Timing of First Systemic Antibiotic Administration and Risk of Deep Infection in Adults with Open Long-Bone Fractures: A Systematic Review and Threshold-Specific Evidence Synthesis

Background/Objectives: Early systemic antibiotics are central to open-fracture care, but a 60 min operational target does not establish a biological infection threshold. We examined how time origin, cutoff, and outcome definition affect interpretation of reported associations. Methods: Evidence was reconstructed from two preserved bibliographic inventories containing 24 entries. Complete database-search exports were unavailable, and selection, extraction, ROBINS-E, and GRADE were not independently duplicated. The protocol was archived retrospectively on OSF (doi:10.17605/OSF.IO/7J8QN). Estimates were described separately by time origin, cutoff, adjustment, outcome, and follow-up for a target population aged at least 18 years. No pooled estimate was retained. Results: The historical evidence map contained 16 reports, including contextual reports that did not establish applicability to the target population. This is not a verified final included-study count. Within the preserved inventory, no threshold-by-time-origin group supplied two compatible adjusted estimates. A 191-patient cohort reported an adjusted odds ratio of 1.02 (95% CI 0.39–2.68) at 60 min after emergency-department arrival. Recorded appraisals indicated predominantly high or very high risk of bias and very low certainty; these judgements were not independently verified. Conclusions: Distinguishing care-process targets from causal thresholds improves interpretation of the available reports. However, incomplete searching and single-investigator assessment limit the reliability and completeness of this synthesis. The observational associations establish neither causal thresholds nor the safety of delay and do not justify postponing indicated prophylaxis.