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Arthritis, Septic
Jeffrey P. Feden, MD, FACEP
image BASICS
DESCRIPTION
  • Infection due to bacterial invasion of the joint space
  • Systems affected: musculoskeletal
  • Synonyms: suppurative arthritis; infectious arthritis; pyarthrosis; pyogenic arthritis; bacterial arthritis
EPIDEMIOLOGY
  • May occur at any age; higher incidence in very young and elderly
  • Incidence:
    • 4 to 10/100,000 annual case rate (1)
  • Prevalence: 27% of patients presenting with monoarticular arthritis have nongonococcal septic arthritis (2).
  • Gender differences:
    • Gonococcal: female > male
    • Nongonococcal: male > female
ETIOLOGY AND PATHOPHYSIOLOGY
  • Many different pathogenic organisms
  • Nongonococcal:
    • Staphylococcus aureus (most common organism in adults)
  • MRSA risk increased in elderly, intravenous drug users (IVDU), postsurgical
    • Streptococcus spp. (second most common in adults)
    • Gram-negative rods (GNR): IVDU, trauma, extremes of age, immunosuppressed
  • Neisseria gonorrhea (most common in young, sexually active adults)
  • Other: rickettsial (e.g., Lyme), fungal, mycobacterial
  • Risk by specific age (3):
    • <1 month: Streptococcus aureus, Group B strep (GBS), GNR
    • 1 month to 4 years: Streptococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis
    • 16 to 40 years: N. meningitidis, S. aureus
    • >40 years: S. aureus
  • Specific high-risk groups:
    • Rheumatoid arthritis: S. aureus
    • IVDU: S. aureus, GNR, opportunistic pathogens
    • Neonates: GBS
    • Immunocompromised: gram-negative bacilli, fungi
    • Trauma patients with open injuries: mixed flora
  • Pathogenesis:
    • Hematogenous spread (most common)
    • Direct inoculation by microorganisms secondary to trauma or iatrogenesis (e.g., joint surgery)
    • Adjacent spread (e.g., osteomyelitis)
  • Pathophysiology:
    • Microorganisms initially enter through synovial membrane and spread to the synovial fluid.
    • Resulting inflammatory response releases cytokines and destructive proteases leading to joint damage.
    • Microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) on bacteria influence disease progression (4).
RISK FACTORS
  • Age >80 years
  • Low socioeconomic status; alcoholism
  • Cellulitis and skin ulcers
  • Prior violation of joint capsule
    • Prior orthopedic surgery
    • Intra-articular steroid injection
    • Trauma
  • History of previous joint disease
    • Inflammatory arthritis (rheumatoid arthritis [RA]: 10-fold increased risk)
    • Osteoarthritis
    • Crystal arthritides
  • Systemic illness
    • Diabetes mellitus, liver disease, HIV, malignancy, end-stage renal disease/hemodialysis, immunosuppression, sickle cell anemia
  • Risks for hematogenous spread
    • IVDU, severe sepsis/systemic infection
GENERAL PREVENTION
  • Prompt treatment of skin and soft tissue infections
  • Control risk factors
  • Immunization (S. pneumoniae; N. meningitidis)
image DIAGNOSIS
PHYSICAL EXAM
  • Physical exam generally has poor sensitivity and specificity in the context of septic arthritis. Common findings include:
    • Limited range of motion
    • Joint effusion and tenderness
    • Erythema and warmth over affected joint
    • Pain with passive range of motion
  • Septic arthritis of hip and shoulder involvement may reveal severe pain on range of motion and less obvious swelling on exam.
  • Pediatric consideration: Infants with septic hip arthritis, keep the joint flexed and externally rotated.
DIFFERENTIAL DIAGNOSIS
  • Crystal arthritis: gout, pseudogout, calcium oxalate, cholesterol
  • Infectious arthritis: fungi, spirochetes, rheumatic fever, HIV, viral
  • Inflammatory arthritis: RA, spondyloarthropathy, systemic lupus erythematosus, sarcoidosis
  • Osteoarthritis
  • Trauma: meniscal tear, fracture, hemarthrosis
  • Other: bursitis, cellulitis, tendinitis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Synovial fluid analysis (gold standard):
    • Obtain prior to antibiotic therapy if possible
    • Include Gram stain, culture, cell count/differential, and crystal analysis.
    • Use blood culture bottles to increase yield.
    • Gram stain (positive in 50%) and culture (positive in 50-70%) should be sent with understanding of limitations.
    • >50,000 WBCs/HPF with >90% polymorphonuclear leukocytes is considered suggestive; however, synovial WBC (sWBC) count alone is insufficient to rule in or rule out septic arthritis (3)[A].
    • The presence of crystals (e.g., urate or calcium pyrophosphate) does not exclude concurrent infectious arthritis (5).
    • Prosthetic joint: WBC count is unreliable; a lower number of sWBCs may indicate infection.
  • Serum tests:
    • WBC count alone is neither sensitive nor specific.
    • ESR with cutoff of >15 mm/hr has sensitivity up to 94% but poor specificity (6)[B].
    • CRP >20 mg/L has sensitivity of 92% (6)[B].
    • Serum procalcitonin >0.4 ng/mL has 85% sensitivity and 87% specificity (7)[B].
    • Synovial lactate is a potential biomarker (8,9)[C].
    • Blood cultures are positive in 50% of cases.
  • Other tests:
    • Disseminated gonococcus: culture blood, cervix, urine, urethra, pharynx in addition to joint fluid
    • Suspected Lyme arthritis: send serum Lyme titers
  • Pediatrics: No single lab test distinguishes septic arthritis from transient synovitis.
    • The combination of fever, non-weight bearing, and elevated ESR and CRP is suspicious, but synovial fluid should still be obtained.
  • Imaging: helpful to identify effusion but does not differentiate septic from other forms of arthritis
    • Plain films:
      • Nondiagnostic for septic arthritis. Useful for other pathology such as trauma, soft tissue swelling, osteoarthritis, or osteopenia
      • May show nonspecific changes of inflammatory arthritis (i.e., erosions, joint destruction, joint space loss)
    • Ultrasound:
      • Identifies joint space to guide arthrocentesis
      • Recommended for aspiration of the hip
    • MRI:
      • Highly sensitive for effusion; increasing role to distinguish between transient synovitis and septic arthritis in children (10)[B]
    • Other imaging techniques:
      • CT is not routinely indicated.
      • Bone scans are not performed unless there is suspicion for osteomyelitis.
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Diagnostic Procedures/Other
Arthrocentesis in all suspected cases (prior to initiation of antibiotics). Avoid contaminated tissue (e.g., overlying cellulitis) when performing arthrocentesis.
Test Interpretation
Synovial biopsy shows polymorphonuclear leukocytes and possibly the causative organism.
image TREATMENT
GENERAL MEASURES
  • Admit for parenteral antibiotics and monitoring. Antibiotics should begin immediately after arthrocentesis is performed and cultures requested.
  • Removal of purulent material is required in these cases:
    • Pediatric: Surgical drainage and irrigation is recommended if hip involved due to high risk of avascular necrosis.
    • Prosthetic joint: Antibiotics and consult with orthopedics for consideration of replacement arthroplasty, resection arthroplasty, or d├ębridement (11)[B].
  • Treat for a total of 4 to 6 weeks in most cases.
    • Exception: gonococcal (2 to 3 weeks)
  • Intra-articular antibiotics are not recommended.
  • IV dexamethasone in conjunction with antibiotics may reduce long-term sequelae and improve recovery time in pediatric patients (12)[A].
MEDICATION
First Line
  • Initial antibiotic choice is guided by Gram stain or most likely organism based on age and clinical history.
  • Nongonococcal (13)[A]:
    • Gram-positive cocci:
      • Vancomycin 15 to 20 mg/kg 2 to 3 times daily or linezolid 600 mg twice daily
    • Gram-negative bacilli:
      • Cefepime 2 g twice daily or ceftriaxone 2 g daily or ceftazidime 2 g, 3 times daily or cefotaxime 2 g, 3 times daily
      • For cephalosporin allergy: Consider treatment with ciprofloxacin 400 mg, 3 times daily.
    • Negative Gram stain:
      • Vancomycin 15 to 20 mg/kg 2 to 3 times daily plus 3rd-generation cephalosporin until cultures and susceptibilities return
    • Duration of therapy: typically 2 weeks of IV and an additional 2 to 4 weeks PO while monitoring therapeutic response
  • Gonococcal (14)[A]:
    • Ceftriaxone 1 g IV/IM daily for 7 to 14 days (and at least 24 to 48 hours after symptoms resolve)
    • May require concurrent drainage of affected joint
    • Concomitant treatment for Chlamydia (doxycycline 100 mg twice daily or azithromycin 1 g daily)
  • Other considerations:
    • Narrow antibiotic therapy based on culture results
    • Consider Salmonella in pediatric patients with a history of sickle cell disease: 3rd-generation cephalosporin helpful in this instance.
    • Lyme arthritis: doxycycline 100 mg PO twice daily or amoxicillin 500 mg PO 3 times daily for 28 days if no neurologic involvement, otherwise ceftriaxone 2 g IV daily (15)[A]
ISSUES FOR REFERRAL
  • Infectious disease and orthopedic consultations
  • IVDU and immunosuppression warrant infectious disease consultation to guide therapy. Prosthetic joint infection is best managed with orthopedic consultation.
SURGERY/OTHER PROCEDURES
  • Consider drainage in all cases, particularly shoulder, hip, and prosthetic joints.
  • Other treatment options include repeat needle aspiration, arthroscopy, or arthrotomy.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Monitor synovial fluid to verify decreasing WBC and sterile fluid after initial treatment.
  • If no improvement within 24 hours, reevaluate and consider arthroscopy.
  • Follow-up at 1 week and 1 month after stopping antibiotics to ensure no relapse.
PROGNOSIS
  • Early treatment improves functional outcome.
  • Delayed recognition/treatment is associated with higher morbidity and mortality.
  • Elderly, concurrent rheumatoid arthritis, S. aureus infections, and infection of hip and shoulder also increase risk of poor outcome.
REFERENCES
1. Geirsson AJ, Statkevicius S, Vikingsson A. Septic arthritis in Iceland 1990-2002: increasing incidence due to iatrogenic infections. Ann Rheum Dis. 2008;67(5):638-643.
2. Mathews CJ, Weston VC, Jones A, et al. Bacterial septic arthritis in adults. Lancet. 2010;375(9717):846-855.
3. Margaretten ME, Kohlwes J, Moore D, et al. Does this adult patient have septic arthritis? JAMA. 2007;297(13):1478-1488.
4. Shirtliff ME, Mader JT. Acute septic arthritis. Clin Microbiol Rev. 2002;15(4):527-544.
5. Shah K, Spear J, Nathanson LA, et al. Does the presence of crystal arthritis rule out septic arthritis? J Emerg Med. 2007;32(1):23-26.
6. Hariharan P, Kabrhel C. Sensitivity of erythrocyte sedimentation rate and C-reactive protein for the exclusion of septic arthritis in emergency department patients. J Emerg Med. 2011;40(4):428-431.
7. Maharajan K, Patro DK, Menon J, et al. Serum Procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis. J Orthop Surg Res. 2013;8:19.
8. Lenski M, Scherer MA. The significance of interleukin-6 and lactate in the synovial fluid for diagnosing native septic arthritis. Acta Orthop Belg. 2014;80(1):18-25.
9. Carpenter CR, Schuur JD, Everett WW, et al. Evidence-based diagnostics: adult septic arthritis. Acad Emerg Med. 2011;18(8):781-796.
10. Yang WJ, Im SA, Lim GY, et al. MR imaging of transient synovitis: differentiation from septic arthritis. Pediatr Radiol. 2006;36(11):1154-1158.
11. Mittal Y, Fehring TK, Hanssen A, et al. Two-stage reimplantation for periprosthetic knee infection involving resistant organisms. J Bone Joint Surg Am. 2007;89(6):1227-1231.
12. Macchiaiolo M, Buonuomo PS, Mennini M, et al. Question 2: should steroids be used in the treatment of septic arthritis? Arch Dis Child. 2014;99(8):785-787.
13. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55.
14. Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55(RR-11):1-94.
15. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.
Codes
ICD10
  • M00.9 Pyogenic arthritis, unspecified
  • M00.20 Other Streptococcal arthritis, unspecified joint
  • M00.00 Staphylococcal arthritis, unspecified joint
Clinical Pearls
  • Because history, exam, and serum markers often confer little diagnostic benefit, arthrocentesis and synovial fluid analysis are mandatory in cases of suspected septic arthritis.
  • Early IV antibiotics and drainage of infected joints are critical to successful management.
  • Crystalline disease may coexist with septic arthritis.
  • Initial antibiotic therapy is guided by results of aspiration (Gram stain), age, and patient-specific risk factors.