Ecological disturbances in intestinal microflora caused by clinafloxacin, an extended-spectrum quinolone.
BACKGROUND
The quinolones developed over the past few years have enhanced in vitro activity and a broader spectrum of antimicrobial activity compared to many other antimicrobial agents including the older quinolones. The present study focuses on the effect of clinafloxacin, a member of the new broad-spectrum quinolone class of antibiotics, on the normal intestinal microflora.


METHODS
A total of 12 healthy volunteers received clinafloxacin orally, 200 mg twice daily for 7 days. Fecal specimens were collected at defined intervals before, during and after the administration in order to study the effect of clinafloxacin on the intestinal microflora and to correlate this effect with fecal clinafloxacin concentrations. Intestinal microorganisms isolated before, during and 2 weeks after clinafloxacin administration were tested for their suseptibility to clinafloxacin.


RESULTS
Oral administration of clinafloxacin resulted in high drug levels in feces (mean value 176.2 mg/kg on day 7) and pronounced ecological disturbances. The aerobic microflora was eradicated in 11 of the 12 subjects and the anaerobic microflora was strongly suppressed during administration. There was a significant emergence of clinafloxacin-resistant Bacteroides spp. strains (MIC > or = 4 mg/ml) during administration. The elevated MIC values still remained 2 weeks after discontinuation of the antibiotic (p < 0.001).


CONCLUSIONS
The emergence of clinafloxacin-resistant Bacteroides spp. demonstrates the necessity of restricting prescription for particular indications in order to preserve the efficacy of the highly active broad-spectrum quinolones.
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Dept of Microbiology, Pathology and Immunology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Nord
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Barkholt
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Hedberg
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Edlund
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D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001439:Bacteroides / Q000187:drug effects; D004352:Drug Resistance, Microbial; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D013997:Time Factors
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C057477:clinafloxacin