Effect Of Biapenem(L-627) On Fecal Flora In Gnotobiotic Mice And Children

Biapenem (L-627), a novel injectable carbapenem antibiotic, was studied with regard to its effect on mice inoculated with four types of bacteria and on the intestinal flora of pediatric patients. L-627 was given i.m., 40mg/kg once daily for 5 consecutive days, to mice inoculated enterically with four types of bacteria (Escherichia coli, Enterococcus faecalis, Bacteroides fragilis, and Bifidobacterium breve). Except for a mild decrease in E. coli, there were no major fluctuations in viable bacterial counts in the feces during the treatment. Five children with bacterial infections (3 boys and 2 girls; ages: 1 month to 7 years and 7 months; body weights 4.62~21.8 kg) were given L-627 at 6.0 to 11.7 mg/kg 3 times daily for 7 to 11 days. Among aerobes, although Enterobacteriaceae such as E. coli tended to decrease remarkably in all patients, there was no major change in Enterococcus. Consequently, total aerobe counts did not change significantly in any patient. Among anaerobes, Bifidobacterium, Bacteroides, and Eubacterium, which are the predominant organisms in infants, decreased remarkably in some patients. One of the patients showed a marked decrease in total anaerobe count associated with a change in fecal characteristics (diarrhea). Glucose nonfermenting Gram-negative bacilli or fungi did not become predominant organisms in any patient. Recovery from these changes in the intestinal flora was noted promptly after terminating L-627 treatment. L-627 was detected in the feces of 4 patients during treatment. The fecal concentration ranged from 0.24 to 2.22μg/g. Clostridium difficile was not detected in any patient. Although C. difficile D-l antigen was observed in 2 patients, it bore no relationship to fecal properties. The results indicated that L-627 had relatively few effects on the intestinal flora compared to other new β-lactam antibiotics.