title: [Development of beta-lactamase inhibitors].
abstract: The proportion of beta-lactamase producing bacteria in each species of clinical isolates is high (over 90%) in these years. According to the survey of bacterial resistance in 1995, higher proportion of resistant bacterial species against ampicillin, piperacillin (PIPC), cefazolin, cefotiam was observed. To overcome the bacterial resistance against these beta-lactam antibiotics, we have made a development of beta-lactamase inhibitor and its combination antibiotic. New beta-lactamase inhibitor, tazobactam (TAZ) showed strong inhibitory activity against various kinds of beta-lactamases including cephalosporinases. The combination antibiotic, TAZ/PIPC(TAZ combined with PIPC by 1 to 4) showed stronger antibacterial activity than PIPC against beta-lactamase producing stains. And also the activity of TAZ/PIPC was superior to PIPC in the mixed bacterial infection model in mouse. The in vitro and in vivo frequency of emergence of resistant bacteria from Enterobacteriacae treated with TAZ/PIPC was lower than that of PIPC or ceftazidime (CAZ). By these data, combined antibiotics with beta-lactamase inhibitor was effective to resolve the problems of bacterial resistances caused by beta-lactamases.
authors.affiliation: Antimicrobial Research Lab. Taiho Pharmaceutical Co., Ltd.
authors.forename: A
authors.initials: A
authors.lastname: Hyodo
authors.forename: F
authors.initials: F
authors.lastname: Higashitani
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: C
authors.initials: C
authors.lastname: Kunugita
authors.forename: N
authors.initials: N
authors.lastname: Unemi
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010878:Piperacillin / Q000494:pharmacology / Q000627:therapeutic use; D000078142:Tazobactam; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000145:classification
chemical_list: D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam; D010878:Piperacillin