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

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 dalbavanc...

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Autores principales: De Nicolò, Amedeo, Stroffolini, Giacomo, Antonucci, Miriam, Mula, Jacopo, De Vivo, Elisa Delia, Cusato, Jessica, Palermiti, Alice, Cariti, Giuseppe, Di Perri, Giovanni, Corcione, Silvia, De Rosa, Francesco Giuseppe, D’Avolio, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533485/
https://www.ncbi.nlm.nih.gov/pubmed/34680409
http://dx.doi.org/10.3390/biomedicines9101288
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author De Nicolò, Amedeo
Stroffolini, Giacomo
Antonucci, Miriam
Mula, Jacopo
De Vivo, Elisa Delia
Cusato, Jessica
Palermiti, Alice
Cariti, Giuseppe
Di Perri, Giovanni
Corcione, Silvia
De Rosa, Francesco Giuseppe
D’Avolio, Antonio
author_facet De Nicolò, Amedeo
Stroffolini, Giacomo
Antonucci, Miriam
Mula, Jacopo
De Vivo, Elisa Delia
Cusato, Jessica
Palermiti, Alice
Cariti, Giuseppe
Di Perri, Giovanni
Corcione, Silvia
De Rosa, Francesco Giuseppe
D’Avolio, Antonio
author_sort De Nicolò, Amedeo
collection PubMed
description 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 AUC(0-2w)/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.
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spelling pubmed-85334852021-10-23 Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context De Nicolò, Amedeo Stroffolini, Giacomo Antonucci, Miriam Mula, Jacopo De Vivo, Elisa Delia Cusato, Jessica Palermiti, Alice Cariti, Giuseppe Di Perri, Giovanni Corcione, Silvia De Rosa, Francesco Giuseppe D’Avolio, Antonio Biomedicines Article 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 AUC(0-2w)/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. MDPI 2021-09-22 /pmc/articles/PMC8533485/ /pubmed/34680409 http://dx.doi.org/10.3390/biomedicines9101288 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
De Nicolò, Amedeo
Stroffolini, Giacomo
Antonucci, Miriam
Mula, Jacopo
De Vivo, Elisa Delia
Cusato, Jessica
Palermiti, Alice
Cariti, Giuseppe
Di Perri, Giovanni
Corcione, Silvia
De Rosa, Francesco Giuseppe
D’Avolio, Antonio
Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context
title Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context
title_full Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context
title_fullStr Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context
title_full_unstemmed Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context
title_short Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context
title_sort long-term pharmacokinetics of dalbavancin in absssi and osteoarticular settings: a real-life outpatient context
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533485/
https://www.ncbi.nlm.nih.gov/pubmed/34680409
http://dx.doi.org/10.3390/biomedicines9101288
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