case report septic arthritis
TRANSCRIPT
1
CASE REPORT
SEPTIC ARTHRITIS
By : dr. Thomas Arie Satya Wardhana
dr. Heru Soetanto Kurniawan
Supervisor : Prof. Dr. dr. Putu Astawa, SpOT(K), M. Kes
SURGERY DEPARTMENT
UDAYANA UNIVERSITY
DENPASAR
2019
2
CONTENTS
Preface .......................................................................................................................... 3
Chapter I : Introduction ......................................................................................... 4
Chapter II : Case Report ......................................................................................... 5
Chapter III : Literature Review ............................................................................... 16
Chapter IV : Discussion .......................................................................................... 33
Chapter V : Conclusion ......................................................................................... 35
References ................................................................................................................... 36
3
PREFACE
The author wants to thank God for His blessing that this report can be finished. This report
is written for completion of administration in orthopedic rotation in February 2019. The author
wants to thank all orthopedic staffs especially Prof. Dr. dr. Putu Astawa, SpOT(K) for his
guidance and correction so that this report can be done.
The author realizes that this report is far from perfect and still need correction, therefore
the author apologizes for any mistakes in this report.
Denpasar, February 26th
2019
Thomas Arie Satya
Wardhana
Heru Soetanto Kurniawan
4
CHAPTER I
INTRODUCTION
Septic arthritis is defined as direct demonstration of bacteria in synovial fluid or on
positive culture of the pathogen.1 Septic arthritis is a key consideration in adults presenting with
acute mono-articular arthritis. Prompt diagnosis and management of the disease can prevent
significant short and long term complication and mortality. The acute onset of mono-articular
joint pain, erythema, heat, and immobility should alert the clinician to suspect of sepsis.2,3
Conventional symptoms such as fever, chills, and rigors are poor marker for septic arthritis as it
has low sensitivity. Diagnosis of septic arthritis can be challenging even for skilled physician in
the management of musculoskeletal disease. The patients usually present in the primary-care or
emergency-room setting. Failure to recognized and initiate appropriate antibiotic therapy within
the first 24 to 48 hours of onset can cause sub-chondral bone loss and permanent joint
dysfunction with case fatality around 11%.2,3,4,5
This frequency is raised in polyarticular disease,
with estimates as high as 50%.5 Resistance to antibiotic is becoming global problem that affect
the management of septic arthritis as well.
5
CHAPTER II
CASE REPORT
2.1 Identity
Name : I Kadek Dwija Mahadana
Gender : Male
Birth date : 22-01-2006
Age : 13 years old
MR number : 19001471
Address : Negara
Admitted : 9-01-2019
Insurance : BPJS
Ward : Angsoka 3
2.2 History Taking
Chief complaint :
Left ankle pain
Present history of illness :
The patient came to the Sanglah General Hospital emergency room referred from the Negara
General Hospital with a diagnosis of muscle sprain left cruris suspect DVT (suspected signs of
compartment syndrome), complained of pain accompanied by swelling in the left ankle since 7
days ago. Pain like being stabbed, feels constantly, feels increasingly aggravated over time, and
feels radiating to the left thigh. The initial pain was on scale of 5/10 and before entering the
hospital the pain is felt up to 9/10 scale. Pain increases when the patient walks and decreases at
rest and takes painkillers. The patient also had fever for 5 days, with the highest temperature up
to 41oC, slightly decreased when given medication, but rose again after the effect of the drug was
gone. Pain in other joints is denied. Appetite decreases slightly because the patient has fever.
Initially 2 days before starting left ankle pain, the patient was slipped on his left ankle when
getting out of the chair at a 1.5 meter high at the integrated health post with the patient's left foot
bent inward. But after that the patient can walk as usual and feel no pain. After 2 days later the
pain and swelling of the left ankle started. Patients were taken to the nearest health center, and
given painkillers, but the complaints still existed. The next day the patient was taken to a bone
setter but did not bring results.
6
Past history of illness :
The patient has never suffered a similar complaint before. A history of allergies is denied. Other
systemic diseases such as diabetes mellitus, autoimmune disease, severe trauma to the leg area
were previously denied. The patient has not had surgery. Complete immunization history on
schedule.
Family history of illness :
History of diabetes mellitus, high blood pressure, gout, autoimmune disorders in the family is
denied. No family member suffers from a similar complaint.
Socioeconomic condition of the patient :
Both patients' parents worked as middle to lower income rice farmers.
2.3 Physical Examination
Vital signs
BP : 100/60 mmHg
HR : 110 x/mnt
Temp : 38,5oC
RR : 20 x/mnt
BW : 30 kg
General state
Head : cephalhematoma (-)
Eyes : anemis (-), ikterik (-)
ENT : within normal limit
Maxillofacial : within normal limit
Thorax : Inspection : simetric, bruise (-)
Palpation : tenderness (-), crepitation (-)
Percussion : sonor simetric
Auscultation : vesikuler simetric, rhonchi -/-, wheezing -/-
Abdomen : Inspection : bruise (-), distension (-)
7
Auscultation : BS (+) normal
Percussion : tympani
Palpation : defans (-), tenderness (-)
Extremity : warm, explained in local state
Anogenital : within normal limit
Local state
Left ankle region
Look : diffuse swelling from metatarsal I-V to 1/3 distal cruris, unclear margin,
hyperemic skin color, transilumination (-)
Feel : soft swelling, warm, tenderness (+), non-pitting, unclear margin, fluctuation
(-), no inguinal lymphnode was found, pulsation a. dorsalis pedis & a. tibialis
posterior sinistra (+2), CRT <2 seconds, sensoric was normal
Move : Active ROM ankle limited due to pain
Active ROM MTP-IP 45/90
Picture 1. Clinical picture left patient’s ankle when first came to Sanglah General Hospital
2.4 Supporting examination
Radiologic
8
Picture 2. Left ankle x-ray AP/Lat Negara General Hospital (6-01-19)
Picture 3. Left ankle x-ray AP/Lat/Mortise Sanglah General Hospital (9-01-19)
9
Picture 4. Right ankle x-ray AP/Lat/Mortise Sanglah General Hospital (9-01-19)
Laboratory results (9-01-9)
Parameter Results
Hb 12,05
WBC 32,81
PLT 152,1
SGOT 39,9
SGPT 33,8
LED 88,4
CRP 457,6
BUN 12
Cr 0,84
2.5 Diagnosis
Septic arthritis left tibiotalar joint
2.6 Management
Immobilization with backslab
Debridement + arthrotomy left tibiotalar joint + left foot fasciotomy
Empirical antibiotic Cefazolin 4x1,5g intra venous (50mg/kgBW/x) while waiting on pus culture
Analgetic & antipiretic Paracetamol 4x300mg via oral
10
Picture 5. Clinical picture post backslab at emergency room Sanglah General Hospital
Surgery report
a. Date : 11-01-2019 at 21.45-23.00
b. Type : Emergency
c. Anesthesia : Regional anesthesia
d. Surgery : Debridement + arthrotomy left tibiotalar joint + left foot fasciotomy
e. Reports :
1. Patient in supine position with spinal anesthesia
2. Desinfection with povidone iodine and drapping
3. Approach from medial site at left ankle
4. Incision layer by layer, there was pus coming from left tibiotalar joint, some pus was
taken as sample for microbiology culture
5. Fasciotomy at dorsal left foot, there was pus also, some was taken for culture
6. Incision at lateral site of left ankle, there was pus, also taken for culture
7. Irigation all operation area with NaCl 0,9% 4000ml + Gentamicin 500ml
8. Situational suture of incision wound
9. Operation was over
11
Picture 6. Clinical picture durante operation (11-01-2019)
Picture 7. Clinical picture post operation (11-01-2019)
12
Picture 8. Clinical picture wound care 20-01-2019
Picture 9. Clinical picture durante 2nd
operation (23-01-2019)
13
Picture 10. Clinical picture post operation (23-01-2019)
Picture 11. Wound care 29-01-2019
14
Picture 12. Wound care 7-02-2019
Laboratory results
Parameter/
Date
9-01-
19
12-
01-19
14-01-
19
17-01-
19
20-01-
19
24-
01-19
27-01-
19
29-01-
19
7-02-
19
Hb 12,05 4,46 6,9 9,85 9,24 8,83 11,61 10,76
WBC 32,81 32,05 34,67 22,68 20,00 17,18 17,36 16,74
PLT 152,2 89,44 265,7 603,1 686,8 704,2 708,9 392,8
LED 88,4 70,1
CRP 457,65 289,67 237,41 156,92 62,03 32,34 35,53
Pro-
calcitonin
14,99
Culture
Pus culture 11-01-2019 :
Isolated bacteria Staphylococcus aureus, sensitive : Amoxicillin/Clavulanic Acid,
Ampicillin/Sulbactam, Cefalotin, Cefazolin, Azithromycin, Erythromycin, Clindamycin,
Trimethoprim/Sulfamethoxazole
Pus culture 14-01-2019 :
Isolated bacteria Staphylococcus aureus, sensitive : Amoxicillin/Clavulanic Acid,
Oxacillin, Cefazolin, Azithromycin, Ciprofloxacin, Trimethoprim/Sulfamethoxazole
Blood culture 18-01-2019 :
Isolated bacteria Staphylococcus aureus, sensitive : Amoxicillin/Clavulanic Acid,
Ampicillin/Sulbactam, Cefalotin, Gentamicin, Ciprofloxacin, Clindamycin, Vancomycin,
Tigecycline, Trimethoprim/Sulfamethoxazole
Swab wound bed culture 20-01-2019 :
Isolated bacteria Methicillin-resistant Staphylococcus aureus (MRSA), sensitive :
Gentamicin, Ciprofloxacin, Quinupristin/Dalfopristin, Linezolid, Trimethoprim/
Sulfamethoxazole
15
Blood culture 24-01-2019 :
No growth
History of antibiotic therapy
Cefazolin 4x1,5g iv (50mg/kgBW/x) from 11-01-2019 to 17-01-2019
Ampicillin Sulbactam 4x1,5g iv (50mg/kgBW/x) from 17-01-2019 to 23-01-2019
Amikasin loading dose 750mg iv (25mg/kgBW) maintenance 1x550mg iv (18mg/kgBW/x)
from 18-01-2019 to 23-01-2019
Vancomycin loading dose 900mg iv (30mg/kgBW) maintenance 3x600mg iv
(20mg/kgBW/x) from 23-01-2019 to 4-02-2019
Ciprofloxacin 3x300mg iv (10mg/kgBW/x) from 4-02-2019 to 10-02-2019
Gentamicin loading dose 210mg iv (7mg/kgBW) maintenance 1x150mg iv (5mg/kgBW/x)
from 7-02-2019 to 10-02-2019
16
CHAPTER III
LITERATURE REVIEW
3.1 Introduction
Septic arthritis is defined as direct demonstration of bacteria in synovial fluid or on
positive culture of the pathogen.1 Septic arthritis is a key consideration in adults presenting with
acute mono-articular arthritis. Prompt diagnosis and management of the disease can prevent
significant short and long term complication and mortality. The acute onset of mono-articular
joint pain, erythema, heat, and immobility should alert the clinician to suspect of sepsis.2,3
Conventional symptoms such as fever, chills, and rigors are poor marker for septic arthritis as it
has low sensitivity.
Diagnosis of septic arthritis can be challenging even for skilled physician in the
management of musculoskeletal disease. The patients usually present in the primary-care or
emergency-room setting. Failure to recognized and initiate appropriate antibiotic therapy within
the first 24 to 48 hours of onset can cause sub-chondral bone loss and permanent joint
dysfunction with case fatality around 11%.2,3,4,5
This frequency is raised in polyarticular disease,
with estimates as high as 50%.5 Resistance to antibiotic is becoming global problem that affect
the management of septic arthritis as well.
3.2 Epidemiology & Risk Factors
Any infection, crystal-induced disease, osteoarthritis, trauma, and a variety of systemic
disease can create a painful swollen peripheral joint.6 Septic arthritis is relatively rare in the
general population (annual incidence of 2 – 10 per 100000). The obvious risk of septic arthritis
associated with age older than 60 years and recent bacteremia. Comorbidities including
rheumatoid arthritis, HIV, diabetes mellitus, leukemia, cirrhosis, cancer, granulomatous disease,
intravenous substance abuse, and renal disease greatly increase risk of developing the
infection.5,6,7,8,16
Patients with rheumatoid arthritis have an approximately 10-fold higher
incidence of septic than does the general population.10
Every bacterial organism basically has
been reported to cause septic arthritis.8,9
The most common ethiological agent of all septic arthritis cases in Europe and all non-
gonococcal cases in the US is Staphylococcus aureus.10,11,12,13,14,15
The incidence of bacterial
arthritis has been reported ranged between 5,7 to 9 per 100000 person-years in Scandinavia and
Australia with increased incidence in patients with rheumatoid arthritis and joint
prostheses.5,6,16,17
The bacteria is more common among patients with rheumatoid arthritis and
diabetes.6,10 Streptococcus spp. are the next most commonly isolated bacteria from adult
patients with septic arthritis. 1,6,51
The features of Streptococcal arthritis differ from those of S.
aureus arthritis and vary across groups.9 Streptococcus pneumoniae and Streptococcus pyogenes
are among the most common Streptococcus isolate found from synovial fluid aspiration in
17
Streptococcus arthritis.10
The most common gram-negative organism etiology are Pseudomonas
aureginosa and Eschericia coli. Anaerobes bacteria are also reported in a small percentage of
cases usually in diabetic and patients with prosthetic joints. Approximately 10% patients with
non-gonococcal arthritis have poly-microbial infections.10
Historically, Haemophilus influenza,
S. aureus, and group A Streptococci were the most common cause of infectious arthritis in
children younger than 2 years. Report in Luxembourg the good coverage of Hib vaccine given to
children cause the overall incidence of Haemophilus influenza bacterial arthritis in young
population under 2 years old is decreasing.20,23
In a recent study by Yagupsku et al, found that
nearly half of the clinical isolates from patients younger than 2 years with acute septic arthritis
were K. kingae.10,21
In conclusion, the most common causative organism in infants younger than
2 months of age are S. aureus, Streptococcus agalactiae and gam negative enteric bacteria. While
in children between the ages of 2 months and 5 years, the predominant agents include S. aureus,
S. pyogenes, S. pneumonia, and K. Kingae. And finally for children older than 5 years, the
common organism are S. aureus, and S. pyogenes.37
Gonococcal arthritis is the infection of joint caused by the diplococcal gram-negative
bacterial species Neisseria gonorrhea. It is the most common strain of infectious arthritis in US,
though it is relatively rare in western Europe.6,10,19,22,23
It creates less morbidity and has different
clinical presentation. Women are more prone to be affected by gonococcal arthritis 2 to 3 times
more frequently than men.6,18
The number of cases of gonorrhea decreased by 72% between
1975 and 2017 with a total 555.608 cases of gonorrhea were reported to CDC in 2017.24
The
decrease was correlated with a reduction in disseminated gonococcal infection and arthritis.10,24
Due to the good response to the therapy, this type of infectious arthritis is much less destructive
than non-gonococcal arthritis.19
To be noted antimicrobial resistance remains an important
consideration in the treatment of gonorrhea.24
It is important to distinguish promptly non-gonococcal septic arthritis from other causes
septic arthritis as it can cause fatal consequences as septic arthritis can destroy the cartilage of
affected joint within days.6
18
Table 1. Common causes of infection arthritis in different patient populations.18
(Reproduced
from Sack K. Monoarthritis: differential diagnosis. Am J Med. 1997;102(suppl. 1A):30S-34S.)
Table 2. Main causative organism involved in each age (Reproduced from Gutierrez K. Bone
and joint infections in children. Pediatric Clinics of North America 2005;52:779–94.)
3.3 Definition
Case definition of septic arthritis is defined by Newman at 1976:7
1. Isolation of a pathogenic organism from an affected joint
2. Isolation of a pathogenic organism from another source (e.g. blood) in the context of a
hot red joint suspicious of sepsis
3. Typical clinical features and turbid joint fluid in the presence of previous antibiotic
treatment; and
4. Postmortem or pathological features suspicious of septic arthritis.
Morgan et al define the probable septic arthritis as patient with disease clinically consistent with
septic arthritis and:17
1. Synovial fluid leucocyte count ≥ 50000/mm3 and no other cause of arthritis identified,
but no organism identified on aspirate Gram stain or culture, OR
2. Blood culture positive but the joint not aspirated and no other cause of bacteremia
evident, OR
3. Pathogenic organism cultured from either a discharging wound sinus or in the case of N.
gonorrheae, a genito-urinary swab
3.4 Pathogenesis
The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of
the host immune response and the invading bacteria. The understanding of bacteria colonization,
infection, and induction of the host inflammatory response can gain a good understanding of the
disease. There are differences between non-gonococcal arthritis and gonococcal arthritis.
19
There are many main routes by which pathogens accumulate in the joints including:
hematogenously through synovial capillaries, infected contiguous foci, neighboring soft tissue
sepsis, or by direct penetration / insult due to trauma or iatrogenic injury / events such as
diagnostic or therapeutic arthrocentesis or joint surgery.1
There are steps that are typical before the joint can be infected and destroyed. Joint
colonization and bacteria adherence, Joint infection and the host immune response, joint damage,
bacterial by-products and their pathogenic role, and at the end bacterial clearance and joint
damage.10
Gonococcal arthritis occurs in approximately 42 to 85% with disseminated gonococcal
infection (DGI) and begin with a localized mucosal infection.10
DGI-producing strain are
unusually sensitive to in vitro killing by Penicillin G and posses unique nutritional requirement
for arginine, hypoxanthine, and uracil. The bacteria have a numbers of virulent factors. This
factors are the important component to allow the localized infection to become DGI.10
Figure 1. Pathogenesis of Staphylococcal septic arthritis (Reproduced from Mathews CJ,
Weston VC, Jones A, Field M, Coakley G. Bacterial septic arthritis in adults. Lancet.
2010;375(9717):846-855.)
Joint colonization and bacterial adherence
The synovial membrane has no basement plate under the well-vascularized synovial. More
over, the bony metaphysis of children younger than 18 months are vascularized by transphysis
vessels. And as the vessels enter the epiphysis and ultimately the joint space, young children are
believed to have a higher risk of joint space infection complicating osteomyelitis.10,37
As there is
no good wall / plate, the bacteria can easily enter the joint hematogenously. Bacteria may also
enter into the joint space by direct invasion from an infection site. Once it entered, the bacteria
then adhering and colonizing the whole joint space easily especially when there is recent injury.
20
The extracellular matrix proteins that aid in joint healing (that are formed after injury) may
promote bacterial attachment and progression to infection. The virulence and tropism especially
in Indonesia and other tropical countries of the microorganism, combined with the strength /
response of synovial to bacteria invasion are major determinants of bacterial arthritis.10
The intra
articular virulence of bacteria are varies. S. aureus organism in the knee joint of rabbit can cause
major destruction but N. gonorrheae or S. epidemidis cause no harmful joint inflammation.25
Vaccination with a recombinant fragment of the S. aureus collagen adhesin was able to
reduce the sepsis-induced mortality rate to 13%, compared with 87% in the control group in
patients with bacterial arthritis.27
Evidences supports the importance of staphylococcal surface
component as virulence determinants that enabling initial colonization. S. aureus has a variety
microbial surface component receptor that can recognize adhesive matrix molecules of host
protein that mediate adherence to the joint extra-cellular matrix or implanted medical device.29
Study by Hermann et al imply an important role for two major plasma proteins, namely
fibronectin and fibrinogen, and a minor role for laminin in staphylococcal adherence to joint
extracellular matrix or implanted medical device and thus in mediating the early steps of
bacterial colonization. 29
Elastin, collager, and hyaluronic acid are also include in the host matrix protein that are
also crucial in the adherence of bacteria. 10 The role of collagen adhesion of S. aureus as a
major virulence factor has been questioned recently due to the finding on 30 to 60% clinical
isolates do not display collagen binding in vitro or the cna-encoded collagen adhesion.27
Staphylococcal fibronectin binding proteins may also play a major role in the colonization and
virulence of septic arthritis.30
Following the colonization and internalization, staphylococci can
induce apoptosis and survive intracellularly.31,32
Induced apoptosis may exacerbate the host cell damage seen in septic arthritis.31,32
Staphylococci can escape attack by the immune system and antibiotic by remain in the host
cells.31,32
This was proven in vivo when the the S. Aureus cells were found remain in the
cytoplasm of embryonic chicken osteoblasts and osteocytes in the mineralized bone
matrix.31,32,33,34
Joint infection and host immune response
Once inside and succeeding in colonizing, bacteria then rapidly proliferate and it activates
an acute inflammatory response.1,10
Initially, cytokines (Interleukin 1-B (IL-1B) and Interleukin
6 (IL-6)) are released into the joint fluid by synovial cells.35
The cytokines activates acute-phase
protein (C-reactive protein) from liver that bind to the bacterial cell and then promote
opsonization and activate the complement system. Influx of inflammatory cell into synovia
membrane is also occurred. Then the phagocytosis by macrophages, synoviocytes, and
polymorphonuclear cells occur and is associated with the release other inflammatory cytokines
(Tumor Necrosis Factor-α, IL-8, and granulocyte-macrophage colony-stimulating factor) to
reinforce the already IL-6 and IL-1β by triggering further chemotaxis, increase expression of
adhesion molecules on endothelial cells, and enhance adhesion of circulating S. aureus to
endothelial cells.38,39,40,41,42
These cytokines and associated immune response is required for bacterial clearance and the
prevention of mortality due to bacteremia and septic shock.36,38
Nitric Oxide, a common
mediator of inflammatory cytokines, is also required. Once in the inflammatory site, phagocytes
21
are able to secrete series of products that can be harmful to the host, leading to severe tissue
damage, with pannus formation as well as cartilage and bone destruction.38 The T-cell mediated
(Th1) and humoral (Th2) adaptive immune response may also play a role in the clearance and/or
pathogenesis of acute septic arthritis The T cell can be found in the joint within a few days
following infection.38
Bacterial products and their pathogenic role
During acute septic arthritis, the innate immune system responds to the presence of the
peptidoglycan wall of S. aureus to produce pro-inflammatory cytokines (e,g, IL-1B, IL-6, and
TNF-α) and C-reactive protein. Bacterial DNA also promote an intense inflammatory response
very quickly and can last up to 14 days.43,44
It has been noted that bacterial super antigens such
as staphylococcal TSST-1 and enterotoxin may play a major role in the activation of the host
inflammatory response that can increase the mortality rates and exacerbating host inflammatory-
cell invasion, cytokine further release, and joint degradation.45
Super-antigens act by binding to
the conserved lateral regions of the host major histocompatibility complex class II molecule and
T-cell receptor. These activated T cells are then able to increase the release of number cytokines
IL-2, IFN-γ, and TNF-α that cause significant systemic toxicity and suppression of the adaptive
immune response and inhibits plasma cell differentiation as well.46
The high T-cell activation
eventually results in apoptosis and a weakened immune system, enabling the pathogen to
effectively produce a sustained and destructive infection.10
Surface associated proteins of S. aureus were reported to directly cause osteolysis in vitro
and induce cells within the bone microenvironment to release several bone-resorbing including
TNF. Strangely, TNF-α has been reported to induce the proliferation of osteoblast in vitro and
help form bone matrix as well.47
Endotoxin-LPS has also been reported to inhibit bone collagen
and non-collagenous protein synthesis.48
As mentioned before, S. aureus can survive intra-
cellularly after internalization. Type 5 capsules production by S. aureus was shown to be up-
regulated. It shows that the capsule may not only resist phagocytosis and opsonization but may
also contribute to intracellular survival.49
Some strains of S. aureus are positive for the virulence
factor Panton-Valentine leucocidin (PVL) cytotoxin, which enables the bacteria to survive in
neutrophils.3 The strain have been associated with severe fulminant infection in previously
healthy patients in USA.3,6,50
Differences regarding mortality and severity between
staphylococcal strains producing different exotoxins may be dependent on the degree of
activation of the immune system.45
Bacterial clearance versus joint damage
It is important to understand that there is subtle balance between immune response to
eliminate invading bacteria from the host and the over-activation of this response that cause the
majority of infection related joint destruction.
3.5 Diagnosis
Non-gonococcal arthritis
The classical presentation of acute non gonococcal septic arthritis includes recent onset of
fever > 39 C (34%-57% sensitivity), 1-2 weeks history of malaise (27% sensitivity), rigor (6%),
22
and local finding of tenderness, warmth, swelling, and decreased range of motion in the involved
joint.1,2,3,6,10
A significant number of patients have mild fever and may not demonstrated
localized heat, tenderness and erythema around the affected joint.1 Septic arthritis is usually
mono-articular (80%-90%).53,54,55
However, the possibility of poly-articular septic arthritis (up to
20%) should be carefully considered, especially when the patient are afebrile of have history of
poly-articular disease and or co-morbids.1,2,3,10
Atypical joint infection, including
sternoclavicular, costochondral, and sacroiliac joints, may be common in intravenous drug
users.10
Penetrating trauma or penetrating diagnostic test including human bite or animal bite as
well as local corticosteroid therapy may cause septic arthritis in atypical joints.10
Septic arthritis
in neonates and infants is more deceptive and devastating. The diagnosis often missed due to
absence of classical signs of infection. The common clinical signs include vague complains such
as irritability, anxiety, failure to thrive, tachycardia, and anemia. The hip joint is the most
frequently affected.17
To be noted that in acute joint disease, septic arthritis must be highly
suspected. While any joint can become infected, the most commonly involved joint in non-
gonococcal arthritis are the knee and hip, followed by shoulder and ankle.
Table 3. Distribution of infected joint compiled by Barton et al (reproduced from Barton, L. L.,
L. M. Dunkle, and F. H. Habib. 1987. Septic arthritis in childhood. A 13-year review. Am. J.
Dis. Child. 141:898–900)
Blood and Synovial Fluid (SF) should always be cultured promptly before starting
antibiotic treatment to boost the chances of obtaining causative organism.10
Peripheral blood
leucocyte counts are usually elevated in children but are often within normal limit in adults. C-
reactive protein level and erythrocyte sedimentation rates are elevated. Synovial fluid analysis
typically shows turbid, low-viscosity fluid with leukocyte count in excess of 50.000/mm3.
Interestingly, while nonbacterial inflammatory processes in joint may have counts way above
50.000/mm3, gonococcal and granulomatous arthritis may have counts below 50.000/mm
3.10
Krey and Bailen found that the leukocyte count of SF was greater than 50.000 cell/L in 70% of
patient with septic arthritis, 13% with gout, 10 % with pseudo-gout, and 4% with RA.56,57
To be
noted, in non-gonococcal arthritis, the fraction of Polymorphonuclear (PMN) leucocyte close to
90%.56
Shmerling concluded depressed Synovial Fluid (SF) glucose was generally not due to
traumatic arthritis and that in infectious arthritis the SF glucose can be used to monitor disease
progression.56
He also found that SF leucocyte, %PMN, and LDH were found to be most
accurate in correctly classifying patients with joint effusion.56
Whereas the SF leucocyte and SF
%PMN were elevated in inflammatory disease and normal in non inflammatory disease.56
23
Synovial fluid protein level was considered abnormal if above 25 g/L, with moderate
inflammation present if above 45 g/L.56
Table 4. Test Results (or cut-off) considered consistent with each disease category presented
(reproduced from Shmerling, R. H., T. L. Delbanco, A. N. Tosteson, and D. E. Trentham. 1990.
Synovial fluid tests. What should be ordered? JAMA 264:1009–1014)
Table 5. Synovial Fluid Analysis (reproduced from Horowitz DL, Katzap E, Horowitz, S., et al.
Approach to Septic Arthritis. Am Fam Physician. 2011;84(6):653-660.)
Imaging studies of septic arthritis are usually not revealing in the first few days of infection
as they are usually normal or show only pre-existing joint disease. However, swelling capsule
and soft tissue around the affected joint, fat pad displacement, and in some assess joint space
widening due to localized edema and effusion may be found.10
The initial radiographic image is
useful to determined associated conditions or pre-existing joint disease mentioned before. In the
late stage the radiography image can show diffuse joint space narrowing due to cartilage
destruction. It can also evaluate late, inadequately treated stages of septic arthritis, joint fusion
destruction, osteomyelitis, osteoarthritis, joint fusion, calcifications in the periarticular tissues, or
sub-chondral bone loss followed by reactive sclerosis.10
24
USG can detect early fluid effusion even in small volume of joint fluid (up to 1-2 ml),
moreover can be used as a guide for initial joint aspiration and drainage procedure.58,59
Non-
echo-free effusion (due to clotted hemorrhagic collections) are a very characteristic of a septic
joint. It is suggested that the presence of only an echo-free effusion caused by transient synovitis
and fresh hemorrhagic effusions) may rule out the diagnosis of septic arthritis.59
USG can also
evaluate the status of intra-articular compartment, joint capsule, bony surface, and adjacent soft
tissues and the response to therapy.10
CT Scan and MRI and radionuclide scan may be performed
though it is rarely needed for diagnosis of septic arthritis. The mentioned exam is used only for
ambiguous cases or to determined the extent of infections. They also useful in aiding the
diagnosis of joint infections that are difficult to access, such as sacroiliitis.60
The spatial
resolution of MRI makes it useful in differentiating infection of the bone or soft tissue. The main
disadvantage of MRI is its high cost and lack of universal availability, and low resolution of
calcified bone structure and its cortex.61
Radionuclide Bone Scan (99Tc methyldiphosponate /
99TcMDP) can shows increases isotope accumulation due to osteoblast activity and increased
vascularity. It often able to detect localized inflammation areas. It can also distinguish between
bone, joint, and soft tissue inflammation.62
Gallium and indium scan show increased isotope
uptake in the area with high concentration of PMN, macrophages, and malignant tumors.63
They
are also having higher sensitivity and specificity in detecting infection than 99mTc
methyldiphosponate.62,63
Bittini et al concluded that early demonstration and localization of the
disease / infection by 99Tc MDP Bone Scan, together with the rapid bacteriologic diagnosis,
allows for an early and more appropriate antibiotic treatment and better results.62
Figure 2. MRI of staphylococcal septic arthritis of left hip, with fluid collection between planes
of gluteal muscles (Reproduced from Mathews CJ, Weston VC, Jones A, Field M, Coakley G.
Bacterial septic arthritis in adults. Lancet. 2010;375(9717):846-855)
25
Table 5. Principles of diagnostic and management of acute nongonococcal septic arthritis
(reproduced from Shirtliff MA., Mader JT. Acute Septic Arthritis Clinical Microbiology
Reviews 2002; 15(4):527-544. doi: 10.1128/CMR.15.4.527–544.2002)
Gonoccocal Arthritis
Gonoccocal arthritis is the most common form of infectious arthritis caused by
disseminated gonococcal infection seen in both community and the major teaching hospital
(40%-52%).26
The clinical spectrum of infectious caused by Neisseria gonorrheae extends from
minor mucosal symptom to a disseminated blood-borne infection involving skin, joints,
meninges, heart, and bone. Host defenses usually able to isolate and clear the bacteria from the
system (keep it in the mucosal surface), but due to certain factor such as surface membrane of
virulence gonorrhea, antibiotic resistance, ability to resist killing by normal human serum, the
disseminated gonococcal infection sometimes occur.26
The classic skin lesion manifests as small erythematous papules which progress to
vesicular or pustular lesions and are often limited to the extremities and the trunk. If the papules
are present on the affected joint, there are typically 5 to 10 lesions. The tenosynovitis is
characterized by pain, swelling, and peri-articular erythema.
To be noted, some patients develop septic gonococcal arthritis without previous
polyarthralgia, tenosynovitis, or dermatitis. The tenosynovitis characterized by pain, swelling,
and peri-articular erythema tenosynovitis.10
There are only 21% of patients with confirmed
26
suppurative arthritis have such clinical sign.10,19
The most often affected in gonococcal arthritis
including the fingers, wrists, elbows, knees, and ankles.10
Peripheral leukocytosis and elevated erythrocyte sedimentation rates are positive in more
than half of the patients. Interestingly, N. gonorrheae is found in only about 50% synovial fluid
of patients with gonococcal arthritis. The gram stain examination has low reliability in diagnosis
gonococcal arthritis. One of the best tool to confirm the presence N. gonorrheae from the
negative SF culture is PCR amplication.64
It has high sensitivity and specificity (96,4% & 78,6%
respectively), with false-positive rate at 3.6%.64
To be noted that the use of PCR based method
should not replace the “gold standard” of SF culture.10
Table 6. Clinical criteria for culture-negative gonococcal arthritis (reproduced from Liebling, M.
R., D. G. Arkfeld, G. A. Michelini, M. J. Nishio, B. J. Eng, T. Jin, and J. S. Louie. 1994.
Identification of Neisseria gonorrhoeae in synovial fluid using the polymerase chain reaction.
Arthritis Rheum. 37:702–709)
Table 7. Characteristics of gonococcal and non-gonococcal bacterial arthritis (reproduced from
Goldenberg DL. Septic arthritis. Lancet. 1998;351(9097):197-202)
27
Figure 2. Algorithm for evaluating hot, swollen joint (reproduced from Goldenberg DL. Septic
arthritis. Lancet. 1998;351(9097):197-202.
3.6 Differential Diagnosis
The differential diagnosis of the septic arthritis is similar with bacterial arthritis /
rheumatoid arthritis.
Other rheumatic disorder
Gout and pseudo-gout (calcium pyrophosphate dehydrate deposition disease) are two
important form of non bacterial acute arthritis that mimic bacterial arthritis.65
Like described
before, septic arthritis is most likely among patient with recurrent / long standing rheumatoid
arthritis. An inflammatory response to extra articular presence of microorganism may be defined
as reactive arthritis.10
Most cases are associated with patients with the major histocompability
complex antigen HLA-B27. In non infectious, of course antibiotic will not effective, especially
when given at later stages of reactive arthritis.
Infectious arthritis
During past decade mycobacterial and fungal arthritis have re-emerged, partly related to
the HIV infection. 80% of joint infection in England and Wales were due to mycobacteria. The
two infection both present with the slow onset of a chronic monoarthritis. The systemic symptom
usually non systemic. At the time of diagnosis, plain radiograph demonstrates joint space
narrowing and bone erosion.4 Lyme disease may present with chronic monoarthritis mostly on
the knee joint.4 Earlier cardinal symptom include the typical erythema migrant skin lesion and
transient poly-arthralgia with viral-like features, including fever, headaches, and neurological
28
sign.4 The patient with chronic monoarthritis should be carefully considered especially with
diagnosis of mycobacterial or fungal arthritis.10
A culture synovial biopsy should be done for
fungi and acid-fast organisms in person with a chronic mono-articular involvement with negative
SF culture.66,67
Viral arthritis usually present with polyarthritis, fever, lymphadenopathy, and
rash.4
Arthritis caused by N. meningitides is almost indistinguishable from DGI, especially with
regard to the musculoskeletal manifestations and arthritis-dermatitis syndrome. Skin lesion
almost similar to the one caused by gonococcal arthritis, also can similar with the one caused by
H. influenza, Streptococcus monoliformis, and Streptococcus pyogenes.
Table 6. Differential diagnosis of bacterial arthritis (reproduced from Goldenberg DL. Septic
arthritis. Lancet. 1998;351(9097):197-202)
3.7 Management
Non-gonococcal arthritis
Acute non-gonococcal arthritis is an emergency that can cause significant even fatal
morbidity and mortality. Aggressive and rapid treatment is essential to prevent any harmful
effect from the disease. Most people with suppurative arthritis respond clinically to appropriate
antimicrobial agents after initial diagnostic aspiration of SF. Therefore, the initial antibiotic
given should be a broad spectrum based on the gram’s stain and the age and the risk factors of
29
the patients, and should be given as soon as possible after collection of SF. It is given based on
empiric therapy that are confirmed from clinical presentation and clinical course, physical
examination, and analysis and culture of SF. When the gram’s stain is found negative, empirical
therapy would be given that should cover S. aureus and Streptococci.67
The history and clinical course can provide clues and information that can distinguish the
cause of arthritis such as gonococcal, non gonococcal, or granulomatous. The usual course of
therapy for non gonococcal arthritis is 2 weeks for arthritis due to H. influenzae or Streptococcus
spp. And 3 weeks for arthritis due to S. aureus or gram – negative bacilli.10
Initial antibiotic
therapies in children younger than 5 years includes Cefuroxime, Cefotaxime, or Ceftriaxone
depending on the result of culture of joint and blood.10
Initial therapy for patients older than 5
years is aided by the Gram stain. In a study of 123 children with haematogenous septic arthritis,
Odio et al concluded that management with 4 days of low dose dexamethasone combined with
antibiotic achieved better results than treatment with antibiotic alone in dealing with
Staphylococcus aureus.3,73
Similar study has been done at the adult population, and it suggest that the combination
therapy might be beneficial in all age group.74
Ceftriaxone is can be used in sexually active
adults. If S. aureus are suggestive from the culture of SF, treatment with intravenous (i.v.)
penicillinaseresistant penicillin should be considered, while if Streptococcus spp are seen,
penicillin G is used for therapy. There are other potential therapies that use interleukin 10 or
interleukin 12 in combination with antibiotics. It has been investigated in animal experimental
models.75,76
In animal experimental models the combination of biphosponates with intra-
peritoneal corticosteroid and antibiotics can result in decreased osteoclast activity and cause
reduction in skeletal destruction.77
There is no set of universally accepted criteria for choosing the drainage method. The
drainage method used should be customized to each clinical states of each patient. However,
there is general guidelines that should be followed. Patient should be initially treated with needle
joint aspiration if the infection is easily accessible, if the majority if the purulent fluid can be
removed, and if the patient doesn’t have negative prognostic indicator. The majority of the study
concluded that wrist, elbow, ankle, knee initially should be treated with needle aspiration, and
axial joints including hip, shoulder, and sterno-clavicular joint should undergo open surgical
drainage.69,70
Repeated needle aspiration for recurrent joint effusion has been used with success
during the first 7 days of treatment.69
The volume of synovial fluid, cell count, and the
percentage of PMN decrease with each aspiration, then the combination of antimicrobial therapy
and aspiration as needed may be adequate.53
However in cases of persistent effusion beyond 7
days, the arthroscopy or surgical drainage should be performed. The tidal irrigation can be as
effective as arthroscopy and can be performed at the bedside. The arthroscopy lavage has been
increasingly used in the treatment of septic arthritis of the knee.10
Arthroscopy is a less invasive technique than open surgery and provides much better
irrigation and visualization than needle aspiration.71
However, aspiration under radiologic
imaging or open surgical drainage with vigorous exploration and debridement is recommended
for hip infection as well as for joint infections possessing adhesions or loculated area of
30
abscess.10,69,72
Arthrotomy should be considered when the infected joint need to be decompressed
urgently due to neuropathy or compromised vascular system or when the infected joint is
inaccessible by less invasive method (e.g., hip, shoulder), or when the joint is already damaged,
or there is osteomyelitis. It is performed sometimes to overcome the low oxygen tension and to
neutralized the pH of the infected joint environment.10
Patient has to rest and optimal anatomical joint position has to be positioned to prevent any
deformation and contractures. Splint should be considered to maintain proper joint position (e.g.,
hip in neutral rotation with some abduction, knee in extension fully, elbow in 90 degree flexion,
and forearm in neutral rotation). The isotonic exercise is helpful in preventing atrophy. Early
physical therapy and aggressive mobilization are important part for optimal recovery and
prevention of complication such as contracture and pain.
Table 7. Initial choice of antibiotics for therapy of infectious arthritis (adult) (reproduced from
Shirtliff MA., Mader JT. Acute Septic Arthritis Clinical Microbiology Reviews 2002; 15(4):527-
544. doi: 10.1128/CMR.15.4.527–544.2002)
31
Gonococcal arthritis
The initial management of gonococcal arthritis was based on 10-million-unit intravenous
penicillin G per day, but high resistance rate of penicillin changes the protocol and
recommendation for the treatment of DGI with third generation Cephalosporin.80,81
The
resistance of penicillin is believe mediated by the acquisition of plasmids that encode Blactamase
or chromosomal mutation.78
The recommended treatment like mentioned previously, is based on
a third-generation Cephalosporin, such as Ceftriaxone (1 gr i.m or i.v.), Ceftriaxone (1 gr i.m. or
i.v. every 8 h) and Cefotaxime (1 gr i.v. every 8 h).80
Intravenous treatment should be continued
for 24-48 h until symptoms improved and resolved and then oral therapy (Ciprofloxacine 500 mg
p.o. every 12 h, Ofloxacin 400 mg p.o. every 12 h, Cefixime 400 mg p.o. every 12 h, or
cepodoxime (400 mg p.o. every 12 h)) should be initiate for 7 -10 days completion antimicrobial
therapy can be administered for oral anti microbial therapy. Skin lesions may continue to
develop for up to 2 days following the start of antibiotic.10
Sample for SF culture should be retrieved from all previously infected site to ensure the
gonococcal infection site is resolved.79
Surgical management of the affected joint is usually not
necessary, with the exception of the initial joint aspiration for synovial fluid sample collection at
presentation as the disease often rapidly resolve so sub-sequent joint drainage is often
unnecessary. However, if it is persist, it require repeated drainage as needed.
3.8 Prosthetic Joint Infection
The infection rate of hip and knee replacement is ranged from 0.5% to 2% (0.86% to 1.1%
of knee arthroplasties and 0.3% to 1.7% of hip arthroplasties), while in patients with rheumatoid
arthritis it climbs to 4.4%.4,82,84,85
Early onset of post operative infection (less than 3 months) is
highly suggestive due to surgical wound contamination and most often caused by
Staphylococcus epidermidis (coagulase-negative staphylococci).4,10,84,86
While, late infection is
usually caused by haematogenous seeding with S. aureus is the most common cause, followed by
Streptococcus spp., gram-negative bacilli, and anaerobic bacteria.4,10
The main problem regarding the complication of implants is their propensity to be coated
by host proteins (fibrinogen and fibronectin) right after implantation procedure. The bacteria that
attach to the prosthetic material through fibrinogen and fibrin binding receptor on the surface of
implant, elaborate an exoplysaccharides, a glycocalyx. The bacteria then are protected against
host phagocytes in the formed biofilm. It causes the difficulty in eradicating the infection unless
the prosthesis is removed. The implants often cause the reduce of blood flow and local
immunocompromised by impairing natural killer, lymphocytic, and phagocytic cell activities. It
also decreases the superoxide level (mediator responsible in bacterial killing in the professional
phagocytic blood cells).83
The resulting release of reactive products of oxygen and lysosomal
enzymes may cause accidental host tissue damage and local vascular compromise that can
precipitating the development of osteomyelitis. The energy that would be used for fight
infection, can be drained to supply the increasing normal phagocytic process that dedicated to
remove the implant material.
32
A two-stages procedure that consist of debridement and removal continued by
reimplantation is recommended. The principle of the management should focus on the general
stated of the patient instead of specific organism when try to assess the interval between stages
and recurrence. Earlier attempts of arthrodesis rather than repeated attempts at reimplantation are
recommended.10,85
When the patient refuse, the patient can be given suppressive oral antibiotic
therapy, but prosthesis removal still have to be performed. It is also continued with 4- to 6-weeks
course of culture directed antibiotic. Recurrence rates is up to 60% in patients with rheumatoid
arthritis.10
3.9 Prognosis
Before antibiotic era, 2/3 patients died from septic arthritis.2 Current mortality rates of
bacterial arthritis is ranged from 10 to 20 percent, depending on the presence of comorbid
disease. Factor that contribute to the mortality rate are age coexisting renal or cardiac disease and
concurrent immunosuppression.2 Adult with pneumococcal septic arthritis who survive infection
will able to return to 95% of their baseline joint after complication antibiotic therapy. Delay
diagnosis can lead to longer time being taken to clear the joint infection with antibiotic.10
An
extended time required (6 days) to sterilize the joint is an indicator of poor prognosis.10
Patient
with polyarthicular septic non gonoccocus arthritis have a very prognosis (approximately 30%
mortality rate) due to a reduced ability to clear the infection and associated bacteremia.
The prognosis of patient s with gonococcal arthritis is very good, with a rapid diminution
of symptoms, and a full return of joint function. In rare case of DGI, complications such as
endocarditis, osteomyelitis, pericarditis, pyomyositis, periphepatitis, and meningitis may occur.10
33
CHAPTER IV
DISCUSSION
4.1 Diagnosis Aspect
The patient was suspected to have septic arthritis at left tibiotalar joint because he had
symptoms that matched the classical presentation of non gonococcal septic arthritis which are
recent onset of fever > 39oC (the patient had 41
oC fever), history of malaise, rigor at his left
ankle joint, mono-articular, and local findings of tenderness, warmth, swelling, and decreased
range of motion in his ankle joint. These findings are consistent with infection/inflamamation,
supported with laboratory findings which are leukocytosis (32,81x109/L) and increase of CRP
and LED (457,65mg/L and 88,4mm/hr). The diagnosis of septic arthritis is confirmed with the
pus culture from the involved joint which is taken at time of surgery, with the bacteria
Staphylococcus aureus as the causal microorganism.
There are many routes by which pathogens accumulate in the joints including:
hematogenously through synovial capillaries, infected contiguous foci, neighboring soft tissue
sepsis, or by direct penetration / insult due to trauma or iatrogenic injury / events such as
diagnostic or therapeutic arthrocentesis of joint surgery. At this patient the route of infection
most probably is hematogenously through synovial capillaries, as no wound or other soft tissue
damage are seen.
While any joint can become infected, the most commonly involved joint in non gonococcal
arthritis are the knee (35.24%) and hip (24.59%), followed by ankle (18.03%). These facts are
quite consistent with the site of infection in our patients which is the ankle.
Imaging studies of septic arthritis are usually non revealing in the first few days of
infection as they are usually normal or show only pre-existing joint disease. However, swelling
capsule and soft tissue around the affected joint, fat pad displacement, and in some assess joint
space widening due to localized edema and effusion may be found. The initial radiographic
image is useful to determined associated conditions or pre-existing joint disease mentioned
before. From our patient’s x-ray taken at early days of infection we can only see some swelling
at the soft tissue around the left tibiotalar joint which extend to proximal metatarsal.
4.2 Management Aspect
Acute non gonococcal arthritis is an emergency that can cause significant even fatal
morbidity and mortality. Aggresive and rapid treatment is essential to prevent any harmful effect
from the disease. Most people with suppurative arthritis respond clinically to appropriate
antimicrobial agents after initial diagnostic aspiration of synovial fluids (SF). Therefore, the
initial antibiotic given should be a broad spectrum based on the gram’s stain and the age and the
risk factors of the patients. and should be given as soon as possible after collection of SF. It is
34
given based on empiric therapy that are confirmed from clinical presentation and clinical course,
physical examination, and analysis and culture of SF. Our patient has been given empirical
antibiotic Cefazolin which is broad spectrum and after the pus culture result is finished and
revealed the causal microorganism (Staphylococcus aureus) and sensitivity test, the appropriate
and definitive antibiotic is given. Unfortunately resistancy problem occured in this patient, which
shown isolated bacteria Methicillin-resistant Staphylococcus aureus at later culture, but we
changed the appropriate antibiotic which are Ciprofloxacin and Gentamicin, and about a week
after that, the patient improved clinically and confirmed by laboratory results which shown
decrease of leukocyte and CRP.
There is no set of universally accepted criteria for choosing the drainage method. The
drainage method used should be customized to each clinical states of each patient. However,
there is general guidelines that should be followed. Patient should be initially treated with needle
joint aspiration if the infection is easily accessible, if the majority if the purulent fluid can be
removed, and if the patient doesn’t have negative prognostic indicator. The majority of the study
concluded that wrist, elbow, ankle, knee initially should be treated with needle aspiration, and
axial joints including hip, shoulder, and sterno-clavicular joint should undergo open surgical
drainage. Our patient undergone 2 surgery to drainage the pus, and combined with proper
antibiotics, the results are satisfied.
Patient has to rest and optimal anatomical joint position has to be positioned to prevent any
deformation and contractures. Splint should be considered to maintain proper joint position (e.g.,
hip in neutral rotation with some abduction, knee in extension fully, elbow in 90 degree flexion,
and forearm in neutral rotation). The isotonic exercise is helpful in preventing atrophy. Early
physical therapy and aggressive mobilization are important part for optimal recovery and
prevention of complication such as contracture and pain. After the infection started to
diminished, the patient had to do physical therapy to prevent any late complications.
35
CHAPTER V
CONCLUSION
Septic arthritis need to be suspected in patients with acute mono-articular arthritis.
Diagnosis of septic arthritis can be challenging even for skilled physician in the management of
musculoskeletal disease. Prompt diagnosis and management of the disease can prevent
significant short and long term complication and mortality. Failure to recognized and initiate
appropriate antibiotic therapy within the first 24 to 48 hours of onset can cause sub-chondral
bone loss and permanent joint dysfunction with case fatality around 11%.
The management include proper antibiotic / antimicrobial agents after initial diagnostic
aspiration of synovial fluids, combined with drainage of the purulent fluid at the involved joint.
Patient has to rest and optimal anatomical joint position has to be positioned to prevent any
deformation and contractures. Early physical therapy and aggresive mobilization are important
part for optimal recovery and prevention of complication such as contracture and pain.
36
REFERENCES
1. García-Arias, M., Balsa, A., & Mola, E. M. Septic arthritis. Best Practice & Research
Clinical Rheumatology 2011;25(3):407–421. doi: 10.1016/j.berh.2011.02.001.
2. Horowitz DL, Katzap E, Horowitz, S., et al. Approach to Septic Arthritis. Am Fam
Physician. 2011;84(6):653-660.
3. Mathews CJ, Weston VC, Jones A, Field M, Coakley G. Bacterial septic arthritis in adults.
Lancet. 2010;375(9717):846-855.
4. Goldenberg DL. Septic arthritis. Lancet. 1998;351(9097):197-202.
5. Gupta MN, Sturrock RD, Field M. A prospective 2-year study of 75 patients with adultonset
septic arthritis. Rheumatology (Oxford) 2001; 40: 24–30.
6. Margaretten, M. E., Kohlwes, J., Moore, D., & Bent, S. Does This Adult Patient Have Septic
Arthritis? JAMA 2007; 297(13). doi:10.1001/jama.297.13.1478
7. Newman JH. Review of septic arthritis throughout the antibiotic era. Ann Rheum Dis 1976;
35: 198–205.
8. Butler BA, et al., Early diagnosis of septic arthritis in immunocompromised patients, Journal
of Orthopaedic Science (2018), doi: https://doi.org/10.1016/j.jos.2018.02.011.
9. Dubost, J.-J., Soubrier, M., De Champs, C., Ristori, J.-M., & Sauvezie, B. Streptococcal
septic arthritis in adults. A study of 55 cases with a literature review. Joint Bone
Spine.2004;71(4):303–311. doi:10.1016/s1297-319x(03)00122-2
10. Shirtliff MA., Mader JT. Acute Septic Arthritis Clinical Microbiology Reviews 2002;
15(4):527-544. doi: 10.1128/CMR.15.4.527–544.2002.
11. Barton, L. L., L. M. Dunkle, and F. H. Habib. 1987. Septic arthritis in childhood. A 13year
review. Am. J. Dis. Child. 197; 141:898–900.
12. Deesomchok, U., and T. Tumrasvin. Clinical study of culture-proven cases of
nongonococcal arthritis. J. Med. Assoc. Thail. 1990; 73:615–623.
13. Dickie, A. S. 1986. Current concepts in the management of infections in bones and joints.
Drugs 32:458–475.
14. Le Dantec, L., F. Maury, R. M. Flipo, S. Laskri, B. Cortet, B. Duquesnoy, and B.
Delcambre. Peripheral pyogenic arthritis. A study of one hundred seventy-nine cases. Rev.
Rhum. Engl. Ed. 1996;63:103–110.
15. Ryden, C., H. S. Tung, V. Nikolaev, A. Engstrom, and A. Oldberg. Staphylococcus aureus
causing osteomyelitis binds to a nonapeptide sequence in bone sialoprotein. Biochem. J.
1997;327:825–829.
16. Kaandorp CJ, Krijnen P, Moens HJ, Habbema JD, van Schaardenburg D. The outcome of
bacterial arthritis: a prospective community-based study. Arthritis Rheum. 1997;40:884-892.
17. Morgan DS, Fisher D, Merianos A, Currie BJ. An 18 year clinical review of septic arthritis
from tropical Australia. Epidemiol Infect. 1996;117:423-428.
18. Sack K. Monoarthritis: differential diagnosis. Am J Med. 1997;102(suppl 1A):30S34S.
37
19. O’Brien JP, Goldenberg DL, Rice PA. Disseminated gonococcal infection: a prospective
analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine
(Baltimore). 1983;62: 395-406.
20. De Jonghe, M., and G. Glaesener. 1995. Type B Haemophilus influenzae infections.
Experience at the Pediatric Hospital of Luxembourg]. Bull. Soc. Sci. Med. GrandDuche
Luxemb. 132:17–20.
21. Yagupsky, P., Y. Bar-Ziv, C. B. Howard, and R. Dagan. 1995. Epidemiology, etiology, and
clinical features of septic arthritis in children younger than 24 months. Arch. Pediatr.
Adolesc. Med. 149:537–540.
22. Le Dantec, L., F. Maury, R. M. Flipo, S. Laskri, B. Cortet, B. Duquesnoy, and B.
Delcambre. 1996. Peripheral pyogenic arthritis. A study of one hundred seventy-nine cases.
Rev. Rhum. Engl. Ed. 63:103–110.
23. Ryan, M. J., R. Kavanagh, P. G. Wall, and B. L. Hazleman. 1997. Bacterial joint infections
in England and Wales: analysis of bacterial isolates over a four year period. Br. J.
Rheumatol. 36:370–373.
24. Centers for Disease Control and Prevention. 2018. Sexually transmitted disease surveillance
2017, p. 15–24. U.S. Department of Health and Human Services, Public Health Service,
Washington, D.C.
25. Goldenberg, D. L., P. L. Chisholm, and P. A. Rice. 1983. Experimental models of bacterial
arthritis: a microbiologic and histopathologic characterization of the arthritis after the
intraarticular injections of Neisseria gonorrhoeae, Staphylococcus aureus, group A
streptococci, and Escherichia coli. J. Rheumatol. 10:5–11.
26. Koss PG. Disseminated gonococal infection. Cleve Clin Q 1985;52:161-173
27. Nilsson, IM., Patti JM., Bremell T., Hook M., et al. Vaccination with a recombinant
fragment of collagen adhesion provides protection against Staphylococcal polysaccharide
microcapsule expression in septicemia and septic arthritis. J. Clin. Investig. 1998;101:2640-
2649.
28. M., J. M. Patti, T. Bremell, M. Hook, and A. Tarkowski. 1998. Vaccination with a
recombinant fragment of collagen adhesin provides protection against Staphylococcus
aureus-mediated septic death. J. Clin. Investig. 101:2640–2649.
29. Herrmann, M., P. E. Vaudaux, D. Pittet, R. Auckenthaler, P. D. Lew, F.
SchumacherPerdreau, G. Peters, and F. A. Waldvogel. 1988. Fibronectin, fibrinogen, and
laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material.
J. Infect. Dis. 158:693–701.
30. Peacock, S. J., N. P. Day, M. G. Thomas, A. R. Berendt, and T. J. Foster. 2000. Clinical
isolates of Staphylococcus aureus exhibit diversity in fnb genes and adhesion to human
fibronectin. J. Infect. 41:23–31.
31. Bayles, K. W., C. A. Wesson, L. E. Liou, L. K. Fox, G. A. Bohach, and W. R. Trumble.
1998. Intracellular Staphylococcus aureus escapes the endosome and induces apoptosis in
epithelial cells. Infect. Immun. 66:336–342.
32. Lammers, A., P. J. Nuijten, and H. E. Smith. 1999. The fibronectin binding proteins of
Staphylococcus aureus are required for adhesion to and invasion of bovine mammary gland
cells. FEMS Microbiol. Lett. 180:103–109.
38
33. Menzies, B. E., and I. Kourteva. 1998. Internalization of Staphylococcus aureus by
endothelial cells induces apoptosis. Infect. Immun. 66:5994–5998
34. Wesson, C. A., J. Deringer, L. E. Liou, K. W. Bayles, G. A. Bohach, and W. R. Trumble.
2000. Apoptosis induced by Staphylococcus aureus in epithelial cells utilizes a mechanism
involving caspases 8 and 3. Infect. Immun. 68:2998–3001.
35. Koch, B., P. Lemmermeier, A. Gause, H. Wilamowsky, J. Heisel, and M. Pfreundschuh.
1996. Demonstration of interleukin-1beta and interleukin-6 in cells of synovial fluids by
flow cytometry. Eur. J. Med. Res. 1:244–248.
36. Vincent, G. M., and J. D. Amirault. 1990. Septic arthritis in the elderly. Clin. Orthop.
251:241–245.
37. Gutierrez K. Bone and joint infections in children. Pediatric Clinics of North America
2005;52:779–94.
38. Abdelnour, A., T. Bremell, R. Holmdahl, and A. Tarkowski. 1994. Role of T lymphocytes in
experimental Staphylococcus aureus arthritis. Scand. J. Immunol. 39:403–408.
39. Dinarello C. Mier J. Lymphokines. N Engl J Med 1987:317:940- 5.
40. Dinarello C. The proinflammatory cytokines interleukin-1 and tumor necrosis factor and
treatment ofthe septic shock syndrome. JID 1991:163:1177-83.
41. Springer T. Adhesion receptors of the immune system. Nature 1990:346:425-34.
42. Cheung A, Koomey J, Lee S, Jaffe E. Fihcetti V. Recombinant human tumor necrosis factor
alpha promotes adherence of Staphylococcus aureus to cultured human endothelial cells
Infect Immun 1991:59:3827-31.
43. Deng, G. M., I. M. Nilsson, M. Verdrengh, L. V. Collins, and A. Tarkowski. 1999. Intra-
articularly localized bacterial DNA containing CpG motifs induces arthritis. Nat. Med.
5:702–705.
44. Deng, G. M., and A. Tarkowski. 2000. The features of arthritis induced by CpG motifs in
bacterial DNA. Arthritis Rheum. 43:356–364.
45. Bremell, T., and A. Tarkowski. 1995. Preferential induction of septic arthritis and mortality
by superantigen-producing staphylococci. Infect. Immun. 63:4185–4187.
46. Littlewood-Evans, A. J., M. R. Hattenberger, C. Luscher, A. Pataki, O. Zak, and T.
O’Reilly. 1997. Local expression of tumor necrosis factor alpha in an experimental model of
acute osteomyelitis in rats. Infect. Immun. 65:3438– 3443.
47. Nair, S. P., S. Meghji, M. Wilson, K. Reddi, P. White, and B. Henderson. 1996. Bacterially
induced bone destruction: mechanisms and misconceptions. Infect. Immun. 64:2371–2380.
48. Wilson, M., S. Meghji, and W. Harvey. 1986. Inhibition of bone collagen synthesis in vitro
by lipopolysaccharide from Actinobacillus actinomycetemcomitans. IRCS Med. Sci.
14:536–537.
49. Lowe, A. M., D. T. Beattie, and R. L. Deresiewicz. 1998. Identification of novel
staphylococcal virulence genes by in vivo expression technology. Mol. Microbiol. 27:967–
976.
50. Swaminathan A, Massasso D, Gotis-Graham I, Gosbell I. Fulminant methicillinsensitive
Staphylococcus aureus infection in a healthy adolescent, highlighting ‘Panton-Valentine
leucocidin syndrome’. Intern Med J 2006; 36: 744–47.
39
51. Weston VC, Jones AC, Bradbury N, Fawthrop F, Doherty M. Clinical features and outcome
of septic arthritis in a single UK Health District 1982–1991. Annals of the Rheumatic
Diseases 1999;58:214–9.
52. Barton, L. L., L. M. Dunkle, and F. H. Habib. 1987. Septic arthritis in childhood. A 13year
review. Am. J. Dis. Child. 141:898–900.
53. Ho, G. J., and E. Y. Su. 1982. Therapy for septic arthritis. JAMA 247:797– 800.
54. Jackson, M. A., and J. D. Nelson. 1982. Etiology and medical management of acute
suppurative bone and joint infections in pediatric patients. J. Pediatr. Orthop. 2:313– 323.
55. Sharp, J. T., M. D. Lidsky, J. Duffy, and M. W. Duncan. 1979. Infectious arthritis. Arch.
Intern. Med. 139:1125–1130.
56. Shmerling, R. H., T. L. Delbanco, A. N. Tosteson, and D. E. Trentham. 1990. Synovial fluid
tests. What should be ordered? JAMA 264:1009–1014.
57. Krey PR, Bailen DA. Synovial fluid leukocytosis: a study of extremes. Am J Med.
1979;67:436-44.
58. Shiv, V. K., A. K. Jain, K. Taneja, and S. K. Bhargava. 1990. Sonography of hip joint in
infective arthritis. Can. Assoc. Radiol. J. 41:76–78.
59. Zeiger, M. M., U. Dorr, and R. D. Schulz. 1987. Ultrasonography of hip joint effusions.
Skeletal Radiol. 16:607–611.
60. Sandrasegaran, K., A. Saifuddin, A. Coral, and W. P. Butt. 1994. Magnetic resonance
imaging of septic sacroiliitis. Skeletal Radiol. 23:289–292.
61. Erdman, W. A., F. Tamburro, H. T. Jayson, P. T. Weatherall, K. B. Ferry, and R. M.
Peshock. 1991. Osteomyelitis: characteristics and pitfalls of diagnosis with MR imaging.
Radiology 180:533–539.
62. Rosenthall, L., R. Lisbona, M. Hernandez, and A. Hadjipavlou. 1979. 99mTc-PP and 67Ga
imaging following insertion of orthopedic devices. Radiology 133:717–721.
63. Bittini, A., P. L. Dominguez, P. M. Martinez, L. F. Lopez, I. Monteagudo, and L. Carreno.
1985. Comparison of bone and gallium-67 imaging in heroin users’ arthritis. J. Nucl. Med.
26:1377–1381.
64. Liebling, M. R., D. G. Arkfeld, G. A. Michelini, M. J. Nishio, B. J. Eng, T. Jin, and J. S.
Louie. 1994. Identification of Neisseria gonorrhoeae in synovial fluid using the polymerase
chain reaction. Arthritis Rheum. 37:702–709.
65. Baker DG, Schumacher HR Jr. Acute monoarthritis. N Engl J Med 1993; 329: 1013– 20.
66. Cuellar, M. L., L. H. Silveira, and L. R. Espinoza. 1992. Fungal arthritis. Ann. Rheum. Dis.
51:690–697.
67. Garrido, G., J. J. Gomez-Reino, P. Fernandez-Dapica, E. Palenque, and S. Prieto. 1988. A
review of peripheral tuberculous arthritis. Semin. Arthritis Rheum. 18:142–149.
68. Hamed KA, Tam JY, Prober CG. Pharmacokinetic optimisation of the treatment of septic
arthritis. Clin Pharmacokinet 1996; 21: 156–63.
69. Goldenberg, D. L., and J. I. Reed. 1985. Bacterial arthritis. N. Engl. J. Med. 312:764– 771.
70. Rosenthal, J., G. G. Bole, and W. D. Robinson. 1980. Acute nongonococcal infectious
arthritis. Evaluation of risk factors, therapy, and outcome. Arthritis Rheum. 23:889– 897.
40
71. Goldenberg, D. L. and A. S. Cohen. 1976. Acute infectious arthritis. A review of patients
with nongonococcal joint infections (with emphasis on therapy and prognosis). Am. J. Med.
60:369–377.
72. Knights, E. M. 1982. Infectious arthritis. J. Foot Surg. 21:229–233.
73. Odio CM, Ramirez T, Arias G, Abdelnour A, Hidalgo I, Herrera ML, et al. Double blind,
randomized, placebo-controlled study of dexamethasone therapy for hematogenous septic
arthritis in children. Journal of Pediatric Infectious Diseases 2003;22:883–8.
74. Tarkowski A. Infection and musculoskeletal conditions: Infectious arthritis. Best Practice &
Research Clinical Rheumatology 2006;20:1029–44.
75. Puliti M, von Hunolstein C, Verwaerde C, Bistoni F, Orefici G, Tissi L. Regulatory role of
interleukin-10 in experimental group B streptococcal arthritis. Infection and Immunity
2002;70:2862–8.
76. Puliti M, von Hunolstein C, Bistoni F, Mosci P, Orefici G, Tissi L. The beneficial effect of
interleukin-12 on arthritis induced by group B streptococci in mediated by interferongamma
and interleukin-10 production. Arthritis & Rheumatism 2002; 46:806–17.
77. Verdrengh M, Carlsten H, Ohlsson C, Tarkowski A. Addition of bisphosphonate to
antibiotic and anti-inflammatory treatment reduces bone resorption in experimental
Staphylococcus aureus-induced arthritis. Journal of Orthopaedic Research 2007;25:304–10.
78. Ison CA, Dillon JA, Tapsall JW. The epidemiology of global antibiotic resistance among
Neisseria gonorrhoeae and Haemophilus ducreyi. Lancet 1998;3(351 Suppl):8– 11.
79. Bardin T. Gonococcal arthritis. Best Practice & Research Clinical Rheumatology
2003;17:201–8.
80. Centers for Disease Control and Prevention. 1998. 1998 guidelines for treatment of sexually
transmitted diseases. Morb. Mortal. Wkly. Rep. 47: 1–111.
81. Centers for Disease Control and Prevention. 2000. Sexually transmitted disease surveillance
1999, p. 15–24. U.S. Department of Health and Human Services, Public Health Service,
Washington, D.C.
82. Bengtson, S., and K. Knutson. 1991. The infected knee arthroplasty. A 6-year followup of
357 cases. Acta Orthop. Scand. 62:301–311.
83. Roisman, F. R., D. T. Walz, and A. E. Finkelstein. 1983. Superoxide radical production by
human leukocytes exposed to immune complexes: inhibitory action of gold compounds.
Inflammation 7:355–362.
84. Phillips JE, Crane TP, Noy M, Elliott TS, Grimer RJ. The incidence of deep prosthetic
infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone Joint
Surg Br. 2006;88(7):943-948.
85. Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement: a
retrospective review of 6489 total knee replacements. Clin Orthop Relat Res. 2001;(392):15-
23.