S U M M A R YThe antimicrobial drug 1-methyl-2-nitro-~-vinylimidazole (MEV) preferentially bjocked DNA synthesis, was mutagenic and induced coliphage h in Escherichia coli. The antibacterial effects of MEV are the consequences of repairable damage to DNA, as shown by hypersensitivity of recA and uvr strains to MEV and related drugs, stimulation by MEV of DNA turnover which was dependent on the product of the uvrA gene, and the presence of cross-links in DNA from MEV-treated bacteria.

The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine. Drug concentrations used were similar to those attainable in human urine. The combination was more effective than the individual drugs and than a combination of Tmp plus sulfamethoxazole (Smx). Tmp was bactericidal in urine and blocked the emergence of Ramp-resistant bacteria. Ramp was responsible for most of the bactericidal action of the combination but also potentiated the bactericidal activity of Tmp. Ramp suppressed the selection of thy- (Tmp-resistant) (6,(13)(14)(15)(16). One should recognize, however, particularly when comparing the efficacies of different antibacterial combinations, that upon administration of therapeutic doses the concentrations reached at the site of infection are generally much higher than those for which synergy or additivity can be demonstrated.

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