Evaluating oritavancin for Gram-positive infections: a systematic review of on-label and off-label use

Background: Oritavancin is a long-acting lipoglycopeptide antibiotic approved for acute bacterial skin and skin structure infections (ABSSSI) with potential applicability across difficult-to-treat Gram-positive infections such as osteomyelitis, bacteraemia and endocarditis. This systematic review evaluates the efficacy, safety and clinical use of oritavancin across on-label and off-label indications. Methods: MEDLINE and CENTRAL were searched (2011–2024) for randomized trials, retrospective cohorts, case series and real-world evidence reporting clinical outcomes following oritavancin administration. Risk of bias was assessed using Critical Appraisal Skills Programme (CASP) tools for randomized clinical trials and cohort studies. Results: Twenty-five studies met inclusion criteria: 11 evaluating ABSSSI (n=2311) and 14 assessing off-label use (n=692), including for osteomyelitis, bacteraemia and endocarditis. Across ABSSSI randomized clinical trials, oritavancin demonstrated clinical cure rates of 79.6–83.3%, comparable to those of vancomycin. In retrospective studies, clinical success rates ranged from 85% to 88% in ABSSSI retrospective studies and from 70% to 100% in off-label studies. Adverse events were primarily mild to moderate. Conclusions: Oritavancin is effective for ABSSSI and may be a promising treatment alternative for selected Gram-positive off-label indications requiring prolonged therapy. Standardized dosing strategies and prospective trials are needed to define optimal regimens for off-label indications.