SHEDDING OF CLOSTRIDIUM-DIFFICILE, FECAL BETA-LACTAMASE ACTIVITY, ANDGASTROINTESTINAL SYMPTOMS IN 51 VOLUNTEERS TREATED WITH ORAL CEFIXIME

Microbial changes including the shedding of Clostridium difficile, fec al 13-lactamase activity, and gastrointestinal symptoms were assessed in 51 healthy volunteers given 200 mg of cefixime twice daily for 8 da ys. The number of organisms of the family Enterobacteriaceae (means +/ - standard deviations) dropped from 6.9 +/- 1.1 to 3.9 +/- 1.8 log CFU /g of feces (P < 0.01), whereas counts of enterococci rose from 7.0 +/ - 1.5 to 9.0 +/- 1.0 log CFU/g of feces (P < 0.01). Both counts return ed to their initial levels 50 days after the cessation of treatment. C efixime did not significantly modify the frequency of fecal excretion of Pseudomonas aeruginosa, Staphylococcus spp., yeasts, or members of the Enterobacteriaceae resistant to ceftazidime or ampicillin. The pro portion of subjects shedding C. difficile rose from 6% before treatmen t to 57% (P < 0.01) at the end of treatment but returned to 8% 50 days thereafter. No case of pseudomembranous colitis was observed. Stool c hanges occurred in 13 volunteers during treatment (25%) and in 2 other s more than 10 days after the end of treatment (4%). These changes wer e not significantly associated with the shedding of toxigenic strains of C. difficile or with the presence of toxin A in feces. By contrast, during treatment, stool changes occurred in 8 of the 18 volunteers (4 4%) who had antibiotic activity in their feces but in only 5 of the 33 (15%) for whom no such activity was found (P < 0.05). The absence of antibiotic activity in the feces was itself linked with the presence o f beta-lactamase activity in the feces. Since we had found earlier tha t fecal beta-lactamase activity afforded protection against alteration in stool consistency during treatments with oral cephalosporins, the present study confirmed our previous preliminary results in this respe ct.