JAC Advance Access published online on July 12, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl278
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1 Greater Los Angeles Veterans Administration Healthcare Systems, 691/151J, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA; Department of Medicine, University of California, Los Angeles, CA 90024, USA
* To whom correspondence should be addressed. Objectives: The aim of the present study was to determine correlation between bmeB efflux pump overexpression and resistance to fluoroquinolones and Methods: Susceptibility to garenoxacin, levofloxacin, moxifloxacin, cefoxitin and faropenem ± EPIs (CCCP, MC-207,110, reserpine and verapamil) was determined. Expression of bmeB efflux pumps was measured, topoisomerase genes were sequenced and Results: Isolates were grouped into categories based on susceptibility patterns, topoisomerase sequence and efflux pump expression. Panel I isolates (19/51, 37.3%) were highly resistant to fluoroquinolones and cefoxitin (resistance to all agents was significantly reduced by EPIs, P < 0.05), had a point mutation in gyrA (C Conclusions: These data suggest that bmeB efflux pump overexpression can (i) cause low- to intermediate-level clinically relevant fluoroquinolone resistance; (ii) be coupled with GyrA substitutions to cause high-level fluoroquinolone resistance; (iii) contribute to high-level clinically relevant resistance to
Received March 8, 2006
Accepted June 8, 2006
Original article
Clinical significance of overexpression of multiple RND-family efflux pumps in Bacteroides fragilis isolates
Lilian Pumbwe 1,
Abraham Chang 2,
Rachel L. Smith 2,
and
Hannah M. Wexler 1 *
2 Greater Los Angeles Veterans Administration Healthcare Systems, 691/151J, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA
Hannah M. Wexler, E-mail: hwexler{at}ucla.edu
Abstract 
-lactams in Bacteroides fragilis clinical isolates (n = 51) and the effects of broad-spectrum efflux pump inhibitors (EPIs) on the MICs of the test antibiotics.-lactamase production was determined.
T) causing a Ser-82Phe substitution, and overexpressed bmeB4 and bmeB15. Panel II isolates (7/51; 13.7%) had intermediate-level resistance to fluoroquinolones and cefoxitin and a GyrA substitution. Panel IIIA isolates (21/51; 41.2%) had intermediate-level fluoroquinolone resistance and high-level cefoxitin resistance [resistance to all agents was significantly reduced by EPIs (P < 0.05)] and overexpressed bmeB4 and bmeB15. Panel IIIB isolates (4/51; 7.8%) had low-level fluoroquinolone resistance and high-level resistance to cefoxitin [cefoxitin resistance was significantly reduced by EPIs (P < 0.05)] and overexpressed bmeB4, bmeB6, bmeB10 and bmeB14. All isolates were -lactamase-positive.-lactams.
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