Informing the development of β-lactam—β-lactamase inhibitor combinations through a comparison of in vitro data

Mortality rates associated with antimicrobial resistance are increasing at an alarming rate and are becoming one of the most serious threats to global health. Paradoxically, investment in the development of new antibacterial agents is limited as a result of multiple factors, including resistance, which have the potential to shorten the clinical lifespan of an antibacterial agent. Improvements in the tools used to predict the success or failure of drug candidates have been shown to reduce the overall cost of the drug discovery process. β-Lactamases are drug-modifying enzymes that can hydrolyse and inactivate the β-lactam antibiotics. The development of β-lactamase inhibitors (BLIs) can enable the re-sensitisation of bacteria previously resistant to the β-lactams (BLs). There are nine β-lactam/β-lactamase inhibitor (BL/BLI) combinations available for use in clinical practice. This review presents a summary of the in vitro performance of the nine currently marketed BL/BLI combinations in synergy assays, serving as a comparative reference for researchers developing new combinations.