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

Purpose of review 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. Recent findings 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 4mg/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. Summary 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.