Dalbavancin in the Real-World Management of Gram-Positive Infections: A Systematic Review of Randomized and Observational Studies

Gram-positive infections are associated with significant morbidity and healthcare burden, often requiring prolonged intravenous therapy. Dalbavancin, a long-acting lipoglycopeptide, has emerged as a promising option beyond its approved indication for acute bacterial skin and skin structure infections (ABSSSI). A systematic review was conducted according to the PRISMA guidelines (PROSPERO: CRD420261296328). MEDLINE, Embase, CENTRAL, and Web of Science were searched from inception. Randomized controlled trials (RCTs) and observational studies evaluating dalbavancin in adult patients with Gram-positive infections were included. Outcomes of interest were clinical effectiveness, safety, and healthcare resource utilization. Risk of Bias was assessed using RoB 2 and the Newcastle–Ottawa Scale. Twenty-one studies were included. Randomized trials confirmed non-inferior efficacy of dalbavancin compared with standard therapy in ABSSSI. Observational studies demonstrated high clinical success rates across a range of infections, including osteo-articular infections, bloodstream infections, and infective endocarditis (IE), particularly in acute settings. Lower effectiveness was observed in biofilm-related infections without adequate source control. Dalbavancin was frequently used as sequential or consolidation therapy in complex patients. Its use was consistently associated with reduced length of hospital stay, facilitation of outpatient management, and potential cost savings. The safety profile was favorable, including in prolonged or multi-dose regimens. In conclusion, dalbavancin represents an effective and well-tolerated option for Gram-positive infections, with expanding evidence supporting its use in complex and off-label settings. Its pharmacokinetic profile enables simplified treatment strategies and improved healthcare resource utilization, although appropriate patient selection and source control remain essential.