manifestations ofinfection, blood cultures (two sets) should be obtained. Intraoperative specimens should consist ofat least three periprosthetic tissue samples (ideally five); if pus is encountered, it should beaspirated in a sterile tube and sent for culture. (See 'Obtaining diagnostic studies' above.)

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For cases in which a definitive diagnosis of PJI cannot be made, additional data (including seruminflammatory markers and synovial fluid examination) may provide supportive evidence regardingthe likelihood of infection. The approach to interpretation of synovial fluid analysis depends in parton the timing of clinical presentation. The interpretation of synovial fluid parameters in the contextof other clinical factors has not been standardized; we favor the Musculoskeletal Infection Society2011 diagnostic criteria, which are used most widely (table 2). (See 'Clinical approach' above and'Synovial fluid analysis' above.)

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REFERENCES

1. Beam E, Osmon D. Prosthetic Joint Infection Update. Infect Dis Clin North Am 2018; 32:843.

2. Abad CL, Haleem A. Prosthetic Joint Infections: an Update. Curr Infect Dis Rep 2018; 20:15.

3. Gomez-Urena EO, Tande AJ, Osmon DR, Berbari EF. Diagnosis of Prosthetic Joint Infection:Cultures, Biomarker and Criteria. Infect Dis Clin North Am 2017; 31:219.

4. Parvizi J, Tan TL, Goswami K, et al. The 2018 Definition of Periprosthetic Hip and Knee Infection:An Evidence-Based and Validated Criteria. J Arthroplasty 2018; 33:1309.

5. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic jointinfection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis2013; 56:e1.

6. Parvizi J, Gehrke T, International Consensus Group on Periprosthetic Joint Infection. Definition ofperiprosthetic joint infection. J Arthroplasty 2014; 29:1331.

7. American Academy of Orthopaedic Surgeons. Diagnosis and prevention of periprosthetic joint infections clinical practice guideline. https://www.aaos.org/pjiguideline (Accessed on September 16, 2019).

8. Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic joint infection: from theWorkgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 2011; 469:2992.

9. Sloan M, Premkumar A, Sheth NP. Projected Volume of Primary Total Joint Arthroplasty in theU.S., 2014 to 2030. J Bone Joint Surg Am 2018; 100:1455.

10. Koh CK, Zeng I, Ravi S, et al. Periprosthetic Joint Infection Is the Main Cause of Failure forModern Knee Arthroplasty: An Analysis of 11,134 Knees. Clin Orthop Relat Res 2017; 475:2194.

11. Namba RS, Inacio MC, Paxton EW. Risk factors associated with deep surgical site infections afterprimary total knee arthroplasty: an analysis of 56,216 knees. J Bone Joint Surg Am 2013; 95:775.

12. Edwards JR, Peterson KD, Mu Y, et al. National Healthcare Safety Network (NHSN) report: datasummary for 2006 through 2008, issued December 2009. Am J Infect Control 2009; 37:783.

13. Wang FD, Wang YP, Chen CF, Chen HP. The incidence rate, trend and microbiological aetiologyof prosthetic joint infection after total knee arthroplasty: A 13 years' experience from a tertiarymedical center in Taiwan. J Microbiol Immunol Infect 2018; 51:717.

14. Runner RP, Mener A, Roberson JR, et al. Prosthetic Joint Infection Trends at a DedicatedOrthopaedics Specialty Hospital. Adv Orthop 2019; 2019:4629503.





























15. Lenguerrand E, Whitehouse MR, Beswick AD, et al. Risk factors associated with revision forprosthetic joint infection following knee replacement: an observational cohort study from Englandand Wales. Lancet Infect Dis 2019; 19:589.

16. Kurtz SM, Ong KL, Lau E, et al. Prosthetic joint infection risk after TKA in the Medicarepopulation. Clin Orthop Relat Res 2010; 468:52.

17. Lenguerrand E, Whitehouse MR, Beswick AD, et al. Risk factors associated with revision forprosthetic joint infection after hip replacement: a prospective observational cohort study. LancetInfect Dis 2018; 18:1004.

18. Kunutsor SK, Whitehouse MR, Blom AW, et al. Patient-Related Risk Factors for PeriprostheticJoint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. PLoS One2016; 11:e0150866.

19. Berbari EF, Osmon DR, Lahr B, et al. The Mayo prosthetic joint infection risk score: implication forsurgical site infection reporting and risk stratification. Infect Control Hosp Epidemiol 2012; 33:774.

20. Jämsen E, Nevalainen P, Eskelinen A, et al. Obesity, diabetes, and preoperative hyperglycemiaas predictors of periprosthetic joint infection: a single-center analysis of 7181 primary hip andknee replacements for osteoarthritis. J Bone Joint Surg Am 2012; 94:e101.

21. Momohara S, Kawakami K, Iwamoto T, et al. Prosthetic joint infection after total hip or kneearthroplasty in rheumatoid arthritis patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs. Mod Rheumatol 2011; 21:469.

22. Rao N, Cannella BA, Crossett LS, et al. Preoperative screening/decolonization forStaphylococcus aureus to prevent orthopedic surgical site infection: prospective cohort study with2-year follow-up. J Arthroplasty 2011; 26:1501.

23. Kong L, Cao J, Zhang Y, et al. Risk factors for periprosthetic joint infection following primary totalhip or knee arthroplasty: a meta-analysis. Int Wound J 2017; 14:529.

24. Tande AJ, Palraj BR, Osmon DR, et al. Clinical Presentation, Risk Factors, and Outcomes ofHematogenous Prosthetic Joint Infection in Patients with Staphylococcus aureus Bacteremia. AmJ Med 2016; 129:221.e11.

25. Honkanen M, Jämsen E, Karppelin M, et al. Periprosthetic Joint Infections as a Consequence ofBacteremia. Open Forum Infect Dis 2019; 6:ofz218.

26. Lewis SS, Dicks KV, Chen LF, et al. Delay in diagnosis of invasive surgical site infectionsfollowing knee arthroplasty versus hip arthroplasty. Clin Infect Dis 2015; 60:990.

27. Shah NB, Osmon DR, Fadel H, et al. Laboratory and clinical characteristics of Staphylococcus



































lugdunensis prosthetic joint infections. J Clin Microbiol 2010; 48:1600.

28. Renz N, Mudrovcic S, Perka C, Trampuz A. Orthopedic implant-associated infections caused byCutibacterium spp. - A remaining diagnostic challenge. PLoS One 2018; 13:e0202639.

29. Kanafani ZA, Sexton DJ, Pien BC, et al. Postoperative joint infections due to Propionibacteriumspecies: a case-control study. Clin Infect Dis 2009; 49:1083.

30. Mook WR, Klement MR, Green CL, et al. The Incidence of Propionibacterium acnes in OpenShoulder Surgery: A Controlled Diagnostic Study. J Bone Joint Surg Am 2015; 97:957.

31. Achermann Y, Liu J, Zbinden R, et al. Propionibacterium avidum: A Virulent Pathogen CausingHip Periprosthetic Joint Infection. Clin Infect Dis 2018; 66:54.

32. Böni L, Kuster SP, Bartik B, et al. Association of Cutibacterium avidum Colonization in the GroinWith Obesity: A Potential Risk Factor for Hip Periprosthetic Joint Infection. Clin Infect Dis 2018;67:1878.

33. Berbari EF, Marculescu C, Sia I, et al. Culture-negative prosthetic joint infection. Clin Infect Dis2007; 45:1113.

34. Malekzadeh D, Osmon DR, Lahr BD, et al. Prior use of antimicrobial therapy is a risk factor forculture-negative prosthetic joint infection. Clin Orthop Relat Res 2010; 468:2039.

35. Tande AJ, Osmon DR, Greenwood-Quaintance KE, et al. Clinical characteristics and outcomes ofprosthetic joint infection caused by small colony variant staphylococci. MBio 2014; 5:e01910.

36. Million M, Bellevegue L, Labussiere AS, et al. Culture-negative prosthetic joint arthritis related toCoxiella burnetii. Am J Med 2014; 127:786.e7.

37. Zimmerli W, Waldvogel FA, Vaudaux P, Nydegger UE. Pathogenesis of foreign body infection:description and characteristics of an animal model. J Infect Dis 1982; 146:487.

38. Zimmerli W, Lew PD, Waldvogel FA. Pathogenesis of foreign body infection. Evidence for a localgranulocyte defect. J Clin Invest 1984; 73:1191.

39. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistentinfections. Science 1999; 284:1318.

40. Donlan RM. Biofilm formation: a clinically relevant microbiological process. Clin Infect Dis 2001;33:1387.

41. Anwar H, Strap JL, Chen K, Costerton JW. Dynamic interactions of biofilms of mucoidPseudomonas aeruginosa with tobramycin and piperacillin. Antimicrob Agents Chemother 1992;36:1208.


































42. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004; 351:1645.

43. Trampuz A, Hanssen AD, Osmon DR, et al. Synovial fluid leukocyte count and differential for thediagnosis of prosthetic knee infection. Am J Med 2004; 117:556.

44. Maderazo EG, Judson S, Pasternak H. Late infections of total joint prostheses. A review andrecommendations for prevention. Clin Orthop Relat Res 1988; :131.

45. Rao JP, Bronstein R. Dislocations following arthroplasties of the hip. Incidence, prevention, andtreatment. Orthop Rev 1991; 20:261.

46. Rodríguez D, Pigrau C, Euba G, et al. Acute haematogenous prosthetic joint infection:prospective evaluation of medical and surgical management. Clin Microbiol Infect 2010; 16:1789.

47. Bereza PL, Ekiel A, Auguściak-Duma A, et al. Identification of silent prosthetic joint infection:preliminary report of a prospective controlled study. Int Orthop 2013; 37:2037.

48. Jacobs AME, Bénard M, Meis JF, et al. The unsuspected prosthetic joint infection : incidence andconsequences of positive intra-operative cultures in presumed aseptic knee and hip revisions.Bone Joint J 2017; 99-B:1482.

49. Berbari E, Mabry T, Tsaras G, et al. Inflammatory blood laboratory levels as markers of prostheticjoint infection: a systematic review and meta-analysis. J Bone Joint Surg Am 2010; 92:2102.

50. Lee YS, Koo KH, Kim HJ, et al. Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic JointInfection: A Systematic Review and Meta-Analysis. J Bone Joint Surg Am 2017; 99:2077.

51. Li R, Lu Q, Chai W, et al. Saline Solution Lavage and Reaspiration for Culture with a BloodCulture System Is a Feasible Method for Diagnosing Periprosthetic Joint Infection in Patients withInsufficient Synovial Fluid. J Bone Joint Surg Am 2019; 101:1004.

52. Wadey VM, Huddleston JI, Goodman SB, et al. Use and cost-effectiveness of intraoperative acid-fast bacilli and fungal cultures in assessing infection of joint arthroplasties. J Arthroplasty 2010;25:1231.

53. Mackowiak PA, Jones SR, Smith JW. Diagnostic value of sinus-tract cultures in chronicosteomyelitis. JAMA 1978; 239:2772.

54. Tande AJ, Patel R. Prosthetic joint infection. Clin Microbiol Rev 2014; 27:302.

55. Tsaras G, Maduka-Ezeh A, Inwards CY, et al. Utility of intraoperative frozen sectionhistopathology in the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am 2012; 94:1700.

56. Kwiecien G, George J, Klika AK, et al. Intraoperative Frozen Section Histology: Matched for




































Musculoskeletal Infection Society Criteria. J Arthroplasty 2017; 32:223.

57. Bémer P, Léger J, Tandé D, et al. How Many Samples and How Many Culture Media ToDiagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective MulticenterStudy. J Clin Microbiol 2016; 54:385.

58. Minassian AM, Newnham R, Kalimeris E, et al. Use of an automated blood culture system (BDBACTEC™) for diagnosis of prosthetic joint infections: easy and fast. BMC Infect Dis 2014;14:233.

59. Peel TN, Dylla BL, Hughes JG, et al. Improved Diagnosis of Prosthetic Joint Infection by CulturingPeriprosthetic Tissue Specimens in Blood Culture Bottles. mBio 2016; 7:e01776.

60. Saleh A, Guirguis A, Klika AK, et al. Unexpected positive intraoperative cultures in asepticrevision arthroplasty. J Arthroplasty 2014; 29:2181.

61. Qu X, Zhai Z, Wu C, et al. Preoperative aspiration culture for preoperative diagnosis of infection intotal hip or knee arthroplasty. J Clin Microbiol 2013; 51:3830.

62. Pandey R, Berendt AR, Athanasou NA. Histological and microbiological findings in non-infectedand infected revision arthroplasty tissues. The OSIRIS Collaborative Study Group. OxfordSkeletal Infection Research and Intervention Service. Arch Orthop Trauma Surg 2000; 120:570.

63. Ali F, Wilkinson JM, Cooper JR, et al. Accuracy of joint aspiration for the preoperative diagnosis ofinfection in total hip arthroplasty. J Arthroplasty 2006; 21:221.

64. Schinsky MF, Della Valle CJ, Sporer SM, Paprosky WG. Perioperative testing for joint infection inpatients undergoing revision total hip arthroplasty. J Bone Joint Surg Am 2008; 90:1869.

65. Ghanem E, Parvizi J, Burnett RS, et al. Cell count and differential of aspirated fluid in thediagnosis of infection at the site of total knee arthroplasty. J Bone Joint Surg Am 2008; 90:1637.

66. Parvizi J, Ghanem E, Sharkey P, et al. Diagnosis of infected total knee: findings of a multicenterdatabase. Clin Orthop Relat Res 2008; 466:2628.

67. Zmistowski B, Restrepo C, Huang R, et al. Periprosthetic joint infection diagnosis: a completeunderstanding of white blood cell count and differential. J Arthroplasty 2012; 27:1589.

68. Chalmers PN, Sporer SM, Levine BR. Correlation of aspiration results with periprosthetic sepsis inrevision total hip arthroplasty. J Arthroplasty 2014; 29:438.

69. Zahar A, Lausmann C, Cavalheiro C, et al. How Reliable Is the Cell Count Analysis in theDiagnosis of Prosthetic Joint Infection? J Arthroplasty 2018; 33:3257.

70. Bonanzinga T, Zahar A, Dütsch M, et al. How Reliable Is the Alpha-defensin Immunoassay Test


































for Diagnosing Periprosthetic Joint Infection? A Prospective Study. Clin Orthop Relat Res 2017;475:408.

71. Suen K, Keeka M, Ailabouni R, Tran P. Synovasure 'quick test' is not as accurate as thelaboratory-based α-defensin immunoassay: a systematic review and meta-analysis. Bone Joint J2018; 100-B:66.

72. Honsawek S, Deepaisarnsakul B, Tanavalee A, et al. Relationship of serum IL-6, C-reactiveprotein, erythrocyte sedimentation rate, and knee skin temperature after total knee arthroplasty: aprospective study. Int Orthop 2011; 35:31.

73. McArthur BA, Abdel MP, Taunton MJ, et al. Seronegative infections in hip and knee arthroplasty:periprosthetic infections with normal erythrocyte sedimentation rate and C-reactive protein level.Bone Joint J 2015; 97-B:939.

74. Tigges S, Stiles RG, Roberson JR. Appearance of septic hip prostheses on plain radiographs.AJR Am J Roentgenol 1994; 163:377.

75. Smith SL, Wastie ML, Forster I. Radionuclide bone scintigraphy in the detection of significantcomplications after total knee joint replacement. Clin Radiol 2001; 56:221.

76. Censullo A, Vijayan T. Using Nuclear Medicine Imaging Wisely in Diagnosing Infectious Diseases.Open Forum Infect Dis 2017; 4:ofx011.

77. Kwee TC, Kwee RM, Alavi A. FDG-PET for diagnosing prosthetic joint infection: systematic reviewand metaanalysis. Eur J Nucl Med Mol Imaging 2008; 35:2122.

78. Fehring TK, McAlister JA Jr. Frozen histologic section as a guide to sepsis in revision jointarthroplasty. Clin Orthop Relat Res 1994; :229.

79. Abdul-Karim FW, McGinnis MG, Kraay M, et al. Frozen section biopsy assessment for thepresence of polymorphonuclear leukocytes in patients undergoing revision of arthroplasties. ModPathol 1998; 11:427.

80. Della Valle CJ, Bogner E, Desai P, et al. Analysis of frozen sections of intraoperative specimensobtained at the time of reoperation after hip or knee resection arthroplasty for the treatment ofinfection. J Bone Joint Surg Am 1999; 81:684.

81. Musso AD, Mohanty K, Spencer-Jones R. Role of frozen section histology in diagnosis of infectionduring revision arthroplasty. Postgrad Med J 2003; 79:590.

82. Francés Borrego A, Martínez FM, Cebrian Parra JL, et al. Diagnosis of infection in hip and kneerevision surgery: intraoperative frozen section analysis. Int Orthop 2007; 31:33.

83. Ko PS, Ip D, Chow KP, et al. The role of intraoperative frozen section in decision making in





































revision hip and knee arthroplasties in a local community hospital. J Arthroplasty 2005; 20:189.

84. Schäfer P, Fink B, Sandow D, et al. Prolonged bacterial culture to identify late periprosthetic jointinfection: a promising strategy. Clin Infect Dis 2008; 47:1403.

85. Butler-Wu SM, Burns EM, Pottinger PS, et al. Optimization of periprosthetic culture for diagnosisof Propionibacterium acnes prosthetic joint infection. J Clin Microbiol 2011; 49:2490.

86. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee prostheses fordiagnosis of infection. N Engl J Med 2007; 357:654.

87. Zhai Z, Li H, Qin A, et al. Meta-analysis of sonication fluid samples from prosthetic componentsfor diagnosis of infection after total joint arthroplasty. J Clin Microbiol 2014; 52:1730.

88. Portillo ME, Salvadó M, Trampuz A, et al. Sonication versus vortexing of implants for diagnosis ofprosthetic joint infection. J Clin Microbiol 2013; 51:591.

89. Larsen LH, Khalid V, Xu Y, et al. Differential Contributions of Specimen Types, Culturing, and 16SrRNA Sequencing in Diagnosis of Prosthetic Joint Infections. J Clin Microbiol 2018; 56.

90. Bémer P, Plouzeau C, Tande D, et al. Evaluation of 16S rRNA gene PCR sensitivity andspecificity for diagnosis of prosthetic joint infection: a prospective multicenter cross-sectionalstudy. J Clin Microbiol 2014; 52:3583.

91. Sebastian S, Malhotra R, Sreenivas V, et al. Utility of 16S rRNA PCR in the Synovial Fluid for theDiagnosis of Prosthetic Joint Infection. Ann Lab Med 2018; 38:610.

92. Melendez DP, Greenwood-Quaintance KE, Berbari EF, et al. Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection. JClin Microbiol 2016; 54:120.

93. Street TL, Sanderson ND, Atkins BL, et al. Molecular Diagnosis of Orthopedic-Device-RelatedInfection Directly from Sonication Fluid by Metagenomic Sequencing. J Clin Microbiol 2017;55:2334.

94. Thoendel MJ, Jeraldo PR, Greenwood-Quaintance KE, et al. Identification of Prosthetic JointInfection Pathogens Using a Shotgun Metagenomics Approach. Clin Infect Dis 2018; 67:1333.

95. Jun Y, Jianghua L. Diagnosis of Periprosthetic Joint Infection Using Polymerase Chain Reaction:An Updated Systematic Review and Meta-Analysis. Surg Infect (Larchmt) 2018; 19:555.

96. Yan Q, Wi YM, Thoendel MJ, et al. Evaluation of the CosmosID Bioinformatics Platform forProsthetic Joint-Associated Sonicate Fluid Shotgun Metagenomic Data Analysis. J Clin Microbiol2019; 57.


































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