In Vitro Killing of Gram-Negative Bacilli Using Ciprofloxacin Based on Dry Powder Inhaled Drug Concentrations

Background: Inhaled drug formulations are reported to deliver high airway pulmonary drug concentrations with minimal systemic adverse effects. High drug concentrations with fluoroquinolones are desirable as they are concentration-dependent antibacterial agents. Methods: We exposed drug-susceptible strains of Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa to the measured minimum inhibitory and mutant prevention drug concentrations and to the mean reported pulmonary drug concentrations of ciprofloxacin in vitro by incubation in 3 h and 24 h kill assays. Results: Using 105 cfu/mL in the 3 h kill assay, ciprofloxacin at a 409 µg/mL pulmonary drug concentration killed 89.6 (1.4 log10)–99.9% (4.4 log10) of cells across all tested species following 5 min of drug exposure. For 106–109 cfu/mL in the 24 h kill assay, ciprofloxacin at 409 µg/mL killed 93.6 (1.3 log10)–99.7% (2.7 log10) of P. aeruginosa cells following 6 h of drug exposure across all bacterial densities; 97.4 (1.3 log10)–100% (6.4 log10) of E. coli, 99.4 (2.9 log10)–99.9% (5.9 log10) of E. cloacae and 98.7 (2.1 log10)–100% (7.5 log10) of K. pneumoniae following 24 h of drug exposure. Conclusions: The ciprofloxacin pulmonary drug concentration was bactericidal over all bacterial densities with the high drug concentration rapidly reducing viable bacterial cells. Clinical correlation of these in vitro observations is warranted. Additionally, in vitro testing using the drug powder formation may further validate these observations.