What are the recommended laboratory tests for a suspected knee joint infection?

Recommended Laboratory Tests for Suspected Knee Joint Infection

For suspected knee joint infection, the recommended laboratory tests include serum ESR, CRP, serum interleukin-6, and joint aspiration with synovial fluid analysis for cell count, differential, culture, and alpha-defensin testing. 1

Initial Serum Laboratory Tests

• Erythrocyte Sedimentation Rate (ESR)

  • Cutoff value: >27 mm/h 1
  • Sensitivity: 85% for chronic periprosthetic joint infection 2
  • Note: May remain elevated for up to 2 months after surgery 1

• C-Reactive Protein (CRP)

  • Cutoff value: >10 mg/L 1
  • Sensitivity: 88% for chronic periprosthetic joint infection 2
  • Returns to baseline within 2 months after surgery 1
  • Higher values typically seen with infection compared to aseptic loosening 1

• Serum Interleukin-6

  • Strongly recommended by AAOS guidelines 1
  • Higher predictive values than most other serologic markers 1
  • Excellent sensitivity when combined with CRP 1

• Serum D-dimer

  • Recommended as part of the preoperative workup 1

Diagnostic Algorithm

1. Initial Screening:

   • If both ESR and CRP are negative, infection is unlikely (high negative predictive value) 1
   • If either ESR or CRP is elevated, proceed to joint aspiration 1

2. Joint Aspiration (preferably with ultrasound or fluoroscopic guidance):

   • Synovial fluid analysis should include:
     • White blood cell count and differential
     • Gram stain
     • Aerobic and anaerobic cultures
     • Alpha-defensin test
     • Leukocyte esterase
     • Synovial fluid CRP 1

3. Interpretation of Synovial Fluid Analysis:

   • For native knee joint infection:

     • Traditional threshold: WBC count ≥50,000 cells/mm³ with >60% PMNs indicates high suspicion for septic arthritis 3, 4
     • Note: Recent research suggests not excluding diagnosis even with lower values 4

   • For prosthetic knee joint infection:

     • WBC count >1,100-3,000 cells/mm³ 5, 6, 7
     • Neutrophil percentage >64-72% 6, 7
     • Synovial fluid alpha-defensin test: 97% sensitivity, 96% specificity 1
     • Combination of synovial fluid alpha-defensin and CRP: 97% sensitivity, 100% specificity 1

Important Clinical Considerations

• Peripheral leukocyte counts are often not elevated in prosthetic joint infections and have limited diagnostic value 1

• False negatives are common with:

  • Low-virulence organisms
  • Culture-negative cases
  • Prior antibiotic use 2

• If clinical suspicion remains high despite negative initial aspiration:

  • Discontinue antibiotics for at least 2 weeks before repeating aspiration 1
  • Consider weekly repeat aspirations 1

• Diagnostic accuracy is improved when combining:

  • Synovial fluid cell count and differential
  • Serum inflammatory markers (ESR, CRP)
  • Multiple cultures 7

• The combination of abnormal results for at least 2 of 3 tests (CRP, ESR, and fibrinogen) has shown excellent diagnostic accuracy (sensitivity 93%, specificity 100%) 1

• Serologic tests may be difficult to interpret in patients with underlying inflammatory arthropathies 1