Abstract
The kinetics of the lethal action of metronidazole and the formation of acetamide have been studied in a strain of Bacteroides fragilis which is relatively resistant to metronidazole. As with a susceptible strain of B. fragilis, the data are consistent with a model in which a labile intermediate in metronidazole metabolism interacts either with water to form acetamide or with a bacterium to cause its death. Although the relatively resistant strain grows more slowly than the susceptible one and is killed less rapidly by metronidazole, the resistant strain displays the same relationship between the lethal action of metronidazole and metronidazole metabolism to acetamide. The relatively resistant strain, like the susceptible one, has an enhanced lethal response to metronidazole in the presence of a strain of Escherichia coli. The results suggest that the proposed labile reactive intermediate of metronidazole forms more slowly in the resistant strains.
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Selected References
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- Chrystal E. J., Koch R. L., McLafferty M. A., Goldman P. Relationship between metronidazole metabolism and bactericidal activity. Antimicrob Agents Chemother. 1980 Oct;18(4):566–573. doi: 10.1128/aac.18.4.566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ingham H. R., Eaton S., Venables C. W., Adams P. C. Bacteroides fragilis resistant to metronidazole after long-term therapy. Lancet. 1978 Jan 28;1(8057):214–214. doi: 10.1016/s0140-6736(78)90655-4. [DOI] [PubMed] [Google Scholar]
- Koch R. L., Chrystal E. J., Beaulieu B. B., Jr, Goldman P. Acetamide--a metabolite of metronidazole formed by the intestinal flora. Biochem Pharmacol. 1979 Dec 15;28(24):3611–3615. doi: 10.1016/0006-2952(79)90407-6. [DOI] [PubMed] [Google Scholar]
- Koch R. L., Goldman P. The anaerobic metabolism of metronidazole forms N-(2-hydroxyethyl)-oxamic acid. J Pharmacol Exp Ther. 1979 Mar;208(3):406–410. [PubMed] [Google Scholar]
- Prince H. N., Grunberg E., Titsworth E., DeLorenzo W. F. Effects of l-(2-nitro-l-imidazolyl)-3-methoxy-2-propanol and 2-methyl-5-nitroimidazole-l-ethanol against anaerobic and aerobic bacteria and protozoa. Appl Microbiol. 1969 Nov;18(5):728–730. doi: 10.1128/am.18.5.728-730.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]