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

Background: Early systemic antibiotics are central to open-fracture care, and administration within 60 minutes is widely used as a quality benchmark. Whether 60 minutes represents a biological threshold for deep infection remains uncertain. Methods: We conducted a PRISMA 2020- and MOOSE-informed systematic review of acute open long-bone fractures in adults. The protocol and amendment history were retrospectively archived on OSF (doi:10.17605/OSF.IO/7J8QN). Injury-to-antibiotic, first-medical-contact, first-hospital-arrival, and receiving-trauma-centre intervals were analysed separately. Exact 60-, 120-, and 180-minute thresholds were prespecified. Deep infection or fracture-related infection assessed at 90 days or longer was prioritised, and adjusted estimates were preferred. Results: Twenty-four records were screened, 18 full reports were assessed, and 16 reports were retained in the evidence map; 13 provided explicitly adult-only data. No threshold-by-clock stratum contained two compatible adjusted estimates. At 60 minutes, adjusted estimates were centred near the null, including an adjusted odds ratio of 1.02 (95% CI 0.39–2.68). One 120-minute study reported an adjusted hazard ratio of 2.40. An exploratory 180-minute synthesis yielded an odds ratio of 1.15 (95% CI 0.58–2.31; I² = 0%) but combined adjusted and crude evidence. A delay beyond 12 hours was associated with fracture-related infection in one adjusted study (adjusted odds ratio 4.92, 95% CI 1.63–16.90). Certainty was very low for all threshold questions. Conclusions: Available evidence does not establish a universal 60-minute biological cutoff. This uncertainty should not be interpreted as evidence that delay is safe; antibiotics should be administered as soon as feasible.