Author:
Chrystal E J,Koch R L,McLafferty M A,Goldman P
Abstract
It has been suggested that the microbicidal effect of metronidazole is mediated by an intermediate in nitro group reduction. We have found that the addition of Escherichia coli enhances the lethal effect of metronidazole on Bacillus fragilis and suggest that this intermediate may form in one bacteria and kill another. Because acetamide forms during the reduction of metronidazole, we examined the possibility that the same partially reduced intermediate in metronidazole reduction may be both an intermediate in the formation of acetamide and the ultimate reactive form of metronidazole which is responsible for its bactericidal action. Thus, we determined the relationship between bacterial survival and the formation of acetamide when cultures of B. fragilis, Clostridium perfringens, and E. coli were incubated anaerobically in the presence of metronidazole. We found that the log of the early bacterial survival was proportional to the formation of acetamide. The rate of loss of metronidazole was not dependent on the concentration of bacteria in the medium, suggesting that any proposed intermediate formed at a rate which was proportional only to the concentration of metronidazole.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference17 articles.
1. Mammalian cell toxicity of nitro compounds: dependence upon reduction potential;Adams G. E.;Biochem. Biophys. Res. Commun.,1976
2. Electron-affinic sensitization. VII. A correlation between structures, one-electron reduction potentials, and efficiencies of nitroimidazoles as hypoxic cell radiosensitizers;Adams G. E.;Radiat. Res.,1976
3. Metronidazole (Flagyl), misonidazole (Ro 07-0582), iron, zinc and sulphur compounds in cancer therapy;Bahnemann D.;Br. J. Cancer,1978
4. Screening for the mutagenicity of nitro-group containing hypoxic cell radiosensitizers using Salmonella typhimurium strains TA 100 and TA 98;Chin J. B.;Mutat. Res.,1978
5. The selective toxicity of antimicrobial nitroheterocyclic drugs;Edwards D. I.;J. Gen. Microbiol.,1975
Cited by
62 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献