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[Development of beta-lactamase inhibitors]
A Hyodo1, F Higashitani, K Nishida
1Antimicrobial Research Lab. Taiho Pharmaceutical Co., Ltd.
Summary
Beta-lactamase producing bacteria are highly resistant to antibiotics. A new combination of piperacillin (PIPC) with tazobactam (TAZ) effectively combats this resistance, showing superior activity against resistant bacterial strains.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- High prevalence of beta-lactamase producing bacteria exceeds 90% in clinical isolates.
- Significant bacterial resistance observed against ampicillin, piperacillin (PIPC), cefazolin, and cefotiam since 1995.
Purpose of the Study:
- To develop a beta-lactamase inhibitor and combination antibiotic to overcome existing bacterial resistance.
- To evaluate the efficacy of tazobactam (TAZ) as a beta-lactamase inhibitor and its combination with piperacillin (TAZ/PIPC).
Main Methods:
- Development of a novel beta-lactamase inhibitor, tazobactam (TAZ).
- Assessment of TAZ's inhibitory activity against various beta-lactamases, including cephalosporinases.
- Evaluation of the antibacterial activity of TAZ/PIPC (1:4 ratio) in vitro and in vivo, including mixed bacterial infection models in mice.
Main Results:
- Tazobactam (TAZ) demonstrated strong inhibitory activity against diverse beta-lactamases.
- The TAZ/PIPC combination exhibited enhanced antibacterial activity compared to PIPC alone against beta-lactamase producing strains.
- TAZ/PIPC showed superior efficacy in a mouse mixed bacterial infection model and a lower frequency of resistant bacterial emergence than PIPC or ceftazidime (CAZ).
Conclusions:
- Combined antibiotics with beta-lactamase inhibitors are effective in addressing bacterial resistance.
- The TAZ/PIPC combination offers a promising strategy to combat beta-lactamase-mediated bacterial resistance.