Oritavancin for Treatment of Osteomyelitis: A Systematic Review and Meta‐Analysis of Observational Studies

Background Osteomyelitis (OM) is a complex inflammatory bone infection typically requiring prolonged antibiotic therapy. Oritavancin (ORI), a long‐acting lipoglycopeptide with activity against biofilm‐embedded pathogens, has emerged as a potential treatment option despite previous US Food and Drug Administration (FDA) warnings against its use in OM. Methods We conducted a systematic review and meta‐analysis of observational studies in seven databases through August 8, 2024 (PROSPERO registration: CRD42025635473) to evaluate the available evidence on ORI's efficacy and safety in OM. Clinical success was defined as the improvement or resolution of infection without requiring additional gram‐positive antibiotics, surgical debridement, or amputation. Study quality was assessed using the Newcastle–Ottawa Scale. Results Our systematic review included nine observational studies comprising 316 patients with OM treated with ORI. Quality assessment using the Newcastle‐Ottawa Scale revealed scores ranging from 5/9 to 8/9, with most studies demonstrating adequate outcome assessment but limitations in cohort selection and comparability. Meta‐analysis demonstrated a pooled clinical success rate of 81% (95% CI: 76%–85%). Comparative analysis of two studies yielded an odds ratio of 2.99 (95% CI: 0.86–10.36) favoring ORI over comparators (daptomycin and dalbavancin), though with substantial heterogeneity ( I 2 = 80.2%, p = 0.0247). Conclusions Despite previous warnings, we found no evidence of ineffectiveness with ORI for OM. ORI's infrequent dosing schedule may provide convenience over daily parenteral therapy, particularly for difficult‐to‐treat pathogens like MRSA and VRE. Further research is needed to optimize dosing strategies based on pathogen susceptibility and establish appropriate therapeutic drug monitoring protocols.