SUMMARY We have studied the antimicrobial action of metronidazole against Bacteroides fragilis and Escherichia coli both in pure cultures and in combination. Concentrations of metronidazole above the minimal inhibitory concentration (MIC) produced a marked bactericidal effect on B fragilis at six hours. E coli however showed only a slight and transitory decrease in population when exposed to concentrations of metronidazole close to its MIC. Kinetic studies of this drug's effect on mixed cultures of both organisms showed mutual bactericidal synergy between E coli and metronidazole against B fragilis and between B fragilis and metronidazole against E coli.These in vitro findings agree with the results obtained in vivo by other authors.It has been shown that metronidazole reduces mortality from experimental peritonitis induced in rats by inoculation of caecal content or mixtures of facultative and anaerobic bacteria from the gut.' It has been suggested that metronidazole may possess an antimicrobial effect not only against anaerobic bacteria, especially Bacteroides fragilis, but also against aerobic and facultative organisms, although the results published are to a certain extent contradictory.'5 While it has been shown that certain strains of Escherichia coli are, in specific experimental conditions, susceptible to metronidazole,3 there is much doubt as to interaction between this drug and the mixed flora of the gut.The antimicrobial action of metronidazole against anaerobes and possibly aerobic and facultative bacteria also is an important feature of this drug and one that is not shared by others chemically unrelated to it but highly active against certain anaerobes like clindamycin.'Most of the literature on metronidazole, E coli and B fragilis interaction has been mainly concerned with the drug's effect on E coli. This paper studies the kinetic effect of metronidazole on both E coli and B fragilis as well as the interaction of these three variables in an in vitro system. Material and methods
BACTERIAL STRAINSOne freshly isolated strain of B fragilis and another of E coli were studied. Their anaerobic minimal inhibitory concentration (MIC) were 1 and 64 ,ug/ml of metronidazole, respectively.
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