Shedding of Clostridium difficile, fecal beta-lactamase activity, and gastrointestinal symptoms in 51 volunteers treated with oral cefixime

Abstract

Microbial changes including the shedding of Clostridium difficile, fecal 1-lactamase activity, and gastrointestinal symptoms were assessed in 51 healthy volunteers given 200 mg of cefixime twice daily for 8 days. 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 returned to their initial levels 50 days after the cessation of treatment. Cefixime 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 proportion of subjects shedding C. difficile rose from 6% before treatment 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 changes occurred in 13 volunteers during treatment (25%) and in 2 others more than 10 days after the end of treatment (4%).These changes were 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 (44%) 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 of 13-lactamase activity in the feces. Since we had found earlier that fecal 1-lactamase activity afforded protection against alteration in stool consistency during treatments with oral cephalosporins, the present study confirmed our previous preliminary results in this respect.

Sensitive Quantification of Clostridium difficile Cells by Reverse Transcription-Quantitative PCR Targeting rRNA Molecules

“…Analysis of the toxin gene type showed that 8 (50%) of the 16 isolates were positive for tcdA and tcdB and that the other half lacked tcdA and tcdB (see Table S2 in the supplemental material ["First test" column]), although all the specimens were negative in the EIA (Table 2). Because the sensitivity of the EIA was not as high as 10 6 CFU/g of feces, the incidence of toxigenic strains might have been underestimated. The precise environmental signals modulating toxin expression remain unclear, but in vitro studies indicate that toxin expression may be enhanced by stressors, including antibiotics, catabolite repression, and sporulation (18,53).…”

“…This organism has been reported to be carried asymptomatically by 0% to 15% of healthy adults (10,11,20,36,37) and by 13% to 26% of hospitalized patients (30,31,42,52). C. difficile forms metabolically dormant spores to survive in unfavorable environments, such as conditions of aerobiosis, nutrient deficiency, dryness, or high temperature (16,22,54).…”

Antibiotikainduzierte Diarrhö und pseudomembranöse Enterokolitis

“…Chachaty et al [43] konnte bei 51 gesunden Probanden, die über 8 Tage 2-mal täglich Cefixime erhielten, eine Zunahme von Clostridium-difficile-Nachweisen von 6 auf 57% und ein Rückgang auf 8% 50 Tage nach Absetzen der Antibiotikagabe zeigen.…”

Transfer of Plasmid-Mediated CTX-M-9 from Salmonella enterica Serotype Virchow to Enterobacteriaceae in Human Flora-Associated Rats Treated with Cefixime

“…According to the pharmacokinetic study of cefixime in rats, the bioavailability of cefixime was estimated at 30% (data not shown) and comparable to the rat and human data previously described (18,39), so the part excreted in the gastrointestinal tract may be considered approximately 70%. Based on these observations, we hypothesized that cefixime was hydrolyzed during transit by the ␤-lactamases-producing strains of anaerobic endogenous flora as previously described (11,26,42). We evaluated the impact of these ␤-lactamases by treating animals with cefixime together with clavulanic acid.…”