Performance of established test methods in diagnosing persistent infection at the second stage of a two-stage procedure for periprosthetic hip and knee infections

Aims This study aims to evaluate the diagnostic performance of serum parameters, synovial fluid analysis, tissue and sonication fluid cultures, and histology to identify persistent infection, and to predict reinfection at reimplantation of two-stage exchange arthroplasty. Methods From January 2015 to January 2023, a total of 133 patients with completed two-stage exchange arthroplasty for periprosthetic joint infection (PJI) following total hip or knee arthroplasty were eligible for inclusion in this retrospective study. Diagnostic values of serum parameters (CRP, white blood cell count (WBC), differential, fibrinogen), synovial fluid WBC (SF-WBC), culture (synovial fluid, tissue, sonication fluid), and histology were evaluated prior to or at the second stage. Additionally, Kaplan-Meier curves were used to determine infection-free prosthesis survival rates for all parameters. Results Serum CRP showed the highest area under the receiver operating characteristic curve (AUC; 0.624) among all analyzed test methods (serum WBC: 0.501; serum % polymorphonuclear neutrophils (PMN): 0.605; fibrinogen: 0.533; SF-WBC: 0.601; SF culture: 0.566; tissue culture: 0.463; sonication fluid culture: 0.473; histology: 0.492). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CRP were 51.7% (95% CI 35 to 69), 73.1% (95% CI 64 to 81), 34.9% (95% CI 21 to 49), and 84.4% (95% CI 77 to 92), respectively. In 35% (n = 15/43) of patients with an elevated serum CRP (≥ 10 mg/l), reinfection occurred, while the reinfection rate was only 16% (n = 14/90) in patients with a normal CRP (< 10 mg/l, p = 0.012). Reinfection rates in patients with all-negative cultures at 23% were not significantly different from cases with positive cultures at 13% (p = 0.352). Conclusion Although CRP showed the best diagnostic value among all analyzed test methods, none of them could reliably identify persistent infection or predict reinfection. Additionally, a positive culture may not justify a further intervention (spacer exchange, prolonged antibiotics). In case of positive culture or elevated CRP, a further thorough debridement at the second stage is recommended to increase the chance of infection eradication. Cite this article: Bone Jt Open 2025;6(10):1190–1198.