2026-04-29T17:03:10Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/235282024-11-28T20:11:47Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967col_20.500.12105_16983

00925njm 22002777a 4500 dc Lopez-Montesinos, Inmaculada author Montero, María Milagro author Domene-Ochoa, Sandra author López-Causapé, Carla author Echeverria, Daniel author Sorli, Luisa author Campillo, Nuria author Luque, Sonia author Padilla, Eduardo author Prim, Nuria author Grau, Santiago author Oliver, Antonio author Horcajada, Juan P author 2022-10-22 This 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. Lopez-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. 10.3390/antibiotics11111456 2079-6382 Antibiotics (Basel, Switzerland) http://hdl.handle.net/20.500.13003/18677 36358110 L2020031559 2-s2.0-85141766255 https://hdl.handle.net/20.500.12105/23528 880681800001 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