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 normal fecal flora. These changes can be both beneficial (eg, elimination of aerobic, gram-negative bacilli) and detrimental (eg, the appearance of resistant pathogenic 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 sterilization. This double-blind trial investigated the effect of trovafloxacin 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, and at follow-up. Bacterial species were identified and quantified in the fecal samples. RESULTS: Twelve subjects received the active drug and seven received placebo. No Enterobacteriaceae were found in samples from days 4 to 10 in subjects receiving trovafloxacin. No changes in Enterobacteriaceae were found throughout the study in subjects receiving placebo. Incidental Enterobacteriaceae were isolated from subjects in the trovafloxacin group at the end of the study. No clinically significant differences were found in either group with respect to prevalence, appearance, or disappearance of aerobic gram-positive cocci, anaerobic bacteria, or yeasts. All tested Enterobacteriaceae were highly susceptible to trovafloxacin. No increase in minimum inhibitory concentration values was seen in day 17 and follow-up samples for isolated Escherichia coli strains. No Clostridium difficile was found in day 17 or follow-up samples from subjects in the trovafloxacin group. All tests for clostridium toxin were negative. CONCLUSIONS: During the treatment period, E. coli could not be cultured from the feces of the 12 healthy subjects receiving 200 mg trovafloxacin daily during days 4 to 10. All isolated Enterobacteriaceae were susceptible to trovafloxacin and no changes in susceptibility were found after the treatment period. In subjects treated with trovafloxacin, the prevalence and number of gram-positive bacteria were rapidly reduced. Trovafloxacin is able to selectively and reversibly suppress bowel flora.