Influence of S-1108 on intestinal bacterial flora

The effect of S-1108, a new oral cephem antibiotic, on intestinal bacterial flora was studied in tetra-contaminated mice and pediatric patients. S-1108 in a fine granular form was administred at a dose of 15 mg/kg once a day for 5 consecutive days to mice infected with Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. The viable fecal bacterial cell count of each of these 4 species of bacteria was slightly reduced in 5 days after the start of the drug administration. Five boys (weighing 12.0 to 42.0 kg) with bacterial infections were entered into this pediatric study. Their ages ranged from 2 years 4 months to 9 years 3 months. S-1108 (fine granules) was administered at a dose of 2.3 to 6.0 mg/kg, 3 times a day for 5 to 11 days. Cell counts of primary aerobes, anaerobes and total anaerobic cells decreased markedly in three patients, but in the remaining two patients the total number of aerobic and anaerobic cells did not change appreciably. Glucose-nonfermentating Gram-negative rods did not become predominant during the period of S-1108 administration. Candida became predominant in the three patients in whom the other bacteria had markedly decreased. Counts of predominant aerobic and anaerobic bacteria decreased markedly during the regimen in 3 out of 5 cases. S-1006 was detected in stools of the 3 cases at concentrations ranging from 235 to 516 μg/g during the administration of S-1108. Intestial bacteria that produce β-lactamase were not present in the feces of any of the patients. Based on these results, S-1108 (fine granules) appears to have relatively little effect on intestinal bacterial flora similarly to other new oral cephems. Because of individual differences, however, the drug may be excreted in the feces at high concentrations, and this would result in changes in intestinal bacterial flora. Therefore, attention must be given to fecal drug concentrations.