Effect of tazobactam/piperacillin on intestinal bacterial flora - Studies in the pediatric field

Tazobactam/piperacillin (TAZ/PIPC), a new injectable combination antibiotic consisting of tazobactam (TAZ), a new β-lactamase inhibitor, and piperacillin (PIPC), an injectable penicillin, in a ratio of 1: 4 (potency) was studied with regard to its effect on the intestinal flora of pediatric patients. Five children with infections (2 boys and 3 girls; ages: 4 months to 9 years 10 months; body weights 8.14-28.0 kg) were given TAZ/PIPC at 43-53.6 mg/kg 4 times daily for 5-15 days. Before, during and after administration, fecal samples were collected and bacterial contents per gram of feces were assessed and viable cells counted for each bacterial species. At the same time, fecal levels of TAZ and PIPC, β-lactamase activity and contents of Clostridium difficle D-1 antigen were also determined. With regards to changes in fecal bacterial flora during administration of TAZ/PIPC, slight individual differences were seen. A decreasing tendency was seen in Enterobacteriaceae among major aerobes in feces. The cell count of this species of bacteria decreased remarkably, falling below the detectable limit in 3 of 5 cases. The cell count of Enterococcus also fell below the detectable limit in 3 of 5 cases. In the 2 remaining cases, changes in bacteria occurred within the genera of the bacterial species examined. As a result, the total cell count of aerobes decreased remarkably in 1 case and slightly in 1 other case. Among anaerobes in feces, Bifidobacterium, Eubacterium and Bacteroides, which had been prevalent, showed a remarkable decrease in cell count during treatment. In 3 cases, the total cell count of anaerobes decreased remarkably. In all 3 of these cases the patients were infants. An increasing tendency was seen in glucose-nonfermentative gram-negative rods, fungi and Bacillus in 1, 4 and 4 cases, respectively, during treatment. In 2 infants in whom remarkable decreases were seen in Enterobacteriaceae, Enterococcus and the main fecal anaerobes, diarrhea was observed, and Candida became the most predominant organism during treatment. C. difficile and C. difficile D-1 antigen were isolated in 1 and 2 cases, respectively, and no relation was found between changes in these counts and fecal characteristics. In 2 cases, TAZ was detected in feces during administration and the fecal concentration ranged from 27.4 to 41.8 μg/g. On the other hand, PIPC was detected in feces during treatment in 3 infants in whom marked changes were seen in the intestinal flora. These cases had fecal concentrations of 34.7 to 238 μg/g. Before treatment, β-lactamase activity was positive in 4 cases. In 3 of these cases, conversion to negativity was obtained during treatment. From these results, TAZ/PIPC is considered to have a marked in fluence on the intestinal flora in childeren. Caution should thus be exercised as the development of diarrhea, along with changes in gastrointestinal bacteria, may occus during the use of TAZ/PIPC.