Efficacy study demonstrates ciprofloxacin reduces resistant Pseudomonas aeruginosa in non-cystic fibrosis bronchiectasis, suggesting a potential treatment.
Rationale : Ciprofloxacin dry powder for inhalation (DPI) is in Phase III development for chronic intermittent treatment of NCFB. Objective: To assess bactericidal activity of simulated ciprofloxacin DPI against resistant P. aeruginosa isolates through pharmacological studies. Method : Resistant P. aeruginosa isolates (n=24) from NCFB patients with minimum inhibitor concentrations (MIC) ranging from 4 to 64mg/L were evaluated in time kill studies using maximum (120mg/L) or half maximum (60mg/L) sputum concentrations simulating levels expected after inhalation of 32.5mg ciprofloxacin DPI. Efficacy was assessed as reduction in log colony forming units (CFU). A subset of isolates (n=7) were evaluated in a hollow fiber (HF) model to simulate lung pharmacodynamics and determine bactericidal reductions over time. Results : MIC dependent P. aeruginosa CFU reduction rates at maximum concentration ranged from 1 to 6 logCFU and at half maximum from 0.2 to 6 logCFU. A 3 logCFU reduction was observed in isolates with MIC≤32mg/L. In isolates with MIC 64mg/L, a 1 logCFU reduction was observed at maximum concentration. For isolates tested in the HF model, MIC dependent reduction rates were observed; time to display 3 logCFU reduction without regrowth in 10 hours in isolates with MICs from 4 to 8mg/L ranged from 9 to 45 minutes. Conclusion : Sputum concentrations expected after inhalation of 32.5mg ciprofloxacin DPI resulted in bactericidal reduction of resistant P. aeruginosa isolates from NCFB patients. Clinical data in patients with resistant isolates is required to confirm these results.
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Obertegger et al. (2014) studied this question.
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