Clinical comment

Identification of the microbial pathogen(s) is essential for diagnosis of TKA infection and for selection of appropriate pathogen‐specific antimicrobial therapy. There has been growing interest in using nonculture‐based methods to diagnose TKA infection.

Available literature and quality of the evidence

Level I and II evidence exists to answer this question.

Findings

The initial history and physical exam are crucial to the diagnosis of periprosthetic joint infection (PJI). Patient risk factors and perioperative risk factors should be identified.² Blood tests, including serum ESR and CRP have high sensitivity, good negative predictive value, and are cost‐effective screening tools.³ ESR sensitivity and specificity are 75% (95% confidence interval [CI]: 72–77%) and 70% (95% CI: 68–72%), respectively.⁴ CRP sensitivity and specificity are 88% (95% CI: 86–90%) and 74% (95% CI: 71–76%), respectively.⁴ These blood tests can be used as adjuncts to synovial fluid cytology with WBC differential and synovial fluid culture, which have sensitivities of 90% (95% CI: 78–96%) and 62% (95% CI: 50–74%) and specificities of 91% (95% CI: 80–96%) and 94% (95% CI: 91–96%), respectively, for diagnosis of TKA infection.^5,6 Since inflammatory markers such as ESR and CRP may remain elevated for up to several months following primary TKA, they may be less useful for identifying early postoperative infection.⁷ Thresholds for chronic PJI have been identified.⁸

With sensitivity and specificity of 45% (95% CI: 41–49%) and 87% (95% CI: 85–89%), respectively, serum WBC count is not as useful as serum ESR or CRP for diagnosis of TKA infection.^2,4 Serum interleukin 6 (IL‐6) may be a more specific marker of acute infection, but it is not be available in all laboratories.² Estimated sensitivity and specificity for IL‐6 are 97% (95% CI: 93–99%) and 91% (95% CI: 87–94%), respectively.⁴ Overall, the diagnostic accuracy for PJI is best for IL‐6, followed by CRP, ESR, and WBC count.⁴

A novel approach to PJI diagnosis involves synovial fluid inflammatory biomarkers, such as alpha‐defensin. The alpha‐defensin assay offers another test with excellent sensitivity and specificity (100% CI: 79–100% and 95% CI: 83–99%, respectively) for diagnosis of PJI, and it is now available for clinical use.^2,9,10 Though preliminary data suggest that alpha‐defensin 1 is at least equivalent to other diagnostic modalities, larger studies are required to confirm this finding.¹⁰

Clinical resolution

• ESR and CRP have excellent diagnostic test performance for chronic TKA infection and should be used as initial screening tools and adjuncts to synovial fluid cytology and culture (level I).
  
• The diagnostic accuracy of preoperative serologic investigations for PJI is best for IL‐6, followed by CRP, ESR, and WBC count (level II).
  
• Emerging investigations, such as serum IL‐6 and synovial alpha‐defensin testing, demonstrate improved sensitivity and specificity for detecting TKA infection (level II).