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Antimicrobial Agents and Chemotherapy, October 1999, p. 2389-2394, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model

Erika J. Ernst,1,* Satoru Hashimoto,2 Joseph Guglielmo,3 Teiji Sawa,4 Jean-Francois Pittet,4 Helmut Kropp,6 Jesse J. Jackson,6 and Jeanine P. Wiener-Kronish4,7

College of Pharmacy, University of Iowa, Iowa City, Iowa 522421; Department of Anesthesiology and Intensive Care Unit, Kyoto Prefectural University of Medicine, Kyoto, Japan 6022; Department of Clinical Pharmacy,3 Department of Anesthesia and Perioperative Care,4 and Department of Medicine and Cardiovascular Research Institute,7 University of California, San Francisco, California 94143; and Merck Research Laboratories, Rahway, New Jersey, 070656

Received 2 April 1999/Returned for modification 4 May 1999/Accepted 26 July 1999

The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in D-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

* Corresponding author. Mailing address: College of Pharmacy, S428 PHAR, University of Iowa, Iowa City, IA 52242-1112. Phone: (319) 335-8785. Fax: (319) 353-5646. E-mail: erika-ernst{at}uiowa.edu.

Antimicrobial Agents and Chemotherapy, October 1999, p. 2389-2394, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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