Abstract
PURPOSE: Osteomyelitis continues to pose significant challenges in clinical management, with no universally accepted treatment guidelines at either national or international level as of 2025. Amoxicillin/clavulanic acid (AMC) is a widely used β-lactam antibiotic known for its safety, tolerability, and broad-spectrum activity against common osteomyelitis pathogens. This work seeks to determine whether oral AMC could serve as a viable and effective option in the management of osteomyelitis based on the current treatment landscape of osteomyelitis. METHODS: Preferred Reporting Items for Systematic Reviews (PRISMA) were applied during the preparation of the article. For the structured search in PubMed(®), The Cochrane Library, and UpToDate(®), key research questions were defined and translated into specific search terms. Inclusion and exclusion criteria were defined using the population-intervention-comparison-outcome-study design strategy. All relevant publications available from 1981 to March 2025 were considered. RESULTS: A total of 1,321 publications were identified. After applying in- and exclusion criteria - supported by automation tools - 104 publications were analysed. The number of primary studies specifically investigating AMC for osteomyelitis is limited. However, available data suggest that AMC is effective and demonstrates non-inferiority compared to standard reference antibiotics. Pharmacokinetic data indicate that prolonged and repeated dosing may enhance distribution into deeper compartments, including bone tissue. Reported adverse effects of AMC are generally mild to moderate, in contrast to alternative agents. CONCLUSION: The analysis of the included publications and theoretical considerations on the treatment of osteomyelitis show that surgical debridement followed by long-term administration of AMC can be an effective option for empirical therapy.