Impact of Cefixime on the Normal Intestinal Microflora

Abstract

The ecological effects on the normal intestinal microflora after cefixime tablets in doses of 200 mg twice daily for 7 days were studied in 10 healthy volunteers. Stool specimens were collected before and 2, 4, 7, 14 and 21 days after start of treatment. Plasma samples were collected during 12 h after the first dose on day 1 and 1 sample was taken on day 7 for bioassay of cefixime concentration. Peak plasma concentration of cefixime occurred after about 4 h with a mean of 3.0 mg/l. The mean AUC_0→x after a single dose was estimated at 21.9 mg×h/l and the mean elimination half-life was 3.9 h. The mean plasma concentration of cefixime 3 h after the morning dose on day 7 was 2.0 mg/l. The concentrations of cefixime in faeces increased during treatment. One subject had detectable concentrations in faeces on day 2, three subjects on day 4 and 8 subjects on day 7 in the order of 237–912 mg/kg faeces. There was a marked decrease in the numbers of streptococci and Escherichia coli and an increase in the numbers of enterococci during the administration of cefixime. In the anaerobic microflora, the numbers of cocci, clostridia and bacteroides were suppressed while there were minor changes in the numbers of bifidobacteria. Clostridium difficile was isolated in 5 subjects on day 7 but cytotoxin was only detected in one subject. The intestinal microflora was normalized within 2 weeks after treatment had stopped. Slightly soft stools were reported by 7 subjects. One subject had abdominal pain and diarrhoea 1 week after treatment followed by anal irritation and itching. The present microbiological findings indicate that cefixime has an ecological impact on the human intestinal microflora.