JAC Advance Access published online on September 1, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg418
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Antimicrobial Agents Research Group, Division of Immunity
and Infection, The Medical School, University of Birmingham, Birmingham
B15 2TT, UK
* Corresponding author. E-mail: l.j.v.piddock{at}bham.ac.uk.
Received 21 May 2003
; revised 11 July 2003
; accepted 16 July 2003
Objectives: Garenoxacin is a novel
des-F(6)-quinolone with good anti-anaerobe activity. The accumulation of
garenoxacin and five other quinolones in the presence and absence
of a variety of efflux pump inhibitors, including carbonyl cyanide m-chlorophenyl hydrazone (CCCP: 100 µM),
verapamil (25 µM), reserpine
(20 mg/L), sodium orthovanadate (50 µM)
and Phe-Arg- Methods: Bacteroides fragilis was
grown in Wilkins Chalgren broth (Oxoid Ltd, UK) in a MKII anaerobic
workstation (Don Whitley, Shipley, UK). Susceptibility testing was
performed, according to the agar doubling dilution method, using
Wilkins Chalgren agar supplemented with 5% horse blood.
A fluorometric assay was used to measure the accumulation of quinolones
(10 mg/L) by B. fragilis. Results: The activity of the agents for B.
fragilis NCTC 9343/ATCC 25285 was clinafloxacin > garenoxacin > levofloxacin = gatifloxacin > moxifloxacin > ciprofloxacin.
A weak correlation was observed between the molecular size of the
free form and the MIC, the steady state concentration (SSC) and
the initial rate of accumulation, but not for the hydrophobicity
of each agent. In the presence of reserpine, the SSC of all agents increased.
The addition of CCCP had no effect upon garenoxacin or clinafloxacin
accumulation, but significantly increased the SSC of ciprofloxacin,
moxifloxacin, gatifloxacin and levofloxacin. Verapamil increased the
SSC of garenoxacin, whereas sodium orthovanadate had no effect on
the concentration of accumulated garenoxacin. Conclusions: These data suggest that there is
probably more than one type of efflux pump in B. fragilis that exports
quinolones.
Keywords: efflux pump inhibitors, antibiotic accumulation,
quinolones
Accumulation of garenoxacin by Bacteroides
fragilis compared with that of five fluoroquinolones
-naphthylamide (MC-207110)
(20 mg/L) was investigated.
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