Contribution of acrB upregulation & OmpC/Ompk36 loss over the presence of bla(NDM) towards carbapenem resistance development among pathogenic Escherichia coli & Klebsiella spp.

BACKGROUND & OBJECTIVES: The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is an emerging clinical problem. Hence, in this study, the plausible role of extended-spectrum beta-lactamases (ESBLs)/carbapenemases, OmpC/Ompk36, acrB and their combinations was explored among CRE. METHODS: The minimum inhibitory concentration (MIC) of meropenem, enzyme-phenotypes (ESBLs/IR and metallo-beta-lactamase (MBL)/non-MBL carbapenemase), genotypes (bla(TEM,) bla(SHV) and bla(CTX-M); bla(NDM) and bla(VIM;) bla(KPC) and bla(OXA-48)-like variants), acrB and outer membrane protein (OMP) expressions were analyzed with a total of 101 non-duplicate clinical isolates, obtained from various samples of patients visiting two tertiary care units of Eastern India during May 2013 - October 2016. This included Escherichia coli (n=36) and Klebsiella pneumoniae (n=65), categorized into two groups, namely Group I (resistant to all carbapenems; n=93; E. coli=34 and Klebsiella spp.=59) and Group II (non-resistant to all the carbapenems; n=8; E. coli=2 and Klebsiella spp.=6). RESULTS: Though 88.17 per cent of Group I isolates exhibited ESBL property, the presence of carbapenemase activity (70.96%) and that of bla(NDM) gene (42/66: 63.63%) indicated their contributions towards the emergence of CRE. Further, porin loss and/or efflux pump activation among ESBL/carbapenemase-producing isolates heightened the MIC of meropenem from 64 to 256 mg/l (range exhibited by only ESBL/carbapenemase-producing isolates) to >256 mg/l. INTERPRETATION & CONCLUSIONS: These findings implied the major contribution of porin loss and/or efflux pump activation over the presence of ESBLs/carbapenemases in imparting carbapenem resistance in pathogenic bacteria.