JAC Advance Access published online on November 12, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg480
© 2003 by The British Society for Antimicrobial Chemotherapy
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Brief report
1 Public Health Research Institute, 225 Warren Street, Newark,
NJ 07103, USA
* Corresponding author. E-mail: drlica{at}phri.org.
Received 9 May 2003
; revised 10 September 2003
; accepted 25 September 2003
Objectives: To examine the effect
of first-line and second-line anti-tuberculosis agents on the ability
of fluoroquinolones to kill mycobacteria. Methods: A clinical isolate of Mycobacterium
tuberculosis and a laboratory strain of Mycobacterium
smegmatis were grown in liquid medium and treated with a fluoroquinolone
in the presence or absence of anti-tuberculosis agents. Bacterial
survival was determined by viable colony counts on agar medium. Results: When moxifloxacin activity was examined
in two-drug combinations containing traditional anti-tuberculosis
agents, activity was greater than either compound alone with isoniazid,
capreomycin and low, but not high, concentrations of rifampicin.
Cycloserine contributed no additional activity, and ethambutol interfered
with the lethal action of moxifloxacin and gatifloxacin. Experiments
with M. smegmatis confirmed that
both rifampicin and ethambutol reduce fluoroquinolone lethality.
Moreover, ethambutol increased the recovery of fluoroquinolone-resistant
mutants newly created by ethyl methanesulphonate treatment. Conclusions: The intrinsic bactericidal activity
of C-8-methoxy fluoroquinolones can be adversely affected by some
agents currently used for treatment of tuberculosis.
Keywords: moxifloxacin, gatifloxacin, rifampicin, ethambutol
In vitro activity of C-8-methoxy
fluoroquinolones against mycobacteria when combined with anti-tuberculosis
agents
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