Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa

Emergence of multidrug-resistant strains in intensive care units has renewed interest in colistin, which often remains the only available antimicrobial agent active against resistant Pseudomonas aeruginosa. The aim of this study is to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administration of colistin in piglets with pneumonia caused by P. aeruginosa. In ventilated piglets, colistimethate was administered 24 h following bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration of colistin = 2 mu g ml(-1)) either by nebulization (8 mg kg(-1) every 12 h, n = 6) or by intravenous infusion (3.2 mg kg(-1) every 8 h, n = 6). All piglets were killed 49 h after inoculation. Colistin peak lung tissue concentrations and lung bacterial burden were assessed on multiple post mortem subpleural lung specimens. Median colistin peak lung concentration following nebulization was 2.8 mu g g(-1) (25-75% interquartile range = 0.8-13.7 mu g g(-1)). Colistin was undetected in lung tissue following intravenous infusion. In the aerosol group, peak lung tissue concentrations were significantly greater in lung segments with mild pneumonia (median = 10.0 mu g g(-1), 25-75% interquartile range = 1.8-16.1 mu g g(-1)) than in lung segments with severe pneumonia (median = 1.2 mu g g(-1), 25-75% interquartile range = 0.5-3.3 mu g g(-1)) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts < 10(2) cfu g(-1) following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts < 10(2) cfu g(-1) 49 h following bronchial inoculation. Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.