López Montesinos, InmaculadaMontero, Maria MilagroDomene Ochoa, SandraLópez-Causapé, CarlaEcheverría Esnal, DanielSorli Redó, M. LuisaCampillo Ambrós, NúriaLuque Pardos, SòniaPadilla, EduardoPrim, NúriaGrau Cerrato, SantiagoOliver, AntonioHorcajada Gallego, Juan Pablo2023-02-212023-02-212022Lopez-Montesinos I, Montero MM, Domene-Ochoa S, López-Causapé C, Echeverria D, Sorlí L, et al. Suboptimal concentrations of ceftazidime/avibactam (CAZ-AVI) may select for CAZ-AVI resistance in extensively drug-resistant pseudomonas aeruginosa. in vivo and In vitro evidence. Antibiotics (Basel). 2022 Oct 22; 11(11): 1456. DOI: 10.3390/antibiotics111114562079-6382http://hdl.handle.net/10230/55832This study correlates in vivo findings in a patient with an extensively drug-resistant (XDR) P. aeruginosa infection who developed resistance to ceftazidime-avibactam (CAZ-AVI) with in vitro results of a 7-day hollow-fiber infection model (HFIM) testing the same bacterial strain. The patient was critically ill with ventilator-associated pneumonia caused by XDR P. aeruginosa ST175 with CAZ-AVI MIC of 6 mg/L and was treated with CAZ-AVI in continuous infusion at doses adjusted for renal function. Plasma concentrations of CAZ-AVI were analyzed on days 3, 7, and 10. In the HIFM, the efficacy of different steady-state concentrations (Css) of CAZ-AVI (12, 18, 30 and 48 mg/L) was evaluated. In both models, a correlation was observed between the decreasing plasma levels of CAZ-AVI and the emergence of resistance. In the HIFM, a Css of 30 and 48 mg/L (corresponding to 5× and 8× MIC) had a bactericidal effect without selecting resistant mutants, whereas a Css of 12 and 18 mg/L (corresponding to 2× and 3× MIC) failed to prevent the emergence of resistance. CAZ/AVI resistance development was caused by the selection of a single ampC mutation in both patient and HFIM. Until further data are available, strategies to achieve plasma CAZ-AVI levels at least 4× MIC could be of interest, particularly in severe and high-inoculum infections caused by XDR P. aeruginosa with high CAZ-AVI MICs.application/pdfengCopyright © 2022 by Lopez-Montesinos I, Montero MM, Domene-Ochoa S, López-Causapé C, Echeverria D, Sorlí L, et al. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/antibiotics11111456PK/PDPseudomonas aeruginosaCeftazidime/avibactamContinuous infusionHollow fiberMultidrug-resistantinfo:eu-repo/semantics/openAccess