Mutant prevention concentration as a measure of fluoroquinolone potency against mycobacteria

Mutant prevention concentration (MPC) has been proposed as a new measure of antibiotic potency by which the ability to restrict selection of resistant mutants is evaluated. To determine whether MPC provides potency informatio n unavailable from the more customary measurement of the MIG, 18 fluoroquin olones were examined for their ability to block the growth of Mycobacterium smegmatis and to select resistant mutants from wild-type populations. Both MPC and MIC were affected by changes in the moiety at the fluoroquinolone C-8 position and in alkyl groups attached to the C-7 piperazinyl ring. When eight resistant mutants, altered in the gyrase A protein, were tested with fluoroquinolones having either a methoxy or a hydrogen at the C-8 position , the MIC for the most resistant mutant correlated better with the MPC than did the MIC for wild-type cells. For C-8-fluorine derivatives, which were generally less active than the C-8-methoxy compounds but which were more ac tive than C-8-hydrogen derivatives, the MICs for both the mutant and the wi ld type correlated well,vith the MPCs. Thus, measurement of the MICs for wi ld-type cells can reflect the ability of a quinolone to restrict the select ion of resistance, but often it does not. With the present series of compou nds, the most potent contained a C-l-methoxy and a small group attached to the C-7 ring.