Fluoroquinolone-resistant Streptococcus pneumoniae associated with levofloxacin therapy

Fluoroquinolone-resistant cultures of Streptococcus pneumoniae were isolate d from 2 patients who were treated for pneumonia with levofloxacin. Nucleot ide sequence analysis of bacterial DNA showed that the isolates contained m utations in both parC (DNA topoisomerase IV) and gyrA (DNA gyrase), which w ere shown previously to confer fluoroquinolone resistance. With the resista nt isolates, the MICs for ciprofloxacin, gatifloxacin, grepafloxacin, levof loxacin, and trovafloxacin were above the maximal serum drug concentrations reported for standard dosage regimens. In contrast, the MICs for gemifloxa cin and moxifloxacin were below the maximal serum concentrations. Increased effectiveness at blocking the growth of resistant mutants should make gemi floxacin and moxifloxacin less likely to allow the enrichment of mutants wi thin susceptible populations. Additional resistance mutations in the isolat es were readily obtained by plating on gemifloxacin- or moxifloxacin-contai ning agar. Thus, neither compound is expected to halt further accumulation of resistance mutations once mutant enrichment has been initiated by less p otent derivatives.