Mobilization of Carbapenemase-Mediated Resistance in Enterobacteriaceae

Abstract:

There has been a dramatic increase in the last decade in the number of carbapenem-resistant Enterobacteriaceae, often leaving patients and their providers with few treatment options and resultant poor outcomes when an infection develops. The majority of the carbapenem resistance is mediated by bacterial acquisition of one of three carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], oxacillinase-48-like [OXA-48], and the New Delhi metallo-β-lactamase [NDM]). Each of these enzymes has a unique global epidemiology and microbiology. The genes which encode the most globally widespread carbapenemases are typically carried on mobile pieces of DNA which can be freely exchanged between bacterial strains and species via horizontal gene transfer. Unfortunately, most of the antimicrobial surveillance systems target specific strains or species and therefore are not well equipped for examining genes of drug resistance. Examination of not only the carbapenemase gene itself but also the genetic context which can predispose a gene to mobilize within a diversity of species and environments will likely be central to understanding the factors contributing to the global dissemination of carbapenem resistance. Using the three most prevalent carbapenemase genes as examples, this chapter highlights the potential impact the associated genetic mobile elements have on the epidemiology and microbiology for each carbapenemase. Understanding how a carbapenemase gene mobilizes through a bacterial population will be critical for detection methods and ultimately inform infection control practices. Understanding gene mobilization and tracking will require novel approaches to surveillance, which will be required to slow the spread of this emerging resistance.