Montero, Maria MDomene-Ochoa, SandraLópez-Causapé, CarlaLuque, SoniaSorli, LuisaCampillo, NuriaPadilla, EduardoPrim, NuriaFerrer-Alapont, LorenaAngulo-Brunet, AriadnaGrau, SantiagoOliver, AntonioHorcajada, Juan P2024-09-182024-09-182021-11-12Montero MM, Domene-Ochoa S, Lopez-Causape C, Luque S, Sorli L, Campillo N, et al. 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):22178.2045-2322https://hdl.handle.net/20.500.13003/19634https://hdl.handle.net/20.500.12105/23320Ceftolozane/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 beta-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.enghttp://creativecommons.org/licenses/by/4.0/Dose-Response Relationship, DrugDrug Resistance, Multiple, BacterialAnti-Bacterial AgentsIn Vitro TechniquesMicrobial Sensitivity TestsHumansCephalosporinsPseudomonas aeruginosaTazobactamPseudomonas Infectionsresearch articleAttribution 4.0 International347730661112217810.1038/s41598-021-01784-4Scientific Reportsopen accessPruebas de Sensibilidad MicrobianaFarmacorresistencia Bacteriana MúltipleRelación Dosis-Respuesta a DrogaHumanosCefalosporinasTazobactamInfecciones por PseudomonasTécnicas In VitroPseudomonas aeruginosaAntibacterianos2-s2.0-85118981864718023200023L636737081