title: Effects of antibiotic therapy on Pseudomonas aeruginosa-induced lung injury in a rat model.
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 10(7) 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.
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA. erika-ernst@uiowa.edu
authors.forename: E J
authors.initials: EJ
authors.lastname: Ernst
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: J
authors.initials: J
authors.lastname: Guglielmo
authors.forename: T
authors.initials: T
authors.lastname: Sawa
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: H
authors.initials: H
authors.lastname: Kropp
authors.forename: J J
authors.initials: JJ
authors.lastname: Jackson
authors.forename: J P
authors.initials: JP
authors.lastname: Wiener-Kronish
mesh_terms: D000818:Animals; D001398:Aztreonam / Q000494:pharmacology / Q000627:therapeutic use; D015377:Cilastatin / Q000494:pharmacology / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004195:Disease Models, Animal; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use*; D015378:Imipenem / Q000494:pharmacology / Q000627:therapeutic use; D008171:Lung Diseases / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000494:pharmacology / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004338:Drug Combinations; D008997:Monobactams; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D001398:Aztreonam