Treatment of extended-spectrum β-lactamases infections: what is the current role of new β-lactams/β-lactamase inhibitors?

Abstract

The widespread diffusion of extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales currently represents a major threat for public health worldwide. Carbapenems are currently considered the first-line choice for serious ESBL infections. However, the dramatic global increase in ESBL prevalence has led to a significant overuse of carbapenems that has promoted the selection and spread of carbapenemases, which might further prejudicated our ability to treat infections due to multidrug-resistant pathogens. Therefore, strategies to limit the use of carbapenems should be implemented. Although piperacillin-tazobactam should no longer be considered an alternative to carbapenems for definitive treatment of bloodstream infections due to ESBL-producing strains, it might still represent an alternative for step-down therapy or for low-to-moderate severity infection originating from urinary or biliary sources and when piperacillin-tazobactam minimum inhibitory concentration of 4 mg/l or less. Ceftazidime-avibactam and ceftolozane-tazobactam are both carbapenem sparing agents that appear interesting alternatives for treatment of serious ESBL infections. New β-lactams/β-lactamase inhibitors (BL/BLI), including cefepime-enmetazobactam, ceftaroline fosamil-avibactam, aztreonam-avibactam and cefepime-zidebactam, are also promising agents for treatment of ESBL infections, but further clinical data are needed to establish their efficacy relative to carbapenems. The role of carbapenems/β-lactamase inhibitors remain to be clarified. New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections.