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232 Hermsen and RotschaferWhile metronidazole exhibits activity against multiple obligate anaerobes, thedrug is not considered to be active against aerobic bacteria. Conversely, someresearchers argue that metronidazole exhibits activity against Escherichia coli whenpresent in a mixed infection with B. fragilis (8,9). Interestingly, Chrystal et al. foundincreased effectiveness of metronidazole against B. fragilis in the presence of E. coli(10). The authors hypothesize that this effect may have been due to the ability ofcytotoxic intermediates to be formed in the E. coli and to diffuse into the mediumto kill the Bacteroides spp. These differences in activity could not be confirmed in amore recent mixed infection study (11). However, the relationships between thevarious microorganisms and the different antibiotics involved in polymicrobialinfections are difficult to separate.PharmacokineticsMetronidazole is almost completely absorbed, with a bioavailability of over 90%,when given via the oral route (12). Metronidazole is a fairly small molecular entitywith a molecular weight of 171.16 (13). The protein binding of metronidazole is low(