Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model

Abstract Ceftolozane/tazobactam (C/T) has emerged as a potential agent for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. As it is a time-dependent antimicrobial, prolonged infusion may help achieve pharmacokinetic/pharmacodynamic (PK/PD) targets. To compare alt...

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Autores principales:	María M. Montero, Sandra Domene-Ochoa, Carla López-Causapé, Sonia Luque, Luisa Sorlí, Núria Campillo, Eduardo Padilla, Núria Prim, Lorena Ferrer-Alapont, Ariadna Angulo-Brunet, Santiago Grau, Antonio Oliver, Juan P. Horcajada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76cd59f545be4571a6c2bdb9e115a623
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spelling	oai:doaj.org-article:76cd59f545be4571a6c2bdb9e115a6232021-11-14T12:20:46ZImpact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model10.1038/s41598-021-01784-42045-2322https://doaj.org/article/76cd59f545be4571a6c2bdb9e115a6232021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01784-4https://doaj.org/toc/2045-2322Abstract Ceftolozane/tazobactam (C/T) has emerged as a potential agent for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. As it is a time-dependent antimicrobial, prolonged infusion may help achieve pharmacokinetic/pharmacodynamic (PK/PD) targets. To compare alternative steady-state concentrations (Css) of C/T in continuous infusion (CI) against three XDR P. aeruginosa ST175 isolates with C/T minimum inhibitory concentration (MIC) values of 2 to 16 mg/L in a hollow-fiber infection model (HFIM). Duplicate 10-day HFIM assays were performed to evaluate Css of C/T in CI: one compared 20 and 45 mg/L against the C/T-susceptible isolate while the other compared 45 and 80 mg/L against the two C/T-non-susceptible isolates. C/T resistance emerged when C/T-susceptible isolate was treated with C/T in CI at a Css of 20 mg/L; which showed a deletion in the gene encoding AmpC β-lactamase. The higher dosing regimen (80 mg/L) showed a slight advantage in effectiveness. The higher dosing regimen has the greatest bactericidal effect, regardless of C/T MIC. Exposure to the suboptimal Css of 20 mg/L led to the emergence of C/T resistance in the susceptible isolate. Antimicrobial regimens should be optimized through C/T levels monitoring and dose adjustments to improve clinical management.María M. MonteroSandra Domene-OchoaCarla López-CausapéSonia LuqueLuisa SorlíNúria CampilloEduardo PadillaNúria PrimLorena Ferrer-AlapontAriadna Angulo-BrunetSantiago GrauAntonio OliverJuan P. HorcajadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María M. Montero Sandra Domene-Ochoa Carla López-Causapé Sonia Luque Luisa Sorlí Núria Campillo Eduardo Padilla Núria Prim Lorena Ferrer-Alapont Ariadna Angulo-Brunet Santiago Grau Antonio Oliver Juan P. Horcajada Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
description	Abstract Ceftolozane/tazobactam (C/T) has emerged as a potential agent for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. As it is a time-dependent antimicrobial, prolonged infusion may help achieve pharmacokinetic/pharmacodynamic (PK/PD) targets. To compare alternative steady-state concentrations (Css) of C/T in continuous infusion (CI) against three XDR P. aeruginosa ST175 isolates with C/T minimum inhibitory concentration (MIC) values of 2 to 16 mg/L in a hollow-fiber infection model (HFIM). Duplicate 10-day HFIM assays were performed to evaluate Css of C/T in CI: one compared 20 and 45 mg/L against the C/T-susceptible isolate while the other compared 45 and 80 mg/L against the two C/T-non-susceptible isolates. C/T resistance emerged when C/T-susceptible isolate was treated with C/T in CI at a Css of 20 mg/L; which showed a deletion in the gene encoding AmpC β-lactamase. The higher dosing regimen (80 mg/L) showed a slight advantage in effectiveness. The higher dosing regimen has the greatest bactericidal effect, regardless of C/T MIC. Exposure to the suboptimal Css of 20 mg/L led to the emergence of C/T resistance in the susceptible isolate. Antimicrobial regimens should be optimized through C/T levels monitoring and dose adjustments to improve clinical management.
format	article
author	María M. Montero Sandra Domene-Ochoa Carla López-Causapé Sonia Luque Luisa Sorlí Núria Campillo Eduardo Padilla Núria Prim Lorena Ferrer-Alapont Ariadna Angulo-Brunet Santiago Grau Antonio Oliver Juan P. Horcajada
author_facet	María M. Montero Sandra Domene-Ochoa Carla López-Causapé Sonia Luque Luisa Sorlí Núria Campillo Eduardo Padilla Núria Prim Lorena Ferrer-Alapont Ariadna Angulo-Brunet Santiago Grau Antonio Oliver Juan P. Horcajada
author_sort	María M. Montero
title	Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
title_short	Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
title_full	Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
title_fullStr	Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
title_full_unstemmed	Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
title_sort	impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant pseudomonas aeruginosa isolates in a hollow-fiber infection model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/76cd59f545be4571a6c2bdb9e115a623
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Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model

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