2026-06-29T02:29:29Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1067532024-07-17T00:02:11Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Carcas, Antonio J. author Sevillano Fernández, David author González Hidalgo, Natalia author Alou Cervera, Luis author Gómez Gil, Rosa author Muñoz, Mario author Llanos, Lucía author Sánchez Villanueva, Rafael J. author Gonzalez Parra, Emilio author Giménez, María José author Aguilar, Lorenzo 2024-07-16T11:43:22Z 2024-07-16T11:43:22Z 2019-12 Carcas AJ, Sevillano D, González N, Alou L, Gómez-Gil R, Muñoz M, Llanos L, Sanchez-Villanueva RJ, Gonzalez-Parra E, Giménez MJ, Aguilar L. Evaluating the optimal time for amikacin administration with respect to haemodialysis using an in vitro pharmacodynamic simulation against epidemic nosocomial OXA-48 producing Klebsiella pneumoniae ST405 strains. J Glob Antimicrob Resist. 2019 Dec;19:241-251 2213-7165 10.1016/j.jgar.2019.05.027 https://hdl.handle.net/20.500.14352/106753 https://doi.org/10.1016/j.jgar.2019.05.027 31176754 https://www.sciencedirect.com/science/article/pii/S2213716519301377?via%3Dihub Objectives: Bacterial viability and enrichment of resistance resulting from three different amikacin administration schedules with respect to haemodialysis (HD) were assessed against three OXA-48-producing Klebsiella pneumoniae isolated during an outbreak in a Spanish hospital. Methods: A previously described two-compartment dynamic system was used. Three possible amikacin administration schedules were simulated: (i) haemodialysis immediately after amikacin infusion (pre-HD); (ii) infusion immediately after haemodialysis (post-HD); and (iii) infusion at 50% interdialytic period. Amikacin standard dose (SD) and double dose (DD) were simulated for each schedule. Values of Cmax/MIC, Cmax/MPC (mutant prevention concentration), AUC0-48h/MIC, AUC0-48h/MPC and %TMSW (percentage of time that the concentration was inside the mutant selection window) were determined with experimental data and were correlated with the area under the bacterial killing curve of the total population and the resistant subpopulation. Results: Both with SD and DD, the pre-HD schedule resulted in increases at 48h in bacterial counts of the total population at the expense of enrichment of pre-existing resistant subpopulations from 12h onwards for all strains. The estimated %TMSW that prevented enrichment of resistant mutants was <61.5%. The AUC0-48h/MPC (with values of ≈40 being associated with countering of increases in resistant subpopulations) was better than the %TMSW as a predictive parameter. Conclusion: This study showed that the longest times concentrations were above the MPC (i.e. highest AUC0-48h/MPC, lowest %TMSW), the lowest enrichment of resistant subpopulations. This implies use of the highest possible amikacin dose (limited by toxicity) and post-HD as the best administration schedule. eng Evaluating the optimal time for amikacin administration with respect to haemodialysis using an in vitro pharmacodynamic simulation against epidemic nosocomial OXA-48 producing Klebsiella pneumoniae ST405 strains journal article 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URL https://docta.ucm.es/bitstreams/fa32f5c9-b324-4613-bed0-4f42dea27630/download File MD5 46d27ab0e4913a5f5d4d5da4f7bf8f97 2796929 application/pdf 2019 J GLOB ANTIMICROB RESISTANCE - Carcas.pdf