Effects of antibiotic therapy on Pseudomonas aeruginosa lung injury in a rat model

The effect of antibiotics on the acute lung injury induced by virulent Pseu domonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung i njury was induced by the instillation of PA103 directly into the right lowe r lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as sep arate, independent parameters of acute lung injury, Four hours after the in stillation of PA103, all the parameters were increased linearly depending o n the dose of P. aeruginosa, Nest, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in D-galac tosamine-sensitized rats. One hour after the rats received 10(7) CFU of PA1 03, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cila statin (30 mg/kg) was administered. Despite an MIC indicating resistance, i mipenem-cilastatin improved all the measurements of lung injury; in contras t, aztreonam? which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different q uantities of plasma endotoxin; therefore, endotoxin did not appear to expla in the differences in lung injury. This in vivo model is useful to quantita tively compare the efficacies of parenteral antibiotic administration on Ps eudomonas airspace infections.