Do the differing antimicrobial agents have different mechanisms responsible for resistance?
The levofloxacin mechanism of action is via binding of topoisomerase IV, whereas moxifloxacin preferentially binds DNA gyrase. Since most first-step pneumococcal mutants have alterations in the parC gene of topoisomerase IV it was proposed that moxifloxacin may be less likely to develop resistance. However, this has not been shown to be the case. A recent study investigated 4 S. pneumoniae isolates: a wild type, 2 first-step parC mutants, and a pump mutant. Analysis of time kill curves demonstrated that moxifloxacin and levofloxacin displayed similar rates and extent of bacterial kill for the wild type, efflux pump type, and parC mutant (78).
Researchers have calculated concentrations that inhibit mutation with a study investigating three fluoroquinolone-susceptible and five fluoroquinolone-resistant S. pneumoniae isolates which were exposed to one, two, four, eight, and sixteen times the MICs of ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin. MPCs were evaluated. Results indicated that levofloxacin, gatifloxacin, and moxifloxacin were more able to prevent the development of resistance by fluoroquinolone-susceptible isolates, isolates that are efflux positive, or isolates that carry a GyrA mutation (72).