Comparison of Ceftolozane/Tazobactam Infusion Regimens in a Hollow-Fiber Infection Model against Extensively Drug-Resistant Isolates
Montero, María Milagro (Institut Hospital del Mar d'Investigacions Mèdiques)
Domene-Ochoa, Sandra (Institut Hospital del Mar d'Investigacions Mèdiques)
López-Causapé, Carla
López Montesinos, Inmaculada (Institut Hospital del Mar d'Investigacions Mèdiques)
Luque, Sonia (Hospital del Mar (Barcelona, Catalunya))
Sorlí, Luisa (Institut Hospital del Mar d'Investigacions Mèdiques)
Campillo, Núria (Hospital del Mar (Barcelona, Catalunya))
Padilla León, Eduardo
Prim, Núria
Ferrer Alapont, Lorena (Institut Hospital del Mar d'Investigacions Mèdiques)
Grau, Santiago (Hospital del Mar (Barcelona, Catalunya))
Oliver, Antonio
Horcajada, Juan Pablo (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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.
Ajuts:	Ministerio de Economía y Competitividad PI16/00669 Instituto de Salud Carlos III PI17/00251
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Ceftolozane/tazobactam ; Hollow-fiber ; PK/PD ; XDR ; Pseudomonas aeruginosa
Publicat a:	Microbiology Spectrum, Vol. 10 (june 2022) , ISSN 2165-0497

DOI: 10.1128/spectrum.00892-22
PMID: 35695526

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