Predictors of Failure After Two-Stage Revision for Periprosthetic Joint Infections of the Knee.

Background: Prosthetic joint infection (PJI) following total knee arthroplasty remains a serious complication. Although two-stage revision is considered the gold standard, predictors of failure remain unclear. This study aimed to identify factors associated with failure after two-stage revision for knee PJI using conventional statistics with exploratory machine-learning validation. Methods: A retrospective review was conducted on 154 patients who underwent two-stage revision for knee PJI between 2018 and 2022 at a high-volume arthroplasty center. All patients completed a minimum 24-month follow-up (mean 36.3 ± 20.3 months). Treatment success and failure were defined using MSIS Tier-1 criteria. Independent predictors of failure were identified using multivariate logistic regression and Random Forest classification model. Results: Most infections were late in onset (91.6%), and 68.2% were culture-positive. Difficult-to-treat (DTT) organisms were identified in 22.1% of cases and were associated with significantly worse postoperative WOMAC, KSS, and OKS outcomes (all Conclusions: DTT organisms and shorter time from index surgery to infection were independent predictors of failure following two-stage revision for knee PJI. Exploratory machine-learning analysis identified similar predictor patterns and supports the importance of microbiological factors in determining outcomes.