Epidemiology and Genetic Traits of Carbapenemase-Producing Enterobacterales: A Global Threat to Human Health.

Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided into three classes (A, B, and D) according to the Ambler classification system. Among these, KPC (class A), NDM, VIM, IMP (class B), and OXA-48-like (class D) represent the most important carbapenemases in terms of diffusion and clinical impact. CPE diffusion has been observed worldwide, with current endemicity in multiple territories around the world. In this context, the clonal spread and plasmid-mediated transmission of carbapenemases have contributed to the global spread of CPE worldwide and to the diffusion of carbapenemases among different Enterobacterales species. In recent years, novel molecules showing excellent in vitro and in vivo activity have been developed against CPE. However, the recent emergence of novel traits of resistance to these molecules has already been reported in several cases, mitigating the initial promising results. This review aims to provide an updated description of the major classes of carbapenemases, their global distribution, and future perspectives to limit the diffusion of CPEs.