The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens.

Keywords: Enterobacteriaceae infections; adult; antibacterial agents; carbapenemases; carbapenems; child; drug resistance; epidemiology; global health; gram-negative bacteria.

Figure 1.

Global distribution of carbapenemases in Enterobacteriaceae, by country and region. Data are adapted from [, , , , , –40]. ^aKPCs are endemic in some US states; ^bOXA mainly refers to OXA-48, except in India, where it refers to OXA-181. Abbreviations: IMP, active on imipenem metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillinase-type carbapenem-hydrolyzing β-lactamase; VIM, Verona integron-encoded metallo-β-lactamase.