osteomyelitis is inflammation of the bone caused by an infecting organism

8/10/2019 Osteomyelitis is Inflammation of the Bone Caused by an Infecting Organism

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Osteomyelitis is inflammation of the bone caused by an infecting organism. Although bone isnormally resistant to bacterial colonization, events such as trauma, surgery, presence offoreign bodies, or prostheses may disrupt bony integrity and lead to the onset of boneinfection. Osteomyelitis can also result from hematogenous spread after bacteremia. When

prosthetic joints are associated with infection, microorganisms typically grow in biofilm,

which protects bacteria from antimicrobial treatment and the host immune response.

Early and specific treatment is important in osteomyelitis, and identification of the causativemicroorganisms is essential for antibiotic therapy. [ ! "he major cause of bone infections isStaphylococcus aureus . #nfections with an open fracture or associated with joint prosthesesand trauma often re$uire a combination of antimicrobial agents and surgery. When biofilmmicroorganisms are involved, as in joint prostheses, a combination of rifampicin with otherantibiotics might be necessary for treatment.

Epidemiology

Appro%imately &'( of adult cases of osteomyelitis are hematogenous, which is morecommon in males for un)nown reasons. [&!

"he incidence of spinal osteomyelitis, as depicted in the image below, was estimated to be in *+',''' in &'' . owever, the overall incidence of vertebral osteomyelitis is believed tohave increased in recent years because of intravenous drug use, increasing age of the

population, and higher rates of nosocomial infection due to intravascular devices and otherinstrumentation. [-, *!


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Osteomyelitis of " ' secondary to streptococcal disease. hotography by /avid Effron 0/,1A2E .

"he overall incidence of osteomyelitis is higher in developing countries.

Etiology

osttraumatic osteomyelitis accounts for as many as *3( of cases of osteomyelitis.

Other major causes of osteomyelitis include vascular insufficiency 4mostly occurring in persons with diabetes5 -*(6 and hematogenous seeding 4 7(6.


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0otor vehicle accidents, sports injuries, and the use of orthopedic hardware to managetrauma also contribute to the apparent increase in prevalence of posttraumatic osteomyelitis.

Osteomyelitis may complicate puncture wounds of the foot, occurring in .8(9:.*( of patients following injury. [+, :, 3, 8, 7!

Pathophysiology

;one is normally resistant to infection. owever, when microorganisms are introduced into bone hematogenously from surrounding structures or from direct inoculation related tosurgery or trauma, osteomyelitis can occur. ;one infection may result from the treatment oftrauma, which allows pathogens to enter bone and proliferate in the traumatized tissue. When

bone infection persists for months, the resulting infection is referred to as chronicosteomyelitis 4depicted in the image below6 and may be polymicrobial. Although all bonesare subject to infection, the lower e%tremity is most commonly involved. [ , '!


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osttraumatic osteomyelitis more commonly affects adults and typically occurs in the tibia."he most common isolated organism is S aureus . At the same time, local soft9tissuevascularity may be compromised, leading to interference with healing. 2ompared withhematogenous infection, posttraumatic infection begins outside the bony corte% and wor)s itsway in toward the medullary canal. =ow9grade fever, drainage, and pain may be present. =oss

of bone stability, necrosis, and soft tissue damage may lead to a greater ris) of recurrence. [&, &!


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antibiotics. "he infection usually originates hematogenously and involves & adjacentvertebrae with the corresponding intervertebral dis). "he lumbar spine is most commonlyaffected, followed by the thoracic and cervical regions. [&, !


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"arefaction and periosteal ne -bone formation around theleft upper bula in a 12-year-old patient. This as caused by subacuteosteomyelitis.

>ram9negative bacteria such as Pseudomonas species or Escherichia coli are common causesof infection after puncture wounds of the feet or open injuries to bone. Anaerobes can alsocause bone infection after human or animal bites.

Osteomyelitis in the neonate results from hematogenous spread, especially in patients withindwelling central venous catheters. "he common organisms in osteomyelitis of the neonateinclude those that fre$uently cause neonatal sepsis, namely group ; Streptococcus species,and E coli. #nfections in the neonate can involve multiple osseous sites, and appro%imatelyhalf of the cases also involve eventual development of septic arthritis in the adjacent joint.

2hildren with sic)le cell disease are at an increased ris) for bacterial infections, andosteomyelitis is the second most common infection in these patients. "he most common

organisms involved in osteomyelitis in children with sic)le cell anemia include Salmonella species, S aureus , Serratia species, and Proteus mirabilis .
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Presentation

Osteomyelitis is often diagnosed clinically with nonspecific symptoms such as fever, chills,fatigue, lethargy, or irritability. "he classic signs of inflammation, including local pain,swelling, or redness, may also occur and normally disappear within +93 days. [ !

2hronic posttraumatic osteomyelitis re$uires a detailed history for diagnosis, includinginformation regarding the initial injury and previous antibiotic and surgical treatment. Weight

bearing and function of the involved e%tremity are typically disturbed. =ocal pain, swelling,erythema, and edema may also be reported .[ '!

On physical e%amination, scars or local disturbance of wound healing may be noted alongwith the cardinal signs of inflammation. [ '! @ange of motion, deformity, and local signs of

impaired vascularity are also sought in the involved e%tremity. #f periosteal tissues areinvolved, point tenderness may be present. [ &!

#n children, the clinical presentation of osteomyelitis can be challenging for physicians because it can present with only nonspecific signs and symptoms, and the clinical findingsare e%tremely variable. 2hildren may present with decreased movement and pain in theaffected limb and adjacent joint, as well as edema and erythema over the involved area. #naddition, children may also present with fever, malaise, and irritability. ?ewborns withosteomyelitis may demonstrate decreased movement of a limb without any other signs orsymptoms.

Indications


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Laboratory Studies

Complete blood cell countA complete blood cell 42;26 count is useful for evaluating leu)ocytosis and anemia .=eu)ocytosis is common in acute osteomyelitis before therapy. "he leu)ocyte count rarelye%ceeds +,''' B= acutely and is usually normal in chronic osteomyelitis.

Erythrocyte sedimentation rate and 29reactive protein levels are usually increased. [ :, ', 3!

Culture

;lood cultures are positive in only +'( of cases of osteomyelitis. [ &!"hey should be obtained

before or at least *8 hours after antibiotic treatment. Although sinus tract cultures do not predict the presence of gram9negative organisms, they are helpful for confirming S aureus .

;one biopsy leads to a definitive diagnosis by isolation of pathogens directly from the bonelesion. [ &!;one biopsy should be performed through uninfected tissue and prior to initiation of antibiotics or more than *8 hours after discontinuation.

Imaging Studies

"adiography

2onventional radiography is the initial imaging study at presentation of acute osteomyelitis . #t is helpful to interpret current and old radiographs together.

@adiographic findings include periosteal thic)ening or elevation, as well as corticalthic)ening, sclerosis, and irregularity. Other changes include loss of trabecular architecture,osteolysis, and new bone formation. "hese changes may not be evident until +93 days inchildren and '9 * days in adults. lain films show lytic changes after at least +'(93+( ofthe bone matri% is destroyed. "herefore, negative radiographic studies do not e%clude thediagnosis of acute osteomyelitis.

ealing fractures, cancers, and benign tumors may appear similarly on plain film.


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Osteomyelitis, chronic. #mage in a /-year-old man ithdiabetes sho s chronic osteomyelitis of the calcaneum. 0ote air in the softtissues.

CT scanning

2" is useful for guiding needle biopsies in closed infections and for preoperative planning todetect osseous abnormalities, foreign bodies, or necrotic bone and soft tissue.

2" may assist in the assessment of bony integrity, cortical disruption, and soft9tissueinvolvement. #t may also reveal edema. #ntraosseous fistula and cortical defects that lead tosoft tissue sinus tracts are also demonstrated on 2".

Although 2" may play a role in diagnosis of osteomyelitis, the scatter phenomenon mayresult in significant loss of image resolution when metal is near the area of inflammation. [&, ',

&!

!"#

0@# is a very useful modality in detecting osteomyelitis and gauging the success of therapy because of high sensitivity and e%cellent spatial resolution. "he e%tent and location ofosteomyelitis is demonstrated along with pathologic changes of bone marrow and soft tissue.[&!

Osteomyelitis, chronic. T1- and T2- eighted sagittal!"#s sho bone marro edema in $1 and obliteration of the dis% space bet een$1 and $2.

0@# shows a localized marrow abnormality in osteomyelitis. " 9weighted images typicallyshow decreased signal intensity, while "&9weighted images produce increased signalintensity .[&!#ncreased intensity on "&9weighted images may indicate sinus tracts, whiche%tend from marrow and bone to s)in through soft tissue. A decreased intensity on " 9weighted images with no change on "&9weighted images may indicate surgical or

posttraumatic scarring of bone marrow.
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ltrasonography

"he presence of fluid collection adjacent to the bone without intervening soft tissue usuallysuggests osteomyelitis. Other findings on ultrasonography include elevation and thic)eningof the periosteum. [ 8, 7, &'!

0uclear medicine imaging

"hree9phase bone scan is helpful in evaluating acute osteomyelitic and doubtful dis)itis.owever, the specificity of this procedure is decreased in secondary osteomyelitis. "he bone

scan may reveal increased metabolic activity in osteomyelitis, but this finding isindistinguishable from posttraumatic injury or following surgery or cancer .[&, !

Osteomyelitis, chronic. Three-phase technetium- mdiphosphonate bone scans 3static component4 sho increased acti)ity in the heeland in the rst and second toes and in the fth tarsometatarsal 5oint.

White blood cells labeled with 77m "c9he%amethylpropylene amine o%ime 4 77m "c9 0 AO6or #n9o%imeC "his method, when used in the combination of #n9o%ime W;2 scan with 77m "c9sulfur colloid bone marrow scan, is helpful for evaluating infections of hip prostheses.#sotope accumulates in areas of increased blood flow and new bone formation in thetechnetium977m polyphosphate scan. A negative test result may indicate an impaired bloodsupply to the affected area. When red marrow is present 4ie, a%ial s)eleton and spine6, W;2scanning is less sensitive for imaging. [&, !

:3 >a citrateC >allium citrate attaches to transferrin, which then lea)s into inflamed areas fromthe bloodstream. #ncreased upta)e may occur in infection, cancer, and sterile inflammatoryconditions. erforming a technetium977m scan along with the gallium scan may helpdistinguish bone and soft tissue inflammation and show bone detail. [&, !

&9[8 1!fluoro9&9deo%y9/9glucose 4 8 191/>6 positron emission tomography 4 E"6C #n theassessment of inflammation of spinal lesions, 8 191/> E" may provide high9resolutiontomographic images and may represent an alternative to gallium. owever, comparison with2" scans or 0@# is essential. [ !

Diagnostic Procedures

Open bone biopsy with histopathologic e%amination and culture is the criterion standard forthe microbiologic diagnosis of osteomyelitis. "his procedure may not be necessary if bloodcultures are positive with consistent radiologic findings. ?eedle biopsy may also be used toobtain bone for analysis.


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When clinical suspicion is high with negative blood cultures and needle biopsy, a repeatneedle biopsy or open biopsy should be performed. A bone sample can be collected at thetime of debridement for histopathologic diagnosis in patients with compromised vasculature."o obtain accurate cultures, bone biopsy must be performed through uninvolved tissue.2ultures of the sinus tract may be useful if S aureus and Salmonella species are isolated. [& , &&!

Histologic Findings

Acute osteomyelitis presents with acute inflammatory cells, edema, vascular congestion, andsmall9vessel thrombosis. #n early disease, infection e%tends into the surrounding soft tissue,which compromises the vascular supply to the bone, as well as host response, surgery, and orantibiotic therapy.

=arge areas of dead bone may form if both the medullary and periosteal blood supplies arecompromised. ?ecrotic bone shows e%tensive resorption and inflammatory e%udates on bone

biopsy and appears whiter than living bone owing to the loss of blood supply. "hedevelopment of granulation tissue occurs at the surface of dead bone, which is bro)en down by proteolytic enzymes, including polymorphonuclear leu)ocytes, macrophages, andosteoclasts. "his occurs most rapidly at the junction of living and necrotic bone. Ase$uestrum is formed when dead cortical bone is gradually detached from living bone.

2hronic osteomyelitis presents with pathologic findings of necrotic bone, formation of new bone, and polymorphonuclear leu)ocyte e%udation, which is joined by large numbers oflymphocytes, histiocytes, and occasional plasma cells.

"he formation of new bone occurs over wee)s or months as a vascular reaction to the

infection. ?ew bone arises from the surviving fragments of periosteum, endosteum, andcorte% in the region of infection along the intact periosteal and endosteal surfaces. #t may alsooccur when periosteum forms an involucrum, which is dead bone surrounded by a sheath ofliving bone. #nvolucrum may lead to sinus tracts due to perforations that allow pus to entersurrounding soft tissues and ultimately s)in surface. A new shaft forms as the density andthic)ness of involucrum increases.

As a result of inflammatory reaction and atrophy disuse during the active period ofosteomyelitis, surviving bone in the area of infection usually becomes osteoporotic. ;onedensity increases partially from reuse as the infection subsides and e%tensive transformationof bone may occur to conform to areas of new mechanical stresses. Over time, old living

bone and newly formed bone may appear similar and might be indistinguishable, especiallyin children.

Staging

"wo classification systems are commonly used for osteomyelitis.

Waldvogel et al 4 73'6 classified bone infections based on pathogenesis and proposed theoriginal osteomyelitis staging system. "his system groups bone infections as eitherhematogenous or osteomyelitis secondary to a contiguous focus of infection. 2ontiguous9focus osteomyelitis is further classified based on the presence or absence of vascular


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insufficiency. ;oth hematogenous and contiguous focus may then be classified as either acuteor chronic. [&-!

"he staging system designed by 2ierny90ader et al 4&''-6 is more recent and morecommonly used. #t considers host immunocompetence in addition to anatomic osseous

involvement and histologic features of osteomyelitis. [&*, !

ordon classification classifies long bone osteomyelitis based on osseous defects. "he systemuses infected tibial nonunions and segmental defects. [&+!

"ype A includes tibial defects and nonunions without significant segmental loss "ype ; includes tibial defects greater than - cm with an intact fibula

"ype 2 includes tibial defects of greater than - cm in patients without an intact fibula

"he >er classification is used to address the physiology of the wound in osteomyelitis, whichis categorized as simple sinus, chronic superficial ulcer, multiple sinuses, or multiple s)in9lined sinuses. [&:, &3! ;one infection persists if appropriate wound management is notunderta)en. #t is important to cover open tibial fractures with soft tissue early in the disease to

prevent infection and ulceration.

"he Weiland classification categorizes chronic osteomyelitis as a wound with e%posed bone, positive bone culture results, and drainage for more than : months. [&8!"his system alsoconsiders soft tissue and location of affected bone. #t does not recognize chronic infection ifwound drainage lasts less than : months.


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"ype # osteomyelitis was defined as open e%posed bone without evidence of osseousinfection but with evidence of soft9tissue infection.

"ype ## osteomyelitis showed circumferential, cortical, and endosteal infection,demonstrated on radiographs as a diffuse inflammatory response, increased bonedensity, and spindle9shaped sclerotic thic)ening of the corte%. Other radiographic

findings included areas of bony resorption and often a se$uestrum with a surroundinginvolucrum.

"ype ### osteomyelitis revealed cortical and endosteal infection associated with asegmental bone defect.

"he Felly classification addresses osteomyelitis in adults as hematogenous osteomyelitis,osteomyelitis in a fracture with union, osteomyelitis in a fracture with nonunion or

postoperative osteomyelitis without fracture. "he etiology of the infection along with itsrelationship to fracture healing is emphasized using this system. [&7, &:!

Medical TherapyAntibiotic treatment should be based on the identification of pathogens from bone cultures atthe time of bone biopsy or debridement. [ , &!;one cultures are obtained first, then suspected

pathogens are covered by initiation of a parenteral antimicrobial treatment. owever,treatment may be modified once the organism is identified. arenteral and oral antibioticsmay be used alone or in combination depending on microorganism sensitivity results, patientcompliance, and infectious disease consultation.

rophylactic treatment with the bead pouch techni$ue has been suggested in open fractures to

reduce the ris) of infection, with systemic antibiotics supplemented with antibiotic beadscompared to using systemic antibiotics alone.

"raditionally, antibiotic treatment of osteomyelitis consists of a *9 to :9wee) course. [&!Animalstudies and observations show that bone revascularization after debridement ta)es about *wee)s.

Oral antibiotics that have been proven to be effective include clindamycin, rifampin,trimethoprim9sulfametho%azole, and fluoro$uinolones. 2lindamycin is given orally afterinitial intravenous treatment for 9& wee)s and has e%cellent bioavailability. #t is activeagainst most gram9positive bacteria, including staphylococci. =inezolid is active against

methicillin9resistant staphylococci and vancomycin9resistant Enterococcus . #t inhibits bacterial protein synthesis, has e%cellent bone penetration, and is administered intravenouslyor orally.

Oral $uinolones are often used in adults for gram9negative organisms. Guinolones havee%cellent oral absorption and may be used as soon as patient is able to ta)e them. @ifampinhas an optimal intercellular concentration and a good sensitivity profile for methicillin9resistant staphylococci. #t is used in combination with cell wall active antibiotics to achievesynergistic )illing and to avoid rapid emergence of resistant strains.

Empirical therapy is necessary when it is not possible to isolate organisms from the infectionsite. [ ! ospital9ac$uired infections are usually derived from methicillin9resistant


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staphylococci. #nfections contracted outside the hospital are often polymicrobial with the presence of gram9negative bacteria.

arenteral antibiotics should be administered for several wee)s, often re$uiring patients toremain in the hospital for an e%tended duration. At this time, oral therapy is indicated only in

children whose compliance is certain. #nfection may fail to improve owing to the ability of bacteria to resist antibiotics.


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"he #lizarov method involves the use of a tissue9sparing, cortical osteotomy9osteoclasistechni$ue that preserves the osteogenic elements in the limb. "o create a preliminary callusthat can be lengthened, #lizarov advocated a delay of several days before initiatingdistraction. A high9fre$uency, small9step distraction rhythm permits regeneration of good9$uality bone and less soft9tissue complications such as nerve and vessel injury. An advantage

of using this procedure is that it minimizes the prevalence of nonunion and thus further bonegrafting by producing good9$uality bone formation.

"he ris) of repeat osteotomy and osteoclasis is also decreased owing to less9prematureconsolidation of the lengthened segment. [-'! owever, #lizarov techni$ues are often nottolerated well by patients, and other options, including amputation, may be preferred.

7ound closure

"o arrest infection, it is necessary to provide ade$uate soft9tissue coverage. [&!Over small soft9tissue defects, a split9thic)ness s)in graft may be placed, whereas large soft9tissue defectsmay be covered with local muscle flaps and free vascularized muscle flaps. @otation of alocal muscle with its neurovascular supply must be possible anatomically for that procedureto be successful.

"hese flaps bring in a blood supply, which is important for host defense mechanisms, new bone regeneration, delivery of antibiotics, and healing. "hey also may be used in combinationwith antibiotics and surgical debridement of necrotic and infected tissues. "he fibula and iliaccrest are common donor sites for free flaps.

Hyperbaric o8ygen therapy

Adjunctive hyperbaric o%ygen therapy can promote collagen production, angiogenesis, andhealing in an ischemic or infected wound. [&!

Complications

"he #lizarov techni$ue is usually well tolerated by the patient, with little associated pain. Afew complications that have been reported include pin9tract infections and cellulitis, fle%ioncontractures above and below the frame, limb edema, and bone fragment rotation withmalunion. [-&!

"he most common complication in children with osteomyelitis is recurrence of boneinfection. Although adverse outcomes are common with delays in treatment, chronic infectionmay still develop in +(9 '( of patients treated appropriately. 2ommon complications inchildren younger than 8 months include bone destruction, chronic osteomyelitis, andimpaired bone growth, especially when the growth plate is affected. Although rare, e%treme

bone destruction or thinning of the corte% can lead to pathologic fractures. When centrally placed intravenous catheters are used in cases that re$uire prolonged antibiotic treatmentintravenously, catheter9associated complications can occur. owever, the use of peripherallyinserted central venous catheters has decreased this complication.

#n a study of 3,&-8 "aiwanese patients newly diagnosed with 2O0 from &''' to &''8 whowere identified on the basis of "aiwanese ?ational ealth #nsurance 4? #6 inpatient claims,


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"seng et al found chronic osteomyelitis to be associated with an increased ris) of dementia, particularly among the younger patients studied. [--!

Outcome and Prognosis

#nade$uate therapy may lead to relapsing infection and progression to chronic infection.

Osteomyelitis, chronic. #mage in a /-year-old man ithdiabetes sho s chronic osteomyelitis of the calcaneum. 0ote air in the softtissues.

;ecause of the avascularity of bone, chronic osteomyelitis is curable only with radicalresection or amputation. "hese chronic infections may recur as acute e%acerbations, whichcan be suppressed by debridement followed by parenteral and oral antimicrobial therapy.@are complications of bone infection include pathologic fractures, secondary amyloidosis,and s$uamous cell carcinoma at the sinus tract cutaneous orifice.


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. [>uideline! 2oncia E, randini ?, 0assari =, >hisellini 1, 2onsoli H, 0enichetti 1.OsteomyelitisC clinical update for practical guidelines. Nucl Med Commun . Aug&'':5&3486C:*+9:'. [0edline! .

&. 2alhoun I , 0anring 00. Adult osteomyelitis. Infect is Clin North !m . /ec&''+5 74*6C3:+98:. [0edline! .

-. ;eronius 0, ;ergman ;, Andersson @. Hertebral osteomyelitis in >Jteborg, ross ", Faim A , @egazzoni , Widmer A1. 2urrent concepts in posttraumaticosteomyelitisC a diagnostic challenge with new imaging options. " (rauma . Iun&''&5+&4:6C & '97.[0edline! .

. ?ewman =>, Waller I, alestro 2I, . Mnsuspectedosteomyelitis in diabetic foot ulcers. /iagnosis and monitoring by leu)ocyte scanningwith indium in o%y$uinoline. "!M! .


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of two hundred and two revision total hip arthroplasties. " #one "oint Surg !m . 0ay77758 4+6C:3&98-.[0edline! .

8. Abiri 00, Firpe)ar 0, Ablow @2. OsteomyelitisC detection with M, atza)is 0I, oltom . =ocal antibiotic therapy in the treatment of open

fractures and osteomyelitis. Clin 'rthop $elat $es . Oct &''*54*&36C8:97-. [0edline! .
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osteomyelitis is inflammation of the bone caused by an infecting organism

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