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 |
|