title: Aerosolized recombinant human lysozyme enhances the bactericidal effect of tobramycin in a hamster model of Pseudomonas aeruginosa-induced pneumonia.
abstract: Previous studies from this laboratory have shown that aerosolized recombinant human lysozyme (rhLZ) mitigates Pseudomonas aeruginosa (PA)-induced pneumonia. In the current investigation, our laboratory tested the hypothesis that aerosolized rhLZ can potentiate the effects of tobramycin (TBMN), thereby reducing the effective dose of this agent in the treatment of PA-induced pneumonia. Syrian hamsters were instilled intratracheally with PA, then exposed to an aerosol containing either 1% rhLZ, 3 μg TBMN, or a combination of both agents. In contrast to the initial studies with rhLZ, which involved 3 separate aerosol exposures, only a single treatment was used in the current investigation. Twenty-four hours after completion of the aerosol regimen, the following parameters were measured: (1) whole-lung colony-forming units (CFU), (2) total bronchoalveolar lavage fluid (BALF) CFU, (3) lung histopathology, and (4) total BALF neutrophils. The combination of rhLZ and TBMN significantly reduced whole-lung and BALF CFU, as well as the inflammatory index, compared to TBMN alone. Similar results were seen in vitro with regard to bactericidal activity. These findings provide a rationale for clinical testing of rhLZ as an adjunct to commercial antibiotic treatment.
authors.affiliation: Department of Pharmacy and Allied Health Sciences, St John's University, New York, New York, USA.
authors.forename: Tapan
authors.initials: T
authors.lastname: Bhavsar
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Xingjian
authors.initials: X
authors.lastname: Liu
authors.forename: Jerome
authors.initials: J
authors.lastname: Cantor
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006224:Cricetinae; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008647:Mesocricetus; D009113:Muramidase / Q000627:therapeutic use*; D009504:Neutrophils / Q000166:cytology; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa; D011994:Recombinant Proteins / Q000627:therapeutic use; D014031:Tobramycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D009113:Muramidase; D014031:Tobramycin