Effect of tazobactam/piperacillin on intestinal bacterial flora: Studies in mice inoculated with four types of bacteria

Tazobactam/piperacillin (TAZ/PIPC), an injectable combination antibiotic consisting of tazobactam (TAZ), a new β-lactamase inhibitor, with piperacillin (PIPC), an injectable penicillin antibiotic, in a ratio of 1: 4 (potency) was studied with regard to its effect on the intestinal flora of mice inoculated with four types of bacteria. A comparison was made with the efficacy of PIPC alone. In mice inoculated with four species of bacteria (Escherichia coli, Kitaken M, Enterococcus faecalis, Kitaken M, Bacteroides fragilis GKP 0001, and Bifidobacterium breve YIT 4006) in the intestinal lumen, TAZ/PIPC was administered i. m. at 100 mg/kg once daily for 5 consecutive days. From the day after the beginning of treatment, the cell counts of all species of bacteria examined began to decrease, and from the third day thereafter the cell counts were below detectable limits except for E. faecalis. Comparable results were obtained when PIPC alone at 100 mg/kg was administered in a similar manner. At 4 hours after completion of the final dose, the viable cell counts in the contents of various segments of the gastrointestinal tract (stomach, upper, middle and lower intestine, and large intestine) were lower for groups treated with TAZ/PIPC or PIPC than the control group for all segments examined. The PIPC levels in feces from the day after the beginning of treatment, and thereafter in large intestinal contents upon completion of the final dose, were 8.30-75.3 μg/g for the TAZ/PIPC group (excluding one sample in which the PIPC level was below the detectable limit) and 3.62-32.4 μg/g for the PIPC group (excluding one sample in which the PIPC level was below the detectable limit). The PIPC level in gastrointestinal contents was highest in the middle and lower segments of the intestine for both the TAZ/PIPC and the PIPC group. No detectable amount of TAZ was found in feces or in the gastrointestinal contents of each segment, with the exception of 2 samples. The minimum inhibitory concentrations (MIC) of TAZ/PIPC and PIPC were 6.25 μg/ml and 3.13 μg/ml for E. coli kitaken M, 3.13-6.25 μg/ml and 3.13 μg/ml for E. faecalis Kitaken M, 0.78-1.56 μg/ml and 3.13 μg/ml for B. fragilis GKP 0001, and 0.78 μg/ml and 0.39 μg/ml for B. breve YIT 4006. Neither the TAZ/PIPC nor the PIPC dosing group showed an increasing effect on the MIC of the 4 species tested.