BARRIER EFFECT OF NORMAL MICROBIOTA AGAINST CLOSTRIDIUM-DIFFICILE MAY BE INFLUENCED BY DRUGS DEVOID OF ANTIBIOTIC-ACTIVITY

Germ-free mice associated with human faecal microorganisms were used as a model of the microbial barrier against C. difficile. In this model, the production of toxins A and B by C. difficile was studied after oral treatment with phenothiazines (chlorpromazine and cyamemazine), methotrexate and an antibiotic (clindamycin). After 4 wks oral administration of chlorpromazine (10 mg/kg/day) and cyamemazine (35 mg/kg/day), neither the number of C. difficile nor the levels of toxin A and B in faecal pellets differed from those of untreated mice. C. difficile failed to establish in the intestine of mice colonised with human faecal microorganisms; neither toxin A nor B were detected in the faecal pellets of these animals. After treatment with clindamycin (10 d; 75 mg/kg/day) and methotrexate (4 wks; 250 mg/kg/day), the concentration of C. difficile in the faecal pellets was stable, and toxin B, but not toxin A, was detected. These results show that both clindamycin and methotrexate are able to disturb the intestinal barrier effect, whereas phenothiazines had little such effect.