Current Promising Antibiotics and Future Approaches in Combating Carbapenemase-Producing Enterobacteriaceae

Abstract

Carbapenem-resistant (CR) Gram-negative bacilli, including Enterobacteriaceae and the non-fermenters, represent the most notorious pathogens due to the high incidence of morbidity and mortality, especially in immunocompromised patients in intensive care units. Carbapenem resistance is mainly associated with the production of carbapenemases, which are β-lactamases belonging to different Ambler classes (A, B, D) that can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, hydrolyzing a wide variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are both clinical, posing significant challenges in the treatment of healthcare-associated infections by compromising the activity of the last-resort antibiotics, and epidemiological, due to their dissemination across almost all geographic regions. An important advancement is a handful of newly launched antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-resistant Enterobacteriaceae (CRE). The most appropriate antimicrobial therapy to treat CRE infections is still controversial. Combination therapy is preferred over monotherapy due to its broad-spectrum coverage, synergic activity, and low probability of selecting resistance. In this mini-review, current and future promising antibiotics that are currently under investigation for winning the war against the emerging CRE are discussed.