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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/40993
Title: Comparative pharmacodynamics of four different carbapenems in combination with polymyxin B against carbapenem-resistant Acinetobacter baumannii
Authors: Justin R. Lenhard
Jonathan S. Gall
Jurgen B. Bulitta
Visanu Thamlikitkul
Cornelia B. Landersdorfer
Alan Forrest
Roger L. Nation
Jian Li
Brian T. Tsuji
University at Buffalo, State University of New York
California Northstate University College of Pharmacy
University of Florida
Mahidol University
Monash University
The University of North Carolina at Chapel Hill
Keywords: Medicine
Issue Date: 1-Dec-2016
Citation: International Journal of Antimicrobial Agents. Vol.48, No.6 (2016), 719-724
Abstract: © 2016 The objective of this study was to determine the comparative pharmacodynamics of four different carbapenems in combination with polymyxin B (PMB) against carbapenem-resistant Acinetobacter baumannii isolates using time–kill experiments at two different inocula. Two A. baumannii strains (03-149-1 and N16870) with carbapenem minimum inhibitory concentrations (MICs) ranging from 8 to 64 mg/L were investigated in 48-h time–kill experiments using starting inocula of 106 CFU/mL and 108 CFU/mL. Concentration arrays of ertapenem, doripenem, meropenem and imipenem at 0.25×, 0.5×, 1×, 1.5× and 2× published maximum serum concentration (Cmax) values (Cmaxconcentrations of 12, 21, 48 and 60 mg/L, respectively) were investigated in the presence of 1.5 mg/L PMB. Use of carbapenems without PMB resulted in drastic re-growth. All carbapenem combinations were able to achieve a ≥3 log10CFU/mL reduction by 4 h against both strains at 106 CFU/mL, whereas maximum reductions against strain 03-149-1 at 108 CFU/mL were 1.0, 3.2, 2.2 and 3.3 log10CFU/mL for ertapenem, doripenem, meropenem and imipenem, respectively. None of the combinations were capable of reducing 108 CFU/mL of N16870 by ≥2 log10CFU/mL. Ertapenem combinations consistently displayed the least activity, whereas doripenem, meropenem and imipenem combinations had similar activities that were poorly predicted by carbapenem MICs. As doripenem, meropenem, or imipenem displayed similar pharmacodyanmics in combination, the decision of which carbapenem to use in combination with PMB may be based on toxicodynamic profiles if drastic discordance in MICs is not present.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85001052610&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/40993
ISSN: 18727913
09248579
Appears in Collections:Scopus 2016-2017

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