Impact of ticarcillin/clavulanate on the intestinal microflora.

Ten healthy volunteers were given 5.2 g Timentin (5 g ticarcillin plus 0.2 g clavulanate by intravenous bolus three times daily for seven days. Stool specimens were collected before and 2, 3, 5, 7, 14 and 21 days after the start of treatment to study the effect on the normal intestinal microflora. The concentrations of ticarcillin and clavulanate in serum, urine and faeces were determined by a microbiological method and the pharmacokinetics were studied on days 1, 3 and 7. There were no significant differences in the serum concentrations of ticarcillin and clavulanate during the three days. The total 8-h recovery in urine of ticarcillin was 62% of the dose and of clavulanate 19%. The mean serum half-life of ticarcillin was 1.0 h and of clavulanic acid 0.91 h. There were no measurable concentrations of ticarcillin or clavulanate in the faecal specimens. The number of enterobacteria slightly decreased, while there was a minor increase in the number of enterococci and streptococci during the administration of ticarcillin/clavulanate. The anaerobic microflora was also slightly affected. There was a minor decrease in the number of anaerobic cocci, bifidobacteria, eubacteria, lactobacilli and clostridia, but the number of bacteroides was not influenced by the treatment. After treatment the aerobic and anaerobic microflora returned to normal in all volunteers. The present microbiological findings indicate that ticarcillin/clavulanate has a minor ecological impact on the human intestinal microflora.