C E Nord1, D A Gajjar, D M Grasela. 1. Department of Microbiology, Pathology and Immunology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. carl.erik.nord@impi.ki.se
Abstract
OBJECTIVE:BMS-284756 (T-3811ME) is a novel des-F(6)-quinolone effective against a broad spectrum of aerobic and anaerobic pathogens. The aim of this study was to investigate the ecological effect of BMS-284756 on the intestinal microflora. METHODS:Forty healthy subjects participated in the trial. Eight subjects were assigned to each of five dose panels (100, 200, 400, 800 and 1200 mg BMS-284756) and received daily oral dosing with either BMS-284756 (n = 6) or placebo (n = 2) for 14 days. Fecal samples were collected before (days -2 and -1), during (days 7 and 14), and after (days 21, 28, and 45) completion of the administration period. RESULTS: In subjects receiving 100 or 200 mgBMS-284756, no significant changes in the intestinal aerobic and anaerobic microflora occurred. The number of enterococci, bacilli, corynebacteria, bifidobacteria, lactobacilli, clostridia and bacteroides decreased in subjects receiving 400 or 800 mg BMS-284756, whereas the number of eubacteria increased. Subjects who received 1200 mg BMS-284756 had significant changes in the microflora: enterococci, bacilli, corynebacteria, enterobacteria, bifidobacteria, lactobacilli, clostridia and bacteroides were suppressed, whereas eubacteria and yeasts were increased. Regardless of dose, the microflora returned to normal levels at day 28 (2 weeks after the administration of BMS-284756 was discontinued). Fecal concentrations of BMS-284756 increased with the higher doses, from 35.7 mg/kg (100 mg) to 262.8 mg/kg (1200 mg). These ecological findings should be considered if 800- or 1200-mg doses of BMS-284756 are to be used for longer periods than 14 days. CONCLUSION: The ecological impact of BMS-284756 is selective, with results similar to those described for other quinolones.
RCT Entities:
OBJECTIVE: BMS-284756 (T-3811ME) is a novel des-F(6)-quinolone effective against a broad spectrum of aerobic and anaerobic pathogens. The aim of this study was to investigate the ecological effect of BMS-284756 on the intestinal microflora. METHODS: Forty healthy subjects participated in the trial. Eight subjects were assigned to each of five dose panels (100, 200, 400, 800 and 1200 mg BMS-284756) and received daily oral dosing with either BMS-284756 (n = 6) or placebo (n = 2) for 14 days. Fecal samples were collected before (days -2 and -1), during (days 7 and 14), and after (days 21, 28, and 45) completion of the administration period. RESULTS: In subjects receiving 100 or 200 mg BMS-284756, no significant changes in the intestinal aerobic and anaerobic microflora occurred. The number of enterococci, bacilli, corynebacteria, bifidobacteria, lactobacilli, clostridia and bacteroides decreased in subjects receiving 400 or 800 mg BMS-284756, whereas the number of eubacteria increased. Subjects who received 1200 mg BMS-284756 had significant changes in the microflora: enterococci, bacilli, corynebacteria, enterobacteria, bifidobacteria, lactobacilli, clostridia and bacteroides were suppressed, whereas eubacteria and yeasts were increased. Regardless of dose, the microflora returned to normal levels at day 28 (2 weeks after the administration of BMS-284756 was discontinued). Fecal concentrations of BMS-284756 increased with the higher doses, from 35.7 mg/kg (100 mg) to 262.8 mg/kg (1200 mg). These ecological findings should be considered if 800- or 1200-mg doses of BMS-284756 are to be used for longer periods than 14 days. CONCLUSION: The ecological impact of BMS-284756 is selective, with results similar to those described for other quinolones.