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-upon-Tyne SYNOPSIS Metronidazole was found to be active against Bacteroides fragilis strains isolated from human lesions. The minimal inhibitory concentrations (MIC) were from 0-16 to 2-5 ,ug/ml and the minimal bactericidal concentrations (MBC) were from 0-16 to 2 5 ,ug/ml; usually the MIC and MBC figures were equivalent. These levels are easily attainable in the serum following normal therapeutic doses. The drug is not toxic and side effects are rare and it would therefore seem highly suitable for treating Bacteroides infections and also may be considered prophylactically in certain situations that are described.Organisms of Bacteroides species and particularly Bact. fragilis have been incriminated in a large number of infections. They are frequently observed in sepsis following gastrointestinal surgery (Gillespie and Guy, 1956), in puerperal sepsis (Rotheram and Schick, 1969), lung abscess (Tillotson and Lerner, 1968), and brain abscess (Ingham, Selkon, Codd, and Hale, 1970). Lincomycin has been shown to possess bactericidal activity in vitro against Bacteroides species (Ingham, Selkon, Codd, and Hale, 1968;Nastro and Finegold, 1972) metronidazole was determined using two-fold serial dilution in 10% blood agar incorporating the drug in the medium at a starting concentration of 50 ,ug/ml with the first isolates and at 10 p,g/ml in the later estimations. A 48-hour culture grown on 10% blood agar under anaerobic conditions at 37°C was used to inoculate the drug-containing blood agar plates. The latter were incubated overnight at 37°C in an anaerobic jar under 90 % hydrogen and 10 % carbon dioxide. The MIC values were recorded after 24 hours' incubation and the minimum bactericidal concentrations (MBC) were determined by the replica plate method of Elek and Hilson (1954) using 10% blood agar plates. The recovery plates were incubated overnight under anaerobic conditions. The criterion for bactericidal effect was that there should be no colonies on the corresponding replica plates. PATHOGENICITY EXPERIMENTSAttempts to produce lesions in animals were made. Two slopes of horse blood agar were inoculated with each strain, incubated for 48 hours, and the organisms on each slope washed off with 1I0 ml of saline. This suspension was injected in 0-03 ml amounts intracerebrally into 20 g albino mice. The remainder of the saline suspension was diluted with 5% hog mucin and iWected intraperitoneally in 0-5 ml volumes into 20 g mice. Similar slopes were inoculated and harvested and 0 5 ml volumes of the suspension injected subcutaneously into 150 g guinea pigs and into 1-5 kg rabbits.

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SUMMARY Metronidazole, a compound widely used in man with minimal side effects, has been shown to be highly active against experimental infections of Clostridium tetani and Cl. welchii in mice. It is too early to forecast what role the compound might have in the chemoprophylaxis of these infections in man.

Squires and McFadzean (1962) reviewed the question of strain sensitivity of Trichomonas vaginalis to metronidazole. Since then examinations of the sensitivities of strains isolated from occasional patients who had apparently not responded to treatment with metronidazole have been continued. The results of these examinations are described.It was also thought worth while to examine the strain sensitivities of random cultures of the parasite lest there had been a change which was not as yet reflected by therapeutic failures. At the same time, in view of the observation by Nicol, Evans, McFadzean, and Squires (1966) that organisms of the genus Mimae could "inactivate" the drug, the vaginal flora of these patients were also examined for the presence of organisms capable of inactivating the compound. MethodsThe techniques for isolation and sensitivity testing of the parasites in the case of patients who had apparently failed to respond to treatment were as described by Squires and McFadzean (1962). In the case of the random samples, which came from the London Hospital, the Middlesex Hospital, and St. Thomas' Hospital, the initial media used for isolating the organisms did not contain antibiotics. Subsequent subcultures were made into medium containing antibiotics before determining the sensitivities of the trichomonads to metronidazole. The initial cultures were also plated out on blood agar. The bacteria were subsequently inoculated into tryptose phosphate medium containing 10 and/or 100 ,ug./ml. metronidazole. After incubation for 24 hours at 37°C. the tubes were centrifuged at 4,000 r.p.m. for 10 minutes, the supernatant was removed and was sterilized by being held at 100°C. for 20 minutes, and the metronidazole content of the supernatant was estimated polarographically. These procedures were undertaken initially with the mixed flora present. If inactivation occurred, the bacterial species were then separated, identified where possible, and tested individually for their abilities to inactivate the compound. *Received for publication October 8, 1968. Results 45 cultures were submitted from different parts of Great Britain over the period 1962 to 1968, from patients who had apparently not responded to treatment with metronidazole. Trichomonads were isolated and cultured from 25 (56 per cent.) of these and all were found to be sensitive to 0 5 to 1 ,ug./ml. metronidazole. Trichomonads were not grown from twenty samples, and in eleven of these there was no evidence of trichomonads having been inoculated as shown by the absence of dead organisms in centrifuged deposits of the cultures.22 of the specimens were also examined for the presence of organisms capable of inactivating metronidazole. Of these, eleven (50 per cent.) had organisms present which inactivated the drug, as assessed polarographically. In these instances the organisms were not identified. In some cases, however, where no organisms capable of inactivation were found, it was shown that the absorption of metronidazole, as judged by serum concentrations, ...