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Once a parC mutation is
fixed, a profound change occurs in the behavior of the strain with respect to selection of
subsequent resistance mutations. The slide shows the effect of moxifloxacin concentration
on selection of mutants with wild-type cells (open squaqres) and with a parC mutant
(solid squares). The latter displays a much higher MPC and a broad, high plateau. Since
the MIC is not raised very much in the parC mutant, such a strain might be susceptible to
moxifloxacin treatment. However, we would expect moxifloxacin-resistant gyrA
mutants to arise readily. Thus a first-step mutation is likely to accelerate the
development of resistance. This phenomenon is likely to be important because first-step parC
mutants are already widespread but not considered to be levofloxacin-resistant by standard
approaches (7). |