2026-04-18T04:28:20Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4713282024-11-04T06:40:39Zcom_2072_98col_2072_378192

Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model Montero, María M. Domene-Ochoa, Sandra López-Causapé, Carla Luque, Sonia Sorlí, Luisa Campillo, Núria Padilla León, Eduardo Prim, Núria Ferrer-Alapont, Lorena Angulo-Brunet, Ariadna Grau, Santiago Oliver, Antonio Horcajada, Juan Pablo Universitat Autònoma de Barcelona Antimicrobials Bacteria 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. 2021 Article https://ddd.uab.cat/record/284377 urn:10.1038/s41598-021-01784-4 urn:oai:ddd.uab.cat:284377 urn:pmcid:PMC8589991 urn:pmc-uid:8589991 urn:pmid:34773066 urn:oai:pubmedcentral.nih.gov:8589991 urn:oai:egreta.uab.cat:publications/b80653b1-0c4e-45d4-8671-a34be37a7f30 http://hdl.handle.net/2072/471328 eng Ministerio de Economía y Competitividad PI16/00669 Instituto de Salud Carlos III PI17/00251 Scientific reports ; Vol. 11 (november 2021) open access 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. https://creativecommons.org/licenses/by/4.0/ application/pdf