Response of a 'susceptible' Escherichia coli to metronidazole therapy: an investigation using experimental subcutaneous abscesses.

Earlier experiments under anaerobic conditions in vitro had indicated that Gram-negative facultative anaerobes were susceptible to therapeutically attainable concentrations of metronidazole. This prompted us to study the response of one such strain to metronidazole therapy. Mice with 3-day-old subcutaneous abscesses induced by 'susceptible' Escherichia coli (accompanied by potentiating agent and obligately anaerobic Bacteroides fragilis) were given metronidazole by mouth (250 mg/kg/dose 12 hourly) either as a two- or a four-dose course. This therapy reduced the viable numbers of E. coli/abscess by a mere 0.3 log10 and 0.7 log10, respectively. Assays showed that concentrations of metronidazole in abscess-contents compared favourably with those in the earlier in vitro experiments. But measurement of redox potentials in abscesses indicated that the conditions in these (-191 mV vs. Ag/AgCl) were not nearly as reduced as those in experiments in vitro (-650 mV). This, and the known dependence of metronidazole on low redox potentials for expression of its antimicrobial ability, appears to be the explanation for the poor anticoliform effect in the subcutaneous abscess model. Full assessment of the clinical implications of these observations must await the availability of data regarding redox potentials in clinical situations.