Impact of the New Delhi metallo-beta-lactamase on beta-lactam antibiotics

Abstract

Since the first New Delhi metallo-beta-lactamase (NDM) report in 2009, NDM has spread globally causing various types of infections. NDM-positive organisms produce in vitro resistance phenotypes to carbapenems and many other antimicrobials. It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes. There are many instances where good clinical outcomes are described, despite a mismatch between administered antimicrobials and resistant in vitro susceptibilities. Available in vitro data for either monotherapy or combination therapy does not provide an explanation for these observations. However, animal studies do begin to shed more light on this phenomenon. They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype. As such, previously abandoned therapies, particularly carbapenems and beta-lactamase inhibitor combinations, may retain utility against infections caused by NDM producers.

Keywords:

• carbapenemase
• metallo-beta-lactamase
• resistance

Disclosure

MD Nailor has been involved in consulting/grants and speaker bureaus for Astellas and Merck pharmaceutical companies. DP Nicolau has been involved in consulting/grants and speaker bureaus for AstraZeneca, Cubist, Merck, Tetraphase, and Actavis pharmaceutical companies. The other authors report no conflicts of interest in this work.