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Background: Colistin often remains the only active agent against multidrug-resistant Gram-negative pathogens. The aim of the study was to assess efficacy of nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii., Methods: One hundred and sixty-five patients with VAP caused by P. aeruginosa and A. baumannii were enrolled in a prospective, observational, and comparative study. The sensitive strain group included 122 patients with VAP caused by P. aeruginosa and A. baumannii susceptible to β-lactams, aminoglycosides, or quinolones and treated with intravenous antibiotics for 14 days. The multidrug-resistant strain group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa and A. baumannii and treated with nebulized colistin (5 million international units every 8 h) either in monotherapy (n=28) or combined to a 3-day intravenous aminoglycosides for 7-19 days. The primary endpoint was clinical cure rate. Aerosol was delivered using vibrating plate nebulizer., Results: After treatment, clinical cure rate was 66% in sensitive strain group and 67% in multidrug-resistant strain group (difference -1%, lower limit of 95% CI for difference -12.6%). Mortality was not different between groups (23 vs. 16%). Among 16 patients with persisting or recurrent P. aeruginosa infection, colistin minimum inhibitory concentration increased in two patients., Conclusion: Nebulization of high-dose colistin was effective to treat VAP caused by multidrug-resistant P. aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous β-lactams associated with aminoglycosides or quinolones for treating VAP caused by susceptible P. aeruginosa and A. baumannii.