Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106392
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Type: Journal article
Title: Predictability of phenotype in relation to common β-lactam resistance mechanisms in Escherichia coli and Klebsiella pneumoniae
Other Titles: Predictability of phenotype in relation to common beta-lactam resistance mechanisms in Escherichia coli and Klebsiella pneumoniae
Author: Agyekum, A.
Fajardo-Lubián, A.
Ai, X.
Ginn, A.
Zong, Z.
Guo, X.
Turnidge, J.
Partridge, S.
Iredell, J.
Citation: Journal of Clinical Microbiology, 2016; 54(5):1243-1250
Publisher: American Society for Microbiology
Issue Date: 2016
ISSN: 0095-1137
1098-660X
Statement of
Responsibility: 
Alex Agyekum, Alicia Fajardo-Lubián, Xiaoman Ai, Andrew N. Ginn, Zhiyong Zong, Xuejun Guo, John Turnidge, Sally R. Partridge, Jonathan R. Iredell
Abstract: The minimal concentration of antibiotic required to inhibit the growth of different isolates of a given species with no acquired resistance mechanisms has a normal distribution. We have previously shown that the presence or absence of transmissible antibiotic resistance genes has excellent predictive power for phenotype. In this study, we analyzed the distribution of six β-lactam antibiotic susceptibility phenotypes associated with commonly acquired resistance genes in Enterobacteriaceae in Sydney, Australia. Escherichia coli (n = 200) and Klebsiella pneumoniae (n = 178) clinical isolates, with relevant transmissible resistance genes (blaTEM, n = 33; plasmid AmpC, n = 69; extended-spectrum β-lactamase [ESBL], n = 116; and carbapenemase, n = 100), were characterized. A group of 60 isolates with no phenotypic resistance to any antibiotics tested and carrying none of the important β-lactamase genes served as comparators. The MICs for all drug-bacterium combinations had a normal distribution, varying only in the presence of additional genes relevant to the phenotype or, for ertapenem resistance in K. pneumoniae, with a loss or change in the outer membrane porin protein OmpK36. We demonstrated mutations in ompK36 or absence of OmpK36 in all isolates in which reduced susceptibility to ertapenem (MIC, >1 mg/liter) was evident. Ertapenem nonsusceptibility in K. pneumoniae was most common in the context of an OmpK36 variant with an ESBL or AmpC gene. Surveillance strategies to define appropriate antimicrobial therapies should include genotype-phenotype relationships for all major transmissible resistance genes and the characterization of mutations in relevant porins in organisms, like K. pneumoniae.
Keywords: Humans; Escherichia coli; Klebsiella pneumoniae; Escherichia coli Infections; Klebsiella Infections; beta-Lactams; beta-Lactamases; Bacterial Outer Membrane Proteins; Microbial Sensitivity Tests; beta-Lactam Resistance; Genotype; Phenotype; Mutation; Australia
Description: Accepted manuscript posted online 24 February 2016
Rights: Copyright © 2016, American Society for Microbiology. All Rights Reserved.
RMID: 0030048773
DOI: 10.1128/JCM.02153-15
Grant ID: http://purl.org/au-research/grants/nhmrc/1001021
http://purl.org/au-research/grants/nhmrc/1002076
http://purl.org/au-research/grants/nhmrc/1046886
Appears in Collections:Molecular and Biomedical Science publications

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