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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  • dc.contributor.author Montero, Maria Milagro
  • dc.contributor.author Domene Ochoa, Sandra
  • dc.contributor.author López-Causapé, Carla
  • dc.contributor.author Luque Pardos, Sònia
  • dc.contributor.author Sorlí, Luisa
  • dc.contributor.author Campillo Ambrós, Núria
  • dc.contributor.author Padilla, Eduardo
  • dc.contributor.author Prim, Núria
  • dc.contributor.author Ferrer Alapont, Lorena
  • dc.contributor.author Angulo-Brunet, Ariadna
  • dc.contributor.author Grau Cerrato, Santiago
  • dc.contributor.author Oliver, Antonio
  • dc.contributor.author Horcajada Gallego, Juan Pablo
  • dc.date.accessioned 2023-02-14T07:05:24Z
  • dc.date.available 2023-02-14T07:05:24Z
  • dc.date.issued 2021
  • dc.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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Montero MM, Domene-Ochoa S, López-Causapé C, Luque S, Sorlí L, Campillo N, Padilla E, Prim N, Ferrer-Alapont L, Angulo-Brunet A, Grau S, Oliver A, Horcajada JP. Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model. Sci Rep. 2021 Nov 12;11(1):22178. DOI: 10.1038/s41598-021-01784-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-01784-4
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/55756
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Sci Rep. 2021 Nov 12;11(1):22178
  • dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Antimicrobials
  • dc.subject.keyword Bacteria
  • dc.title Impact of ceftolozane/tazobactam concentrations in continuous infusion against extensively drug-resistant Pseudomonas aeruginosa isolates in a hollow-fiber infection model
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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