Lopez-Montesinos, InmaculadaMontero, María MilagroDomene-Ochoa, SandraLópez-Causapé, CarlaEcheverria, DanielSorli, LuisaCampillo, NuriaLuque, SoniaPadilla, EduardoPrim, NuriaGrau, SantiagoOliver, AntonioHorcajada, Juan P2024-10-042024-10-042022-10-22Lopez-Montesinos, I., Montero, M. M., Domene-Ochoa, S., López-Causapé, C., Echeverria, D., Sorlí, L., Campillo, N., Luque, S., Padilla, E., Prim, N., Grau, S., Oliver, A., & Horcajada, J. P. (2022). 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, 11(11), 1456.2079-6382http://hdl.handle.net/20.500.13003/18677https://hdl.handle.net/20.500.12105/23528This 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.enghttp://creativecommons.org/licenses/by/4.0/research articleAttribution 4.0 International36358110111110.3390/antibiotics11111456Antibiotics (Basel, Switzerland)open access2-s2.0-85141766255880681800001L2020031559