Nebulized ceftazidime in experimental pneumonia caused by partially resistant Pseudomonas aeruginosa

Ventilator-associated pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime is frequent in critically ill patients. The aim of the study was to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administrations of ceftazidime in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime. Ceftazidime was administered 24 h following the intra-bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration = 16 mu g ml(-1)), either by nebulization (25 mg kg(-1) every 3 h, n = 6) or by continuous intravenous infusion (90 mg kg(-1) over 24 h after an initial rapid infusion of 30 mg kg(-1), n = 6). Four non-treated inoculated animals served as controls. All piglets were killed 48 h (intravenous and control groups) or 51 h (aerosol group) after inoculation. Lung tissue concentrations and lung bacterial burden were assessed on multiple post-mortem sub-pleural lung specimens [(lower limit of quantitation = 10(2) colony forming unit (cfu g(-1))]. Ceftazidime trough lung tissue concentrations following nebulization were greater than steady-state lung tissue concentrations following continuous intravenous infusion [median and interquartile range, 24.8 (12.6-59.6) mu g g(-1) vs. 6.1 (4.6-10.8) mu g g(-1)] (p < 0.001). After 24 h of ceftazidime administration, 83% of pulmonary segments had bacterial counts < 10(2) cfu g(-1) following nebulization and only 30% following intravenous administration (p < 0.001). In control animals, 10% of lung segments had bacterial counts < 10(2) cfu g(-1) 48 h following bronchial inoculation. Nebulized ceftazidime provides more efficient bacterial killing in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime.