Universidad Peruana Cayetano Heredia

Optimizing aminoglycoside selection for KPC-producing Klebsiella pneumoniae with the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib

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dc.contributor.author Butler, David A.
dc.contributor.author Rana, Amisha P.
dc.contributor.author Krapp, Fiorella
dc.contributor.author Patel, Shitalben R.
dc.contributor.author Huang, Yanqin
dc.contributor.author Ozer, Egon A.
dc.contributor.author Hauser, Alan R.
dc.contributor.author Bulman, Zackery P.
dc.date.accessioned 2021-04-13T20:51:01Z
dc.date.available 2021-04-13T20:51:01Z
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/20.500.12866/9174
dc.description.abstract OBJECTIVES: KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates commonly co-harbour the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib, which encodes an AME that can confer resistance to some of the commercially available aminoglycosides. We sought to determine the influence of AAC(6')-Ib in KPC-Kp on the pharmacodynamic activity of aminoglycosides. METHODS: Six KPC-Kp clinical isolates, three with and three without aac(6')-Ib, were analysed. Using these isolates, the bacterial killing of amikacin, gentamicin and tobramycin was assessed in static time-kill experiments. The pharmacodynamic activity of the aminoglycosides was then assessed in a dynamic one-compartment infection model over 72 h using simulated human pharmacokinetics of once-daily dosing with amikacin (15 mg/kg), gentamicin (5 mg/kg) and tobramycin (5 mg/kg). RESULTS: At clinically relevant aminoglycoside concentrations in time-kill experiments and the dynamic one-compartment model, gentamicin was more active than amikacin or tobramycin against the isolates harbouring aac(6')-Ib. Amikacin, gentamicin and tobramycin all showed progressively reduced bacterial killing with exposure to repeated doses against most isolates in the dynamic one-compartment model. MIC values were generally not a good predictor of gentamicin pharmacodynamic activity against KPC-Kp, but were more reliable for amikacin and tobramycin. CONCLUSIONS: Gentamicin may be preferred over amikacin or tobramycin for treatment of KPC-Kp infections. However, gentamicin MICs are not a consistent predictor of its pharmacodynamic activity and unexpected treatment failures are possible. en_US
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartofseries Journal of Antimicrobial Chemotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Gentamicin sulfate (usp) en_US
dc.subject amikacin en_US
dc.subject genes en_US
dc.subject gentamicins en_US
dc.subject klebsiella en_US
dc.subject pneumoniae en_US
dc.subject infections en_US
dc.subject enzymes en_US
dc.subject tobramycin en_US
dc.subject pharmacodynamics en_US
dc.subject aminoglycosides en_US
dc.subject killing en_US
dc.subject malnutrition-inflammation-cachexia syndrome en_US
dc.subject augmentative and alternative communication. en_US
dc.title Optimizing aminoglycoside selection for KPC-producing Klebsiella pneumoniae with the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1093/jac/dkaa480
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 1460-2091


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