Semi-mechanistic modeling of resistance development to β-lactam and β-lactamase-inhibitor combinations.

The use of β-lactam (BL) and β-lactamase inhibitor (BLI) combinations, such as piperacillin-tazobactam (PIP-TAZ) is an effective strategy to combat infections by extended-spectrum β-lactamase-producing bacteria. However, in Gram-negative bacteria, resistance (both mutational and adaptive) to BL-BLI combination can still develop through multiple mechanisms. These mechanisms may include increased β-lactamase activity, reduced drug influx, and increased drug efflux.