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

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dc.contributor.authorCarcas, Antonio J.
dc.contributor.authorSevillano Fernández, David
dc.contributor.authorGonzález Hidalgo, Natalia
dc.contributor.authorAlou Cervera, Luis
dc.contributor.authorGómez Gil, Rosa
dc.contributor.authorMuñoz, Mario
dc.contributor.authorLlanos, Lucía
dc.contributor.authorSánchez Villanueva, Rafael J.
dc.contributor.authorGonzalez Parra, Emilio
dc.contributor.authorGiménez, María José
dc.contributor.authorAguilar, Lorenzo
dc.date.accessioned2024-07-16T11:43:22Z
dc.date.available2024-07-16T11:43:22Z
dc.date.issued2019-12
dc.descriptionIP13-01530
dc.description.abstractObjectives: 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.
dc.description.departmentDepto. de Medicina
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipMinisterio de Ciencia y Tecnología (España)
dc.description.sponsorshipInstituto de Salud Carlos III (España)
dc.description.statuspub
dc.identifier.citationCarcas 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
dc.identifier.doi10.1016/j.jgar.2019.05.027
dc.identifier.issn2213-7165
dc.identifier.officialurlhttps://doi.org/10.1016/j.jgar.2019.05.027
dc.identifier.pmid31176754
dc.identifier.relatedurlhttps://www.sciencedirect.com/science/article/pii/S2213716519301377?via%3Dihub
dc.identifier.urihttps://hdl.handle.net/20.500.14352/106753
dc.journal.titleJournal of Global Antimicrobial Resistance
dc.language.isoeng
dc.page.final251
dc.page.initial241
dc.publisherElsevier
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCII/IP13/IP13-01530
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/PT12/0002
dc.rights.accessRightsrestricted access
dc.subject.cdu579 Microbiología
dc.subject.keywordAmikacin
dc.subject.keywordCarbapenemase
dc.subject.keywordDialysis
dc.subject.keywordKlebsiella pneumoniae
dc.subject.keywordOXA-48
dc.subject.keywordPharmacodynamics.
dc.subject.ucmMicrobiología médica
dc.subject.unesco2414 Microbiología
dc.titleEvaluating 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
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number19
dspace.entity.typePublication
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relation.isAuthorOfPublication41cae2d7-0146-4705-b653-a302a81db4d0
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relation.isAuthorOfPublication.latestForDiscovery518c916a-df78-48cc-9bf7-6a2aaca7d6a2
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