Effect of S6472 and cefaclor on bacterial flora in adult human feces

S6472 is a mixture of cefaclor (CCL) granules with gastric-soluble coating and those with enteric-soluble coating at the ratio (in potency) of 4 to 6. With administration of this formulation, a prolonged blood level of CCL is obtained. S6472 and CCL were administered orally to 19 healthy male volunteers between 20 and 27 years of age (mean: 23 years) weighing between 51 and 80 kg (mean: 64.7 kg). Four subjects were given 2 capsules and 5 subjects were given 4 capsules each containing 187.5 mg of S6472, 30 minutes after breakfast and supper for 5 days. Five subjects were given 1 capsule and 5 subjects were given 2 capsules each containing 250 mg of CCL 30 minutes after breakfast, lunch and supper for 5 days. The number of fecal bacteria was examined 5 days before the start of administration, the day of the start of administration, 3 and 5 days after the start of administration, and 3, 5 and 10 days after the end of administration. Concentration of CCL in feces and susceptibility of isolated fecal bacteria (at the inoculum size of 10(6) cells/ml) to CCL were examined. Adverse reactions and the effects on laboratory test values were also checked. In 4 subjects receiving 375 mg of S6472 twice a day, the mean population of E. coli was 10(7)-10(9) cells/g feces on all days of observation. There was no effect on the population of Klebsiella sp., Citrobacter sp. Enterobacter sp. and other Enterobacteriaceae. The mean population of all Enterobacteriaceae was 10(8)-10(9) cells/g feces on all days of observation. The population of other Gram-negative bacilli did not show a consistent change, either. There was no effect on the population of Gram-positive bacteria such as Staphylococcus sp., Enterococcus, sp., Micrococcus sp., and of Candida sp. Among anaerobic bacteria, Bacteroides sp. showed the mean population of 10(10) cells/g feces on all days of examination. C. difficile was isolated from 2 subjects out of 4 at the level of 10(2)-10(3) cells/g feces 5 days after the start of administration and 3 days after the end of administration. However, there was no production of toxin in either of the 2 subjects. In another subject, C. difficile was isolated at 10(2)-10(4) cells/g feces with a toxin titre of 10(-3)-10(-4) 3 and 5 days after the start of administration and 10 days after the end of administration. The total population of anaerobic bacteria was 10(10)-10(11) cells/g feces on all days of examination.(ABSTRACT TRUNCATED AT 400 WORDS)