Pathogen-Specific Risk for Iterative Surgical Debridement in Orthopedic Infections: A Prospective Multicohort Analysis

Background/Objectives: Almost all orthopedic infections require a combination of surgi-cal debridement with targeted antimicrobial treatment. The number of debridement may vary considerably between infection episodes. The case-mix is enormous and so-called "second looks" are frequent. We investigate which bacteria are associated with second looks to achieve local infection control. Methods: We used a composite database stem-ming from three prospective randomized-controlled trials (RCTs) 2019-2025 with proto-colled surgical debridement (initial debridement). In these RCTs, we allowed additional debridement only in case of persistent (during several days) or progredient local infection. Results: Overall, 201/1,067 (18.8%) orthopedic infections required multiple debridement (median two second looks, range 2–8 surgeries). Gram-negative pathogens revealed the highest risk for "second looks" (28.2%), followed by implant-related infections (25.4%). Cutibacteria yielded the lowest risk (11.7%). In the multivariable logistic regression model, Gram-negative infections (odds ratio 2.04, 95%CI 1.20-3.47) and infected implants (OR 2.18, 95%CI 1.56-3.03) were independently associated to multiple interventions, in con-trast to Staphylococcus aureus, enterococci or streptococci. Conclusions: When analyzing orthopedic infections included in prospective RCTs, Gram-negative pathogens groups significantly associate with the need for second looks, which matches our own experience. Today findings support preoperative counseling, antibiotic stewardship, and operative planning for a staged management in infection cases with a high risk of clinical failure. Trials registrations: NCT04048304, NCT04081792, NCT05499481.