Influence of azithromycin on intestinal bacterial flora

The effect of azithromycin (AZM), an azalide antibiotic, on the intestinal bacterial flora of pediatric patients was investigated in inpatients, and outpatients. There were two boys and three girls, ranging in age from 14 months to 9 years and 2 months with body weights ranging from 9.99 to 24.8 kg. AZM was given orally once daily at dose levels of 10.0 to 19.6 mg/kg for 3 or 5 consecutive days. Stool samples were collected from the patients before, during and after treatment for bacterial isolation and identification, and to determine counts per gram. Stool samples were also analyzed for AZM concentration and assayed for Clostridium difficile D-1 antigen titer. The MICs of AZM for the bacteria isolated were also determined. Although slight variability in flora was noted among the subjects, the counts of Enterobacteriaceae such as Escherichia coli were markedly reduced during and after treatment with AZM in all subjects. Intragenic alternation of Enterococci was observed in some subjects otherwise no significant change was noted in total count of Enterococcus. The cell counts of aerobic bacteria decreased slightly in two patients. The predominant anaerobic bacteria in the intestine such as Bifidobacterium and Bacteroides were slightly decreased in two subjects, but the total anaerobe cell count did not change greatly. There were no abnormal increase in cell counts for glucose non-fermenting gram-negative rods or fungi, but Candida species became the predominant aerobe during treatment in one patient receiving AZM for 5 days. C. difficile and C. difficile D-1 antigen were identified in 3 subjects. There was no relationship between the C. difficile count and stool characteristics. One patient who received AZM for 5 days experienced mild diarrhea. AZM was recovered from stool samples collected from all subjects up to 25 days post-treatment. The AZM concentrations in the stool samples ranged from 0.6 to 2,116.0μg/g. Drug sensitivity testing revealed that the MICs against Enterococcus and Bacteroides isolated from the stool samples became relatively high after treatment. The above results suggest that AZM is excreted in the feces for a long period, but has little influence on the intestinal bacterial flora of pediatric patients.