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Antimicrobial Agents and Chemotherapy, September 1999, p. 2251-2255, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Fluoroquinolone Resistance in Bacteroides fragilis following Sparfloxacin Exposure

M. L. Peterson,1,2 L. B. Hovde,2 D. H. Wright,1,2 A. D. Hoang,1,2 J. K. Raddatz,1,2,dagger P. J. Boysen,2 and J. C. Rotschafer1,2,*

College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455,1 and Antibiotic Pharmacodynamic Modeling Institute, Regions Hospital, St. Paul, Minnesota 551012

Received 29 October 1997/Returned for modification 21 February 1998/Accepted 14 June 1999

In vitro pharmacodynamic studies investigating the antimicrobial properties of five fluoroquinolones, (trovafloxacin, sparfloxacin, clinafloxacin, levofloxacin, and ciprofloxacin) against Bacteroides fragilis ATCC 23745 were conducted. The times required to reduce the viable counts by 3 log units were as follows: clinafloxacin, 2.9 h; levofloxacin, 4.6 h; trovafloxacin, 6 h; and sparfloxacin, 10 h. Exposure to ciprofloxacin did not achieve a 3-log decrease in viable counts. The susceptibility of B. fragilis was determined both prior to exposure and following 24 h of exposure to each of the five fluoroquinolones tested. The MICs of clinafloxacin, levofloxacin, trovafloxacin, sparfloxacin, ciprofloxacin, metronidazole, cefoxitin, chloramphenicol, and clindamycin were determined by the broth microdilution method. The MICs for B. fragilis preexposure were as follows: clinafloxacin, 0.25 µg/ml; trovafloxacin, 0.5 µg/ml; sparfloxacin, 2 µg/ml; levofloxacin, 2 µg/ml; and ciprofloxacin, 8 µg/ml. Similar pre- and postexposure MICs were obtained for cultures exposed to trovafloxacin, clinafloxacin, levofloxacin, and ciprofloxacin. However, following 24 h of exposure to sparfloxacin, a fluoroquinolone-resistant strain emerged. The MICs for this strain were as follows: clinafloxacin, 1 µg/ml; trovafloxacin, 4 µg/ml; sparfloxacin, 16 µg/ml; levofloxacin, 16 µg/ml; and ciprofloxacin, 32 µg/ml. No changes in the susceptibility of B. fragilis pre- and postexposure to sparfloxacin were noted for metronidazole (MIC, 1 µg/ml), cefoxitin (MIC, 4 µg/ml), chloramphenicol (MIC, 4 µg/ml), and clindamycin (MIC, 0.06 µg/ml). Resistance remained stable as the organism was passaged on antibiotic-free agar for 10 consecutive days. Mutant B. fragilis strains with decreased susceptibility to clinafloxacin, trovafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were selected on brucella blood agar containing 8× the MIC of levofloxacin at a frequencies of 6.4 × 10-9, 4× the MICs of trovafloxacin and sparfloxacin at frequencies of 2.2 × 10-9 and 3.3 × 10-10, respectively, and 2× the MIC of clinafloxacin at a frequency of 5.5 × 10-11; no mutants were selected with ciprofloxacin. The susceptibilities of strains to trovafloxacin, levofloxacin, clinafloxacin, sparfloxacin, and ciprofloxacin before and after exposure to sparfloxacin were modestly affected by the presence of reserpine (20 µg/ml), an inhibitor of antibiotic efflux. The mechanism of fluoroquinolone resistance is being explored, but it is unlikely to be efflux due to a lack of cross-resistance to unrelated antimicrobial agents and to the fact that the MICs for strains before and after exposure to sparfloxacin are minimally affected by reserpine.

* Corresponding author. Mailing address: Department of Clinical Pharmacy, Regions Hospital, 640 Jackson St., St. Paul, MN 55101. Phone: (651) 221-3896. Fax: (651) 292-4031. E-mail: rotsc001{at}maroon.tc.umn.edu.

dagger Present address: Value Rx, Plymouth, MN 55442-2599.

Antimicrobial Agents and Chemotherapy, September 1999, p. 2251-2255, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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