Comparison of Ceftolozane/Tazobactam Infusion Regimens in a Hollow-Fiber Infection Model against Extensively Drug-Resistant Isolates
Montero, María Milagro ![ORCID Identifier](/img/uab/orcid.ico)
(Institut Hospital del Mar d'Investigacions Mèdiques)
Domene-Ochoa, Sandra ![ORCID Identifier](/img/uab/orcid.ico)
(Institut Hospital del Mar d'Investigacions Mèdiques)
López-Causapé, Carla
López Montesinos, Inmaculada ![ORCID Identifier](/img/uab/orcid.ico)
(Institut Hospital del Mar d'Investigacions Mèdiques)
Luque, Sonia ![ORCID Identifier](/img/uab/orcid.ico)
(Hospital del Mar (Barcelona, Catalunya))
Sorlí, Luisa ![ORCID Identifier](/img/uab/orcid.ico)
(Institut Hospital del Mar d'Investigacions Mèdiques)
Campillo, Núria (Hospital del Mar (Barcelona, Catalunya))
Padilla León, Eduardo
Prim, Núria ![ORCID Identifier](/img/uab/orcid.ico)
Ferrer Alapont, Lorena (Institut Hospital del Mar d'Investigacions Mèdiques)
Grau, Santiago
(Hospital del Mar (Barcelona, Catalunya))
Oliver, Antonio ![ORCID Identifier](/img/uab/orcid.ico)
Horcajada, Juan Pablo
(Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona
Date: |
2022 |
Abstract: |
The aim of this study was to compare the efficacy of intermittent (1-h), extended (4-h), and continuous ceftolozane-tazobactam (C/T) infusion against three extensively drug-resistant (XDR) sequence type (ST) 175 isolates with different susceptibilities to C/T (MIC = 2 to 16 mg/L) in a 7-day hollow-fiber infection model (HFIM). C/T in continuous infusion achieved the largest reduction in total number of bacterial colonies in the overall treatment arms for both C/T-susceptible and -resistant isolates. It was also the only regimen with bactericidal activity against all three isolates. These data suggest that continuous C/T infusion should be considered a potential treatment for infections caused by XDR isolates, including nonsusceptible ones. Proper use of C/T dosing regimens may lead to better clinical management of XDR infections. IMPORTANCE Ceftolozane-tazobactam (C/T) is an antipseudomonal antibiotic with a high clinical impact in treating infection caused by extensively drug-resistant (XDR) isolates, but resistance is emerging. Given its time-dependent behavior, C/T continuous infusion can improve exposure and therefore the pharmacokinetic/pharmacodynamic target attainment. We compared the efficacy of intermittent, extended, and continuous C/T infusion against three XDR ST175 isolates with different C/T MICs by means of an in vitro dynamic hollow-fiber model. We demonstrated that C/T in continuous infusion achieved the largest reduction in bacterial density in the overall treatment arms for both susceptible and resistant isolates. It was also the only regimen with bactericidal activity against all three isolates. Through this study, we want to demonstrate that developing individually tailored antimicrobial treatments is becoming essential. Our results support the role of C/T level monitoring and of dose adjustments for better clinical management and outcomes. |
Grants: |
Ministerio de Economía y Competitividad PI16/00669 Instituto de Salud Carlos III PI17/00251
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Rights: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ![Creative Commons](/img/licenses/by.ico) |
Language: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Subject: |
Ceftolozane/tazobactam ;
Hollow-fiber ;
PK/PD ;
XDR ;
Pseudomonas aeruginosa |
Published in: |
Microbiology Spectrum, Vol. 10 (june 2022) , ISSN 2165-0497 |
DOI: 10.1128/spectrum.00892-22
PMID: 35695526
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Record created 2023-08-08, last modified 2024-01-08