The influence of cefdinir on the intestinal bacterial flora

The influence of cefdinir (CFDN), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFDN in fine granules was administered at a dose of 10mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organism: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable changes were observed in the fecal viable cell counts except that decreases in E. coli counts were observed on the day 3 to 5 after starting administration. The subjects in pediatric study were 7 children with infections, 3 boys and 4 girls, with their ages from 6 months to 12 years 7 months. Their body weights ranged from 5.5 to 29.2 kg. CFDN fine granules was administered at each dose of 3.0 mg/kg to 3.7 mg/kg, 3 times a day for 4 to 14 days. During the administration of CFDN, some variations were observed in the pattern of changes in the fecal bacterial flora between subjects. Although Enterobacteriaceae and total counts of anaerobes were markedly decreased in 2 cases, total counts of aerobes were unchanged in the 2 cases, whereas main aerobes and anaerobes except enterococci hardly varied in the other cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant species sustainingly. Although Clostridium difficile and C. difficile D-l antigens were detected in 1 and 4 cases, respectively, no relationship was found between the number of C. difficile and the characteristics of the feces. With regard to the drug sensitivities of bacteria isolated from feces before and after administration of CFDN, higher levels of resistance were found in some bacteria such as Enterococcus and Bacteroides during or after administration than before administration. CFDN was detected in fecal samples from 2 cases during administration with concentrations ranging between 0.99∼254 μg/g. High value of CFDN was found in a case with low β-lactamase activity in feces, in which marked decrease of Enterobacteriaceae and total counts of anaerobes was observed. The above results suggest that CFDN is considered to be a drug with relatively small influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, our attention will be required. Particular care is also required for the occurrence of diarrhea and microbial replacement during continuous, long-term administration of the drug.