PFPC Daily - June 24, 2005

Gillespie SH, Basu S, Dickens AL, O'sullivan DM, McHugh TD - "Effect
of subinhibitory concentrations of ciprofloxacin on Mycobacterium
fortuitum mutation rates" J Antimicrob Chemother. 2005 Jun 14; [Epub
ahead of print]

OBJECTIVES: Fluoroquinolones have found a place in the management of
mycobacterial diseases including tuberculosis. It has been previously
shown that subinhibitory concentrations of quinolones increase the
mutation rate in Escherichia coli and staphylococci. The purpose of
this study is to extend this observation to mycobacteria and to
quantify mutation rates.

METHODS: The mutation rate in Mycobacterium fortuitum to
ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, erythromycin
and gentamicin resistance was determined when grown with and without
various sub-MIC concentrations of ciprofloxacin.

RESULTS: M. fortuitum exposed to (1/2) MIC ciprofloxacin had an
increase in the mutation rate of between 72- and 120-fold when
selected on quinolones or other antimycobacterial antibiotics.
Smaller, but significant increases in mutation rate were seen when
the organism was exposed to lower concentrations ((1/4) MIC
and (1/8) MIC).

CONCLUSIONS: These data show that sub-MIC concentrations of
fluoroquinolone significantly increase mutation rates and these data
suggest that care must be taken to ensure that bacteria are not
exposed to subinhibitory concentrations when adding quinolones to a
regimen used to treat mycobacterial infection.