In-vitro susceptibilities of Pseudomonas aeruginosa and Pseudomonas spp. to the new fluoroquinolones clinafloxacin and PD 131628 and nine other antimicrobial agents

Abstract

The in-vitro activities of two new fluoroquinolones, clinafloxacin (CI-960, PD 127391, AM-1091) and PD 131628 (the active component of the pro-drug CI-990, PD 131112) and nine other antibiotics were tested against 107 clinical isolates of Pseudomonas aeruginosa. 12 isolates of Xanthomonas maltophilia. and 19 isolates of other Pseudomonas spp. Of the 107 P. aeruginosa isolates, 33 were resistant to gentamicin, tobramycin and amikacin, 17 were resistant to only one or two of these aminoglycosides and 24 were aminoglycoside sensitive. Thirty-three were isolates from cystic fibrosis patients. Susceptibility studies were performed using the agar dilution technique and kinetic time kill curves. With the exception of aminoglycoside-sensitive P. aeruginosa isolates where ciprofloxacin had similar activity to cinafloxacin and PD 131628, the two new fluoroquinolones were the most active agents against all isolates tested (MIC₉₀ 0·25–2·0 mg/L). Cross-resistance was identified with ciprofloxacin and ofloxacin-resistant strains, but the superior activity of clinafloxacin and PD 131628 resulted in 90% of the isolates having MICs < 2 mg/L. Kinetic kill curves with aminoglycoside-sensitive P. aeruginosa revealed ciprofloxacin to have the most rapid and sustained killing. However, with amino glycoside-resistant P. aeruginosa isolates, clinafloxacin and PD 131628 were more rapidly bactericidal than ciprofloxacin.