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

Abstract

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.

Figure 1

Clinical practice in OPAT service applying a TDM-based method to plan dalbavancin administrations for a duration of treatment longer than 12 weeks. Created in https://BioRender.com (last access: 5 May 2025).

Figure 2

Patient inclusion flowchart.

Figure 3

The left panel represents the interval between dalbavancin administrations in days (after excluding the first three doses). The number in parentheses indicates the number of dalbavancin administrations received by each patient. The right panel represents the same interval after excluding the administrations beyond 7 d from the suggested date (note the difference in patients ID_14 and ID_16).