Ecological impact of the des-F(6)-quinolone, BMS-284756, on the normal intestinal microflora.
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.


CONCLUSIONS
The ecological impact of BMS-284756 is selective, with results similar to those described for other quinolones.
Nord
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CE
Department of Microbiology, Pathology and Immunology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. carl.erik.nord@impi.ki.se
Gajjar
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DA
Grasela
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D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology*; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007211:Indoles; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010919:Placebos; D015363:Quinolones
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D007211:Indoles; D010919:Placebos; D015363:Quinolones; C419689:garenoxacin