New Delhi Metallo-β-Lactamase (NDM-1): An Updates

Abstract

New Delhi metallo-β-lactamase (NDM-1) is a novel broad spectrum carbapenemase with ability to inactivate all β-lactams except aztreonam. However, most of the NDM-1-producers also produce aztreonam hydrolysing-β-lactamases thereby making these pathogens absolutely resistant to all β-lactams. The bla(NDM-1) gene encodes a 27.5 kDa protein of 269 amino acids. It shares very little identity with other metallo-β-lactamases. Maximum identity has been observed to VIM-1/VIM-2 (32.4%). This mini-review is an update of the scientific literature for the said enzyme. Following the recommendation of David livermore, we further propose to combine "aztreonam" and "inhibitor of the most frequently encountered aztreonam hydrolysing-β-lactamases in a given setting" as a possible strategy against NDM-1-producers. The inhibitor should be 'versatile' as well, i.e. it should have the ability to inhibit most of the variants of aztreonam hydrolysing-β-lactamases prevalent in the concerned setting. We strongly recommend surveillance studies using aztreonam/NXL-104-combination against NDM-1-producing pathogens in different geographical regions across the globe.

In VivoEfficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae

“…The rate at which the metallo-␤-lactamase NDM-1 has disseminated globally among members of the family Enterobacteriaceae is alarming (2). Without antimicrobials with novel mechanisms of action readily available, evaluation of the potential clinical utility of existing agents for the treatment of infections caused by these resistant pathogens is imperative.…”

“…Since then, it has disseminated at a high rate among Enterobacteriaceae isolates both within the Indian subcontinent and worldwide (2)(3)(4). The treatment options for infections caused by NDM-1-producing isolates are extremely limited, as these enzymes are known to hydrolyze penicillins, cephalosporins, and carbapenems while typically retaining susceptibility to only colistin and tigecycline (2), neither of which has been shown to be a dependable option on the basis of in vitro time-kill data and case reports (5)(6)(7)(8). Aztreonam is not readily inactivated by metallo-␤-lactamases, including NDM-1, and may represent another potential option for therapy (1,9).…”

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

“…However, there are two major limitations for their use. First, there are no published clinical data, and second, many of the Enterobacteriaceae isolates that produce MBLs or oxacillinases additionally carry ESBLs or other resistant determinants that confer resistance to aztreonam and extendedexpectrum cephalosporins [Falagas et al 2011;Shakil et al 2011]. For isolates coexpressing ESBLs and MBLs, a combination of aztreonam with a b-lactamase inhibitor has been proposed [Shakil et al 2011;Livermore et al 2011a].…”

Escherichia Coli productora de Nueva Delhi metalo-β-lactamasa en Colombia: reporte de caso

“…La Nueva Delhi metalo-β-lactamasa (NDM) es una carbapenemasa adquirida de clase B, inicialmente reportada en un paciente suizo en un hospital de Nueva Delhi, India, que confiere resistencia a todos los b-lactámicos 1,3 . Aunque algunos reportes indican que la NDM no hidroliza monobactámicos, la mayoría de cepas productoras de NDM también expresan enzimas que podrían hidrolizar monobactámicos, haciendo a estas muy difíciles de controlar 3,4 . La E. coli productora de carbapenemasa tipo NDM fue descrita inicialmente en 2009 en Suecia en pacientes pro-venientes de India, y desde entonces se han reportado múltiples casos alrededor del mundo 5 .…”