Beyond Surgical Strategy: Host Status and Timing Drive Early Failure in Fracture-Related Infection. Preliminary Results From the Esgiai-Escmid Frimal Pilot Study

Background Fracture-related infection (FRI) requires complex multidisciplinary management, yet determinants of early failure after the first surgical intervention remain poorly defined. Current paradigms prioritise surgical strategy (DAIR vs implant removal), but robust multicentre data challenging this assumption are scarce. We present preliminary results from the FRIMAL study, an ESGIAI-ESCMID initiative, aimed at redefining prognostic drivers in FRI. Methods This retrospective multicentre pilot study included adults with FRI in long-bone fractures diagnosed within 12 weeks after fixation (international consensus definition) across 16 centres in 8 countries (Europe and Africa) between January 2021 and June 2024. Initial management consisted of debridement, antibiotics, and implant retention (DAIR) or implant removal (IR). The primary endpoint was failure after the first surgical procedure. Secondary endpoints included clinical cure, fracture consolidation, and functional recovery at one year. Multivariable logistic regression adjusted for centre identified independent predictors of failure. Results A total of 281 patients were included (median age 59 years; 43.8% female), with DAIR performed in 60.1%. Failure after the first procedure occurred in 33.1%. At one year, 84.7% achieved clinical cure and 78.6% fracture consolidation; however, functional recovery remained limited (55.5%), with persistent pain in 22.4%. Notably, only 46.3% of patients achieved full recovery when all four dimensions of healing (infection control, fracture consolidation, functional recovery, and absence of pain) were fulfilled. Early failure was not primarily driven by surgical strategy. Independent predictors were the need for soft-tissue coverage (OR 2.5; 95% CI 1.1–6.2), hypoalbuminemia (OR 2.6; 95% CI 1.4–4.8), and early timing of surgery (<1 month) (OR 3.4; 95% CI 1.8–6.3). Microbiological complexity and DAIR were associated with failure in univariate analyses. Stratified analyses highlighted timing as a key effect modifier: delayed DAIR increased failure risk, whereas late implant removal and procedures requiring soft-tissue reconstruction were also associated with poorer outcomes. Conclusions In this preliminary international cohort from the FRIMAL pilot study, nearly one-third of patients failed the initial surgical strategy for FRI. These findings challenge the emphasis on surgical technique alone, demonstrating that host status and local tissue conditions are the principal drivers of early failure, with timing as a key modifier. Limitations include the retrospective design and potential centre-level heterogeneity that may outweigh country-level differences. Ongoing data monitoring and validation in the full FRIMAL cohort are required to confirm these findings and strengthen their generalisability.