title: Aerosolization of imipenem/cilastatin prevents pseudomonas-induced acute lung injury.
abstract: Aerosolization of imipenem/cilastatin was compared with continuous intravenous infusions of the antibiotic for pharmacokinetic/pharmacodynamic analysis. The concentrations of imipenim/cilastatin in bronchoalveolar lavage fluids (BAL) obtained from rats exposed to the aerosolized antibiotic were significantly greater than the concentrations in BAL in the rats that had received intravenous infusions of imipenem/cilastatin. The two methods of antibiotic delivery were compared for their effects on bacterial-induced lung injury in rats that had Pseudomonas aeruginosa instilled into their airspaces. The aerosolization of antibiotic was associated with significantly decreased bacterial-induced lung injury. The high concentrations of antibiotic in the airspaces secondary to aerosolization appears to kill bacteria more quickly and preserve lung epithelial and endothelial integrity better than systemic delivery of the same antibiotic.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: E
authors.initials: E
authors.lastname: Wolfe
authors.forename: B
authors.initials: B
authors.lastname: Guglielmo
authors.forename: R
authors.initials: R
authors.lastname: Shanks
authors.forename: J
authors.initials: J
authors.lastname: Sundelof
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: E
authors.initials: E
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Wiener-Kronish
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D015377:Cilastatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000382:microbiology*; D008297:Male; D010539:Permeability / Q000187:drug effects; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000336:Aerosols; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination