Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae
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 inEnterobacteriaceaein Sydney, Australia.Escherichia coli(n= 200) andKlebsiella 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 inK. pneumoniae, with a loss or change in the outer membrane porin protein OmpK36. We demonstrated mutations inompK36or absence of OmpK36 in all isolates in which reduced susceptibility to ertapenem (MIC, >1 mg/liter) was evident. Ertapenem nonsusceptibility inK. pneumoniaewas 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, likeK. pneumoniae.