Comparative activity of metronidazole and tinidazole against Clostridium difficile and Peptostreptococcus anaerobius

Abstract

Broth dilution MICs of metronidazole against 38 strains of Clostridium difficile (0.13 ,ug/ml) and 11 strains of Peptostreptococcus anaerobius (0.11 ,Lg/ml) were lower than those of tinidazole (0.16 and 0.17 ,ug/ml, respectively). As molar concentrations the nitroimidazoles were equally active. The MICs of the two drugs correlated positively, and the relative activity of tinidazole increased with decreasing susceptibility of both species.Metronidazole is active against anaerobic bacteria, and it has been found to be clinically useful in a variety of anaerobic infections. The study of other 5-nitroimidazole drugs may add to therapeutic alternatives and to the understanding of their mechanisms of action. The family comprises numerous drugs, and over 10-fold differences in in vitro activity against Bacteroides fragilis have been reported, even if only the compounds used in human medicine are considered (19,25). Comparative studies have been largely confined to the model pathogen B. fragilis, which has been found to be more susceptible to tinidazole than to metronidazole (7,14,16,19,25,26). The same relationship between the two drugs has been found with Giardia lamblia in vitro (18) and in the treatment of giardiasis (17). These findings show that the differences between closely related 5-nitroimidazoles may be clinically significant and suggest that relative activities against other target organisms might be predictable by generalizations from studies of B. fragilis as a model.A few studies of metronidazole and tinidazole against clostridia and peptostreptococci have revealed that the latter drug may be relatively less active (Table 1), which is evidence against the generalization given above. The reports also show that the interlaboratory variation of the' MIC of either drug greatly exceeds the usual difference between the MICs of the two drugs. Thus, only parallel experiments with metronidazole and tinidazole allow their comparison. To confirm and extend this comparison, we performed such experiments with Clostridium difficile and Peptostreptococcus anaerobius. MATERIALS AND METHODSBacteria. A total of 38 strains of C. difficile were isolated from fecal samples submitted for the diagnosis of antibioticassociated colitis, and 11 strains of P. anaerobius were obtained from various clinical pus samples. Their identification was based mainly on colony and Gram stain morphology, the API 20A strip (API System S.A., MontalieuVercieu, France), and the metabolic end product profile in peptone-yeast-glucose broth (12). The gas-chromatographic method has been described previously in detail (15). P. anaerobius was handled inside an anaerobic cabinet (model 800, anaerobic environmental system; Capco, Sunnyvale, * Corresponding author.Calif.) and incubated in transfer modules (model 830; Capco). To avoid contamination by spores, clostridia were not allowed in the cabinet and C. difficile was incubated in separate premises in the GasPak system (BBL Microbiology Systems, Cockeysville, Md.), which involved exposure to air for a ...

Reassessment of Clostridium difficile Susceptibility to Metronidazole and Vancomycin

“…difficile is considered susceptible to metronidazole in most institutions, and tests to assess the in vitro activity of metronidazole against C. difficile isolates are rarely performed in most (20,23,34,36,50). It is well known, however, that CDAD may develop in patients during metronidazole therapy (43) and that isolates of C. difficile resistant to metronidazole in vitro had already been reported anecdotally in 1981 (37), although these facts are not necessarily related.…”

Penetration of tinidazole into skin blister fluid following its oral administration

“…blister fluid was obtained by the cantharidin blister technique, as previously described [8][9][10]. Each blister was punctured once with a sterile syringe, using different blisters 4,6,8,12,18 and 24 h after dosing. The patches of polyethylene sheeting, approximately 2 cm in diameter, on which the 0.25 % cantharidin ointment had been placed, were applied 16 h before ingestion of the drug for blisters punctured 4~--18 h after dosing; the last patch was applied 4 h after drug administration.…”

“…In the 1970s it was discovered that nitroimidazoles, including tinidazole, were also effective against anaerobic bacteria [2]; for instance, tinidazole is one of the most active bactericidal agents for treating Bacteroidesfragilis [3,4].…”

Clostridium-difficile-assoziierte Diarrhö – ein Update

“…Ob Breitspektrumfluorochinolone mit verbesserter Aktivität gegen Anaerobier (derzeit nur Moxifloxacin im Handel) ein höheres Risiko haben als beispielsweise Levofloxacin, ist nicht abschließend geklärt [37,38]. Im Rahmen von Ausbruchsuntersuchungen konnten klonale Toxin-A-negative, Toxin-B-positive C.-difficile-Stämme isoliert werden, die hochgradig resistent gegen Fluorochinolone waren [36,39] [52,53]. Teicoplanin kann eine Alternative zu Vancomycin sein [54].…”