Effects of tazobactam on the frequency of the emergence of resistant strains from Enterobacter cloacae, Citrobacter freundii, and Proteus vulgaris (beta-lactamase derepressed mutants).
When Enterobacter cloacae, Citrobacter freundii, and Proteus vulgaris were treated with piperacillin (PIPC) in combination with tazobactam (TAZ), the in vitro frequency of emergence of resistant strains (beta-lactamase producing mutants) was lower than with PIPC or ceftazidime (CAZ) treated bacteria. In a mouse intraperitoneal infection model caused by E. cloacae, beta-lactamase derepressed mutants were detected following therapy with PIPC or CAZ, although no derepressed mutants were detected after treatment with PIPC in combination with TAZ. This suppression of the selection of derepressed mutants, which produce large amounts of beta-lactamases, by the combination of TAZ and PIPC suggests that the combination delays the increase of resistant mutants compared with PIPC alone.
Higashitani
F
F
Anticancer and Antimicrobial Research Laboratory, TAIHO pharmaceutical Co., Ltd., Tokushima, Japan.
Nishida
K
K
Hyodo
A
A
Inoue
M
M
D000818:Animals; D016971:Citrobacter freundii / Q000187:drug effects* / Q000201:enzymology; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D016972:Enterobacter cloacae / Q000187:drug effects* / Q000201:enzymology; D004756:Enterobacteriaceae Infections / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D011514:Proteus vulgaris / Q000187:drug effects* / Q000201:enzymology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam; D010878:Piperacillin