Antimicrobial activity of NM 394, an active form of prulifloxacin, against clinical isolates of Pseudomonas aeruginosa with a type II topoisomerase mutation

We examined mutations int he quinolone-resistance-determining regions (QRDR) of gyrA and parC genes in 77 clinical isolates of Pseudomonas aeruginosa and compared the susceptibility of these isolates to NM 394, an active form of the prodrug prulifloxacin, with those to ciprofloxacin (CPFX), levofloxacin (LVFX), and gatifloxacin (GFLX). Of the 77 strains, 24 isolates exhibited an amino acid replacement in the GyrA or both the GryA and ParC regions as a result of mutations in gyrA or both gyrA and parC, respectively. All of the 24 isolates had amino acid replacements in GyrA; none of the strains had amino acid replacements restricted to ParC. Amino acid replacement in GyrA but not in ParC was found in 6 isolates whose susceptibility to NM 394 was decreased; the susceptibility of these 6 isolates to CPFX, LVFX and GFLX were also decreased. Amino acid replacement in GyrA and ParC was found in 18 isolates that were highly resistant to NM 394, LVFX, CPFX and GFLX. The short-term bactericidal activity of NM 394 at the MIC concentration against strains with or without amino acid replacement in GyrA or both GyrA and ParC was similar. The short-term bactericidal activities of CPFX and LVFX against strains with amino acid replacements in GyrA or both GyrA and ParC were lower than those against the strains with no amino acid replacements. These results demonstrate that the bactericidal activity of NM 394 against strains with a mutation in their type II topoisomerase genes was higher than those of CPFX and LVFX.