Saving Beds and Budgets: Real-World Efficacy, Safety, and Pharmacoeconomics of Long-Acting Lipoglycopeptides (LALs) in a Day Hospital Setting

Background: Long-acting lipoglycopeptides (LALs), including dalbavancin and oritavancin, may facilitate outpatient-oriented management of Gram-positive infections by reducing the need for prolonged hospitalization and daily intravenous therapy. However, real-world evidence on their use in day hospital pathways, particularly for complex off-label infections, remains limited. This study evaluated the clinical effectiveness, safety, and economic impact of LAL-based day hospital management, comparing in-label acute bacterial skin and skin-structure infections (ABSSSI) with complex off-label indications. Methods: This retrospective, multicenter observational study included 160 adult patients treated with dalbavancin and/or oritavancin in a day hospital setting across nine Italian centers between January 2020 and December 2025. Indications were classified as in-label ABSSSI or off-label infections, including osteomyelitis, prosthetic joint infection, spondylodiscitis, endocarditis, septic arthritis, and prosthetic cardiac infection. The primary endpoint was clinical success at final follow-up. Secondary endpoints included adverse drug events, readmissions, inflammatory marker response, and a budget impact cost-offset analysis based on avoided inpatient bed-days. Results: Overall, 54.4% of patients received LALs for off-label indications, mainly osteomyelitis, prosthetic joint infection, and spondylodiscitis. Clinical outcome was available for 159 patients, with an overall success rate of 86.8% (138/159). Success rates were 90.4% for in-label ABSSSI and 83.7% for off-label indications, with no statistically significant difference between groups (p = 0.247). In exploratory analyses, monotherapy was associated with lower failure odds; this most likely reflects confounding by indication and should not be interpreted as a treatment effect. Inflammatory markers significantly decreased from baseline to end of therapy. Adverse drug events were uncommon (3.3%), mild, and did not lead to treatment discontinuation. In a scenario-based cost-offset model (no matched inpatient comparator), the strategy corresponded to 1107–2214 avoided inpatient bed-days; estimated net savings ranged from approximate cost-neutrality under conservative assumptions (€11,976) to €676,176 under maximum assumptions, and one-way sensitivity analysis showed a possible net loss at low inpatient daily-cost values—underscoring that these are modeled rather than observed savings. Conclusions: In this uncontrolled, retrospective cohort, LAL-based day hospital management was feasible and associated with favorable observed clinical outcomes, an acceptable safety profile, and a potential for cost offset in selected patients with Gram-positive infections, including complex off-label indications. Because no matched inpatient or conventional OPAT comparator was included, these findings should be regarded as hypothesis-generating and cannot establish comparative efficacy, superiority, or actual cost savings.