New β-Lactamase Inhibitors in the Clinic

Given the serious medical burden of beta-lactamases, many approaches are being used to identify candidate agents for beta-lactamase inhibition. Here, we review two beta-lactam-beta-lactamase inhibitor (BL-BLI) combinations, ceftolozane-tazobactam and ceftazidime-avibactam that recently entered the clinic. In addition, we focus on BL-BLI combinations in preclinical development that have demonstrated activity in clinical isolates via susceptibility testing and/or in in vivo models of infection. We highlight only the BLIs that are able to reduce the Clinical Laboratory Standards Institute (CLSI) breakpoints for the BL partner into the susceptible range. Our analysis includes the primary literature, meeting abstracts, as well as the patent literature.