Abstract
AIMS: The optimal duration of antibiotic therapy in joint infection remains controversial, particularly as native joint septic arthritis and periprosthetic joint infection (PJI) differ substantially in pathophysiology, surgical management, and prognosis. While short antibiotic courses have been advocated for native joints after adequate drainage, prolonged therapy is often recommended for PJIs due to biofilm-related infection. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to compare short- with long-course antibiotic strategies in both native and prosthetic joint infections. METHODS: Following PRISMA guidelines, a systematic search was performed across PubMed, Embase, Web of Science, and the Cochrane Library. Only RCTs were included. Studies were assessed for inclusion using predefined population, intervention, comparison, outcomes, and study (PICOS) criteria. Meta-analyses were conducted using MedCalc, and treatment failures were analyzed using odds ratios (ORs) with 95% CIs. RESULTS: A total of 12 RCTs involving 1,414 patients (native 577; periprosthetic 837) were included, with six eligible for meta-analysis. For PJIs, long-course therapy (≥ 12 weeks) significantly reduced treatment failure compared with short courses (OR 2.04, 95% CI 1.18 to 3.54; p = 0.011), while complication and mortality rates were similar. In contrast, for native joints, short-course therapy (≤ four weeks) achieved comparable infection control with prolonged regimens (OR 1.347; p = 0.565) when combined with adequate surgical drainage, particularly in paediatric populations. Surgical strategy (e.g. debridement, antibiotics, and implant retention vs one- or two-stage exchange) influenced outcomes more than antibiotic duration alone. CONCLUSION: Optimal antibiotic duration should be individualized based on joint type and surgical approach. Short courses are effective for native septic arthritis with proper drainage, whereas PJIs generally require extended therapy due to biofilm-related complexity. We propose the Age-Joint-Immunity-Surgery-Sensitivity (AJISS) score as a decision-making tool to guide treatment duration, warranting prospective validation.