Proactive Therapeutic Drug MONiToring to Guide Suppressive Antibiotic Therapy with DALBAvaNcin ( > 12 weeks) in...

Introduction: Long-term dalbavancin use is increasingly adopted off-label for osteoarticular infections (OAIs), but data on administration timing and long-term effects beyond 12 weeks are scarce. This study evaluated the pharmacological efficacy of proactive therapeutic drug monitoring (TDM) to optimize dalbavancin administration. Methods: This single-center, retrospective study included adult OAI patients treated with $\ge 4$ doses of dalbavancin from July 2022 to October 2024. Initial doses were given on days 1, 8, and 43. From the third dose onward, $C_{min}$ and $C_{max}$ values informed dosing schedules via log-linear regression models, targeting $C_{min}\ge 8$ mg L^-1. The primary outcome was the pharmacological efficacy of dalbavancin, assessed by the proportion of patients with $C_{min}\ge 8$ mg L^-1 and $\ge 4$ mg L^-1 after the third dose. Clinical outcomes and safety data were collected as descriptive data. Results: A total of 33 patients provided 118 $C_{min}$ determinations. Pharmacological efficacy was achieved in 93 $/$ 118 (78.8 %) and 114 $/$ 118 (96.6 %) determinations for $C_{min}$ thresholds of $\ge 8$ mg L^-1 and $\ge 4$ mg L^-1, respectively. Efficacy improved when considering only determinations at the correct timing. A total of 18 (54.5 %) patients are still in treatment, while 11 (33.3 %) completed therapy with clinical success. Three patients experienced a relapse after the end of the treatment, while one patient experienced failure, and no adverse events were reported. Conclusions: Dalbavancin is a viable option for prolonged OAI management when other therapies are unavailable or high-risk. Proactive TDM effectively supports this approach by ensuring adequate drug exposure while preventing accumulation.