Efficacy of piperacillin combined with the Penem beta-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.
Petersen
Peter J
PJ
Infectious Disease Research, Wyeth Research, Pearl River, NY 10965, USA. petersp@wyeth.com
Jones
C Hal
CH
Venkatesan
Aranapakam M
AM
Bradford
Patricia A
PA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000188:drug therapy*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007769:Lactams / Q000008:administration & dosage*; D051379:Mice; D010878:Piperacillin / Q000008:administration & dosage*; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; C539934:BLI-489; D007769:Lactams; D065093:beta-Lactamase Inhibitors; D010878:Piperacillin