Escherichia coli encoding blaNDM-5 associated with community-acquired urinary tract infections with unusual MIC creep-like phenomenon against imipenem.

Abstract

Carbapenemase-producing Escherichia coli are a major clinical concern. The current study aimed to identify NDM-5-producing E. coli associated with community-acquired urinary tract infections (UTIs) co-harbouring extended-spectrum β-lactamases (ESBLs) and showing a phenomenon of imipenem minimum inhibitory concentration (MIC) creep. A total of 973 urine samples were collected from females aged between 18-49 years diagnosed with UTI in Northeast India (June 2014-July 2016). Isolates were identified by standard microbiological methods. The presence of blaNDM and ESBL genes was determined by PCR and sequencing. PCR-based replicon typing was performed. Plasmid stability of all β-lactamase-producers and their transformants was analysed by serial passage, and the MIC creep phenomenon was analysed by studying revertants. Among 34 blaNDM-5-positive E. coli isolates, 21 (61.8%) co harboured blaCTX-M-15, followed by multiple combinations of genes. This study revealed diverse plasmid types (HI1, I1, FIA+FIB, FIA and Y). The strains showed progressive plasmid loss after 31 passages. Most if the isolates had MICs of 0.5μg/mL and 1μg/mL to imipenem, ertapenem and meropenem. However, on studying the MIC creep phenomenon, the MIC was found to be elevated from 0.5μg/mL to 64μg/mL and from 1μg/mL to 128μg/mL. Analysis of revertants shows that the MIC of most NDM-positive isolates was reduced to 16μg/mL after the 30th serial passage. This study observed a unique phenotype of NDM-producers that has not been reported previously. The observed phenomenon poses a global threat as these pathogens may evade phenotypic screening by routine laboratories.