Influence of cefizoxime alapivoxil on intestinal bacterial flora: A study in gnotibiotic mice inoculated with 4 bacterial strains

We studied the influence of ceftizoxime alapivoxil (CZX-AP), a new prodrug oral cephem agent, on intestinal bacterial flora in gnotobiotic mice inoculated with 4 bacterial strains. We administered 20 mg/kg of CZX-AP once daily for 5 consecutive days to mice inoculated with bacterial strains, Escherichia coli Hokken M, Enterococcus facealis Hokken M, Bacteroides fragilis GKP 0001 and Bifidobacterium breve YIT 4006. We found a decrease in E. coli, but no change in the other 3 bacteria. We also found a decrease in the number of viable E. coli in the contents of each part of the digestive tract (stomach, upper intestine, middle intestine, lower intestine, colon) 4 hours after the last dose was administered, but no change in the other 3 bacteria. This agrees with results we found on changes in the number of fecal flora. All specimens from the stool or digestive tract contents tested for β-lactamase activity before and after drug administration were positive. The minimum inhibitory concentration (MIC) of ceftizoxime (CZX), the active moiety of CZX-AP we used, with inoculum size of 10⁶CFU/mL, was 0.005 μg/mL for E. coli, 12.5 μg/mL for E. facealis, 3.13 μg/mL for B. fragilis and 12.5 μg/mL for B. breve. We found no MIC increase concomitant to drug administration for any bacterial strains.