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

Erika J Ernst; Satoru Hashimoto; Joseph Guglielmo; Teiji Sawa; Jean-Francois Pittet; Helmut Kropp; Jesse J Jackson; Jeanine P Wiener-Kronish

doi:10.1128/AAC.43.10.2389

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

Journal article

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Peer reviewed

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

Erika J Ernst, Satoru Hashimoto, Joseph Guglielmo, Teiji Sawa, Jean-Francois Pittet, Helmut Kropp, Jesse J Jackson and Jeanine P Wiener-Kronish

Antimicrobial agents and chemotherapy, Vol.43(10), pp.2389-2394

10/01/1999

DOI: 10.1128/AAC.43.10.2389

PMCID: PMC89488

PMID: 10508012

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Abstract

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.

Drug Therapy, Combination

Experimental Therapeutics

Lung Diseases

Pseudomonas aeruginosa

Pseudomonas Infections

Details

Title: Subtitle: Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model
Creators: Erika J Ernst - University of Iowa
Satoru Hashimoto - Kyoto Prefectural University of Medicine
Joseph Guglielmo - University of California, San Francisco
Teiji Sawa - University of California, San Francisco
Jean-Francois Pittet - University of California, San Francisco
Helmut Kropp - Merck & Co., Inc., Rahway, NJ, USA (United States)
Jesse J Jackson - Merck & Co., Inc., Rahway, NJ, USA (United States)
Jeanine P Wiener-Kronish - University of California, San Francisco
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.43(10), pp.2389-2394
DOI: 10.1128/AAC.43.10.2389
PMID: 10508012
PMCID: PMC89488
NLM abbreviation: Antimicrob Agents Chemother
ISSN: 0066-4804
eISSN: 1098-6596
Publisher: American Society for Microbiology
Language: English
Date published: 10/01/1999
Academic Unit: Pharmacy Practice and Science
Record Identifier: 9984366037102771

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