Efficacy of Piperacillin Combined with the Penem β-Lactamase Inhibitor BLI-489 in Murine Models of Systemic Infection

The in vivo efficacy of piperacillin in combination with the penem inhibitor BLI-489 was determined using acute lethal systemic infections in mice. On the basis of preliminary results with various ratios, a dosing ratio of 8: 1 was found to be optimal for retention of enhanced efficacy. Piperacillin- BLI-489 dosed at an 8: 1 ratio was efficacious against murine infections caused by class A (including extended-spectrum beta-lactamases), class C (AmpC), and class D beta-lactamase-expressing pathogens.