title: Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae.
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.
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Agyekum
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia alicia.fajardolubian@sydney.edu.au jonathan.iredell@sydney.edu.au.
authors.forename: Alicia
authors.initials: A
authors.lastname: Fajardo-Lubián
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Ai
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Ginn
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zong
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Guo
authors.affiliation: Women's and Children's Hospital, Adelaide, South Australia, Australia Departments of Pathology, Paediatrics, and Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Turnidge
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Sally R
authors.initials: SR
authors.lastname: Partridge
authors.affiliation: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia alicia.fajardolubian@sydney.edu.au jonathan.iredell@sydney.edu.au.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Iredell
mesh_terms: D001315:Australia; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D004927:Escherichia coli Infections / Q000382:microbiology; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D047090:beta-Lactams; D001618:beta-Lactamases