Abstract
Background: Dalbavancin and oritavancin are long-acting lipoglycopeptides increasingly used off-label for a variety of Gram-positive infections. While their efficacy has been described in osteomyelitis, bacteremia, and infective endocarditis, evidence specifically addressing cardiovascular prosthetic infections such as prosthetic valve endocarditis (PVE), cardiac implantable electronic device (CIED) infections, left ventricular assist device infections (LVAD), and prosthetic vascular graft infections (PVGI) remains limited. These conditions are particularly challenging due to biofilm formation, difficulties in achieving surgical source control, and the frequent need for prolonged or suppressive therapy. Objectives: This systematic review aimed to summarize the available literature on the use of dalbavancin and oritavancin in cardiovascular prosthetic infections, with a focus on therapeutic strategies, clinical outcomes, and safety. Methods: We performed a systematic search of PubMed, Embase, Scopus, and Cochrane Library up to 24 June 2025 in accordance with PRISMA guidelines. Eligible studies included adults treated with dalbavancin or oritavancin for cardiovascular prosthetic infections. Data on study characteristics, population demographics, causative pathogens, and microbiological profiles, antibiotic regimens, treatment duration, use of therapeutic drug monitoring (TDM), indication or non-indication for chronic suppressive therapy, adverse events, clinical outcomes, and clinical efficacy were extracted. Results: Twenty studies comprising 113 patients were identified, of whom 111 received dalbavancin and 2 oritavancin. The main infections were PVE, CIED, LVAD, and PVGI. Dalbavancin was most effective as consolidation therapy after surgery or device removal, with high cure rates. Prolonged regimens were used as bridging or in partially treated cases, sometimes supported by TDM or PET/CT. Chronic suppressive therapy, mainly for LVAD and PVGI infections, achieved variable outcomes with relapses in about one fifth of patients. Adverse events were infrequent and generally mild. Conclusions: The included studies were highly diverse, conducted in various settings and with different objectives. Eight of the twenty included studies were single case reports on dalbavancin and oritavancin, highlighting the predominance of individual case descriptions in the available literature. Long-acting lipoglycopeptides may represent a valuable option for cardiovascular prosthetic infections. Their role appears most favorable as consolidation after adequate source control, while chronic suppressive use showed heterogeneous outcomes. This systematic review was registered on Open Science Framework. This work was supported by grants from the Italian Ministry of Health through Ricerca Corrente, Linea 3, Progetto 3.