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oai:repisalud.isciii.es:20.500.12105/234042024-11-28T20:09:34Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967col_20.500.12105_16983

00925njm 22002777a 4500 dc Montero, María Milagro author Domene-Ochoa, Sandra author López-Causapé, Carla author López-Montesinos, Inmaculada author Luque, Sonia author Sorlí, Luisa author Campillo, Núria author Padilla, Eduardo author Prim, Núria author Ferrer Alapont, Lorena author Grau, Santiago author Oliver, Antonio author Horcajada, Juan P author 2022 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 P. aeruginosa 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 P. aeruginosa isolates, including nonsusceptible ones. Proper use of C/T dosing regimens may lead to better clinical management of XDR P. aeruginosa infections. IMPORTANCE: Ceftolozane-tazobactam (C/T) is an antipseudomonal antibiotic with a high clinical impact in treating infection caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa 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 P. aeruginosa 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. Montero MM, Domene-Ochoa S, López-Causapé C, López-Montesinos I, Luque S, Sorlí L, et al. Comparison of Ceftolozane/Tazobactam Infusion Regimens in a Hollow-Fiber Infection Model against Extensively Drug-Resistant Pseudomonas aeruginosa Isolates. Ferran AA, editor. Microbiol Spectr. 2022 Jun 29;10(3). 10.1128/spectrum.00892-22 2165-0497 Microbiology spectrum http://hdl.handle.net/20.500.13003/18114 35695526 L2019045522 2-s2.0-85133214250 https://hdl.handle.net/20.500.12105/23404 811807500001 Comparison of Ceftolozane/Tazobactam Infusion Regimens in a Hollow-Fiber Infection Model against Extensively Drug-Resistant Pseudomonas aeruginosa Isolates