Oritavancin for Gram-Positive Bone and Joint Infections: A Comprehensive Review of the Literature

<b>Background:</b> Bone and joint infections (BJIs), including osteomyelitis, septic arthritis, and periprosthetic joint infections, typically require prolonged antimicrobial therapy and often involve complex outpatient management. Oritavancin, a long-acting lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria, has emerged as a potential off-label option for BJIs owing to its favourable pharmacokinetic and pharmacodynamic properties. <b>Objectives:</b> To provide a comprehensive overview of the pharmacological rationale, microbiological activity, and available clinical evidence supporting the use of oritavancin in BJIs. <b>Methods:</b> A comprehensive narrative review of the literature was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL), focusing on publications from 2011 to 2025. Observational studies, case series, and case reports describing the off-label use of oritavancin in BJIs were considered. <b>Results:</b> The available literature primarily consists of observational studies and real-world experiences. Eighteen studies met the inclusion criteria. Oritavancin was most frequently evaluated for osteomyelitis (n = 14 studies), prosthetic joint infections (n = 10) and septic arthritis (n = 5). Multi-dose regimens, typically including a 1200 mg loading dose followed by weekly doses of 800-1200 mg, were the most commonly described strategies. Reported clinical success rates generally ranged from approximately 70% to over 90%. Oritavancin was overall well tolerated, with adverse events being mostly mild and self-limiting. <b>Conclusions:</b> Current evidence suggests that oritavancin may represent an effective and well-tolerated off-label option for selected patients with Gram-positive BJIs. Its use may offer practical advantages, including reduced hospitalization and avoidance of prolonged intravenous antimicrobial therapy, particularly in patients for whom standard treatment approaches are challenging.