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Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context

Authors :
Amedeo De Nicolò
Giacomo Stroffolini
Miriam Antonucci
Jacopo Mula
Elisa Delia De Vivo
Jessica Cusato
Alice Palermiti
Giuseppe Cariti
Giovanni Di Perri
Silvia Corcione
Francesco Giuseppe De Rosa
Antonio D’Avolio
Source :
Biomedicines, Vol 9, Iss 10, p 1288 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Dalbavancin is a lipoglycopeptide approved for treatment of Gram-positive infections of skin and skin-associated structures (ABSSSI). Currently, off-label use at high dosages for osteoarticular infections deserves attention. This work aimed to study the long-term plasma pharmacokinetics of dalbavancin in outpatients with ABSSSI or osteoarticular infections, treated either with one or two 1500 mg doses of dalbavancin. A liquid chromatography-tandem mass spectrometry method was used to measure total dalbavancin concentrations in plasma samples. The results were analyzed through a non-compartmental analysis (NCA). Breakpoint minimum inhibitory concentration (MIC) was used to calculate AUC/MIC and T > MIC parameters, adjusted by 93% protein binding. A total of 14 patients were enrolled, 11 with osteoarticular infection and 3 with ABSSSI. Long-term pharmacokinetics showed median T > MIC (0.125 mg/L) of 11.9 and 13.7 weeks for single and dual dose, respectively. Similarly, median AUC0-2w/MIC ratios of 20,590 and 31,366 were observed for single and dual dose regimens, respectively. No adverse events were observed, and treatment success was achieved in 12/14 patients. Failure was associated with the worst clinical conditions, bone infections, and single dose. The results of this study show that dalbavancin exposure exceeds previously suggested pharmacodynamic targets. Optimization of these targets is needed for the osteoarticular setting.

Details

Language :
English
ISSN :
22279059
Volume :
9
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.6ab2506c871541768806c58e6f7c54f0
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines9101288