What is the best approach to diagnose the pathogens responsible for a prosthetic knee infection in an older adult with a history of previous infections or antibiotic use?

Diagnostic Approach to Prosthetic Knee Infection in Older Adults with Prior Antibiotic Exposure

In older adults with prosthetic knee infection and previous antibiotic use, withhold antimicrobials for at least 2 weeks before obtaining specimens, then collect 5-6 intraoperative tissue samples for prolonged aerobic and anaerobic culture (up to 14 days), combined with preoperative ESR/CRP testing and synovial fluid analysis showing >1700 cells/μL or >65% neutrophils. 1

Preoperative Diagnostic Strategy

Serologic Testing

• Obtain both ESR and CRP levels as initial screening tests - when both are negative, infection is unlikely and further invasive testing may not be warranted 1
• CRP demonstrates 73-91% sensitivity and 81-86% specificity using a cutoff of ≥13.5 mg/L for prosthetic knee infection 1
• ESR cutoff of ≥27 mm/h combined with CRP ≥0.93 mg/L provides 93% sensitivity and 100% specificity when both are abnormal 1

Synovial Fluid Analysis

• Perform joint aspiration when ESR or CRP is elevated - this represents the most useful diagnostic tool alongside CRP 1
• Synovial fluid leukocyte count >1700 cells/μL has 94% sensitivity for infection in patients >6 months post-implantation 1
• Neutrophil differential >65% demonstrates 97% sensitivity for detecting infection 1
• Send aspirated fluid for aerobic and anaerobic culture with prolonged incubation 1

Critical Antibiotic Timing Consideration

Withhold antimicrobial therapy for at least 2 weeks prior to specimen collection to maximize organism recovery - this is particularly crucial in patients with prior antibiotic exposure 1

Intraoperative Diagnostic Approach

Tissue Sampling Protocol

• Obtain at least 3 and optimally 5-6 periprosthetic tissue samples from the most suspicious areas for aerobic and anaerobic culture 1
• Submitting fewer than 5-6 specimens significantly decreases diagnostic sensitivity 1
• Request prolonged incubation up to 14 days, especially important for low-virulence organisms like Propionibacterium species and coagulase-negative staphylococci 1

Prosthesis Sonication

• Submit the explanted prosthesis for sonication and culture of the sonicate fluid - this technique demonstrates 78.5% sensitivity compared to 60.8% for single tissue culture (P<0.001) 1
• Sonication dislodges biofilm bacteria from the prosthesis surface, improving pathogen detection 1
• Note that sonication is not validated for fungal or mycobacterial organisms 1

Histopathology

• Intraoperative frozen section analysis provides >80% sensitivity and >90% specificity when performed by experienced pathologists 1
• Acute inflammation may be less prominent with low-virulence organisms like coagulase-negative staphylococci 1

Interpretation of Culture Results

Defining Definitive Infection

• Growth of identical organisms in ≥2 separate tissue or fluid samples constitutes definitive evidence of PJI 1
• A single culture growing virulent organisms (e.g., S. aureus) may represent true infection 1
• Single cultures growing common contaminants (coagulase-negative staphylococci, Propionibacterium acnes) require clinical correlation - do not automatically diagnose infection based on one positive culture 1

Special Considerations for This Population

Coagulase-negative staphylococci warrant particular attention - these biofilm-producing organisms show 63% methicillin resistance rates and are associated with only 47% treatment success at one year, with higher rates in polymicrobial infections (60% of polymicrobial vs 35% of monomicrobial cases) 2, 3

In patients with prior antibiotic exposure, polymicrobial infections are more common - these occur more frequently with shorter time from implantation to symptoms and show different microbiology than monomicrobial infections 3

Common Pitfalls to Avoid

• Do not rely on Gram stain - it has low sensitivity on tissue specimens and is not routinely useful 1
• Do not give antimicrobial prophylaxis before revision surgery when PJI risk is high - this compromises culture yield 1
• Do not dismiss single positive cultures of coagulase-negative staphylococci without clinical context - these may represent true infection, particularly in biofilm-associated disease 2, 3
• Do not use standard 5-day culture incubation - prolonged incubation up to 14 days is necessary for slow-growing organisms 1

Clinical Decision Algorithm

1. Measure ESR and CRP - if both negative, infection unlikely 1
2. If either ESR or CRP elevated → perform joint aspiration for cell count, differential, and culture 1
3. Withhold antibiotics ≥2 weeks before any specimen collection when clinically safe 1
4. At surgery, obtain 5-6 tissue samples plus prosthesis for sonication 1
5. Request 14-day culture incubation for all specimens 1
6. Diagnose infection when ≥2 cultures grow identical organisms or clinical judgment supports infection despite negative cultures 1