Short-course versus long-course antibiotics in bone infections: a meta-analysis of randomised controlled trials

Purpose The optimal duration of antibiotic therapy for bone infections remains controversial. We therefore conducted a meta-analysis of randomised controlled trials (RCTs) comparing short- versus long-course antibiotic therapy for bone infections. Methods PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched through February 2026 for RCTs comparing short- and long-course antibiotic therapy in bone infections, including periprosthetic joint infection, diabetic foot osteomyelitis, vertebral osteomyelitis, and paediatric acute haematogenous osteomyelitis. Treatment failure and antibiotic-related adverse events were analysed using both intention-to-treat (ITT) and per-protocol (PP) data. Risk of bias and certainty of evidence were assessed using ROB 1 and GRADE. Results In the ITT analysis, no significant difference in treatment failure was observed between short- and long-course therapy (RR = 1.12, 95% CI 0.77–1.62, P = 0.55). The PP analysis suggested a potential increase in treatment failure with short-course therapy (RR = 1.47, 95% CI 1.00–2.16, P = 0.05). Short-course therapy was associated with a significantly lower risk of antibiotic-related adverse events (RR = 0.81, 95% CI 0.69–0.94, P = 0.006). Certainty of evidence was moderate for treatment failure outcomes and high for adverse events. Conclusion No statistically significant difference in treatment failure was observed between short- and long-course antibiotic therapy in the ITT analysis, whereas short-course therapy was associated with significantly fewer antibiotic-related adverse events. However, the PP analysis suggested a possible increase in treatment failure with short-course therapy. The included bone infections were clinically heterogeneous, which may limit generalisability.