Medicina Molecular e Genética

New Delhi Metallo Beta Lactamase: Menace and its Challenges

Abstract

Kashyap A, Rani Gupta, Sharma R, Verma VV, Gupta S and Pradeep Goya

Clinicians have been facing an enormous challenge of treating infections caused by multiple drug resistant (MDR) pathogens since long. The latest and most alarming of such challenge is the emergence of New Delhi Metallo-β-Lactamase-type 1 (NDM-1) producing clinical isolates. NDM-1 is a metallo β-lactamase that confers resistance to all β-lactam antibiotics including carbapenems generally regarded as last resort to treat infections. NDM-1 is part of a huge conjugative plasmid blaNDM capable of rapid dissemination via horizontal gene transfer, transposition and recombination. Therefore, it has become a matter of global concern now as these pathogens have surpassed all geographical barriers and are threatening the public health all over the world. In addition to this, NDM-1 gene coexists with other resistance determinants such as other MBLs or porin mutations. Plasmid also carries genes conferring resistance to other antibiotic classes such as 16S RMTases, qcr, or mcr-1 gene imparting resistance to aminoglycosides, fluroquinolones and colistin respectively making current therapeutic recourse ineffective. If not addressed immediately, this resistance and its dissemination will bring us to a therapeutic dead end. In the present review, we have discussed the global spread of NDM-1 and its variants, its structural challenges that currently limit inhibitor drug designing, along with focusing some light on immediate measures that can be adapted at healthcare facilities with review of recent pharmacologic agents under research effective against NDM-1.