Delafloxacin activity against fluoroquinolone-resistant Pseudomonas aeruginosa: in vitro activity and mutant prevention concentration

Introduction Pseudomonas aeruginosa frequently develops resistance to fluoroquinolones limiting the usefulness of these agents for the treatment of healthcare-associated infections. This study evaluated the in vitro activity of delafloxacin in comparison with the older-generation fluoroquinolones against clinical P. aeruginosa isolates, and explored its potential to suppress the selection of resistant subpopulations. Methods One hundred clinical isolates were tested against ciprofloxacin, levofloxacin, and delafloxacin by broth microdilution method. Susceptibility was interpreted according to EUCAST criteria for ciprofloxacin and levofloxacin and FDA criteria for delafloxacin. Mutant prevention concentrations (MPCs) were determined for the three fluoroquinolones in 12 selected isolates using a high-inoculum agar-based method. Results Resistance was observed in 29% of isolates for both ciprofloxacin and levofloxacin, compared with 25% for delafloxacin. Among isolates resistant to both ciprofloxacin and levofloxacin, 32.0% were susceptible or intermediate to delafloxacin. The median MPC/MIC ratio was 4 (IQR, 4–8) for delafloxacin, compared with 8 (IQR, 7–16) for ciprofloxacin and 16 (IQR, 7–64) for levofloxacin. Discussion Overall, delafloxacin retained in vitro activity against a subset of fluoroquinolone-resistant P. aeruginosa isolates and showed a favorable mutant prevention profile in the isolates tested, with a lower median MPC/MIC ratio than ciprofloxacin and levofloxacin. These findings provide preliminary evidence supporting further investigation of delafloxacin against fluoroquinolone-resistant P. aeruginosa .