A double-blind, placebo-controlled, parallel group study of oral trovafloxacin on bowel microflora in healthy male volunteers

BACKGROUND: Treatment with oral antibiotic drugs generally influences norma l fecal flora. These changes can be both beneficial (eg, elimination of aer obic, gram-negative bacilli) and detrimental (eg, the appearance of resista nt patho genic micro-organisms). Trovafloxacin, a new fluoroquinolone with in vitro activity against anaerobes, and gram-negative, gram-positive, and atypical pathogens, is a potentially beneficial antimicrobial for bowel ste rilization. This double-blind trial investigated the effect of trovafloxaci n on the normal microbial bowel flora of healthy male subjects. METHODS: Subjects were randomized (in a 2:1 ratio) to receive either 200 mg trovafloxacin once daily for 10 days or a matching placebo. Fecal samples were collected at two baseline occasions, on visit days 4, 7, 10, and 17, a nd at follow-up. Bacterial species were identified and quantified in the fe cal samples. RESULTS: Twelve subjects received the active drug and seven received placeb o. No Enterobacteriaceae were found in samples from days 4 to 10 in subject s receiving trovafloxacin. No changes in Enterobacteriaceae were found thro ughout the study in subjects receiving placebo. Incidental Enterobacteriace ae were isolated from subjects in the trovafloxacin group at the end of the study. No clinically significant differences were found in either group wi th respect to prevalence, appearance, or disappearance of aerobic gram-posi tive cocci, anaerobic bacteria, or yeasts. All tested Enterobacteriaceae we re highly susceptible to trovafloxacin. No increase in minimum inhibitory c oncentration values was seen in day 17 and follow-up samples for isolated E scherichia coli strains. No Clostridium difficile was found in day 17 or fo llow-up samples from subjects in the trovafloxacin group. All tests for clo stridium toxin were negative. CONCLUSIONS: During the treatment period, E. coli could not be cultured fro m the feces of the 12 healthy subjects receiving 200 mg trovafloxacin daily during days 4 to 10. All isolated Enterobacteriaceae were susceptible to t rovafloxacin and no changes in susceptibility were found after the treatmen t period. In subjects treated with trovafloxacin, the prevalence and number of grampositive: bacteria were rapidly reduced. Trovafloxacin is able to s electively and reversibly suppress bowel flora. (C) 1998 by Excerpta Medica , Inc.