Lung Deposition and Efficiency of Nebulized Amikacin duringEscherichia coliPneumonia in Ventilated Piglets

Abstract

Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg x kg-1, n = 10) or by intravenous infusion (15 mg x kg-1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 +/- 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 +/- 175 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x g-1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units. g-1 versus median = 5 x 10(2) colony forming units x g-1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.

Feasibility of aerosolized colistin in the era of escalating drug-resistant Pseudomonas pneumonia: pressing need for validation clinical trials

“…In this study, Lu et al demonstrated that, in areas of severe pneumonia, lower drug concentration occurred with inhaled colistin compared with areas with mild pneumonia; these observations echoed results of prior studies using aminoglycosides [12]. However, despite lung tissue concentrations influenced by severity of lung lesions, inhaled colistin was associated with comparable bacterial clearance in lung segments with mild and severe Intensive Care Med (2010) 36:1110-1111 DOI 10.1007/s00134-010-1883-8 EDITORIAL Pseudomonas pneumonia [11].…”

Effects of glucocorticoids in ventilated piglets with severe pneumonia

“…This model closely resembles human pneumonia and has proven to be very useful for evaluating different aspects related to the diagnosis and treatment of severe pneumonia [21][22][23][24][25][26][27]. Using this animal model, severe pneumonia was reproduced and the associated inflammatory response was studied after inoculation with high concentrations of Pseudomonas aeruginosa [28], the most lethal causative microorganism, both in CAP and ventilator-associated pneumonia [2,8,29].…”

Experimental Pseudomonas aeruginosa pneumonia: evaluation of the associated inflammatory response

“…MARQUETTE et al [7] have developed an animal model of pneumonia in mechanically ventilated piglets that closely resembles severe human pneumonia. This model has proved to be very useful for the proper evaluation of different aspects regarding diagnosis and treatment [8][9][10][11][12][13]. Pseudomonas aeruginosa is one of the most lethal causative microorganisms both in communityacquired pneumonia and ventilator-acquired pneumonia [1,2,6].…”