title: Single, large, daily dosing versus intermittent dosing of tobramycin for treating experimental pseudomonas pneumonia.
abstract: Single, large, daily aminoglycoside doses in animals are less toxic than conventional dosing, and higher drug concentrations in vitro produce more-rapid bacterial killing. Thus, we compared various aminoglycoside dosing schedules in neutropenic (n = 153) and nonneutropenic (n = 192) guinea pigs with Pseudomonas aeruginosa pneumonia. Equivalent tobramycin dosages were given: 5 mg/kg every 4 h or 30 mg/kg every 24 h. Animals were serially killed during therapy, and quantitative lung cultures were performed. Bacterial titers in lungs dropped rapidly in all tobramycin-treated animals, both neutropenic and nonneutropenic, during the initial 16 h of therapy. In nonneutropenic guinea pigs, lung titers remained constant despite continued 4-h dosing. With subsequent 24-h dosing, titers continued to drop, and by 72 h there were a significant number of animals with sterile lungs (P less than .01). In neutropenic guinea pigs given tobramycin every 24 h, bacterial regrowth occurred; thus, therapy was ineffective. Adding mezlocillin, however, suppressed regrowth; thus, combination therapy was superior (P less than .05).
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0622.
authors.forename: J E
authors.initials: JE
authors.lastname: Kapusnik
authors.forename: C J
authors.initials: CJ
authors.lastname: Hackbarth
authors.forename: H F
authors.initials: HF
authors.lastname: Chambers
authors.forename: T
authors.initials: T
authors.lastname: Carpenter
authors.forename: M A
authors.initials: MA
authors.lastname: Sande
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D006168:Guinea Pigs; D008802:Mezlocillin / Q000008:administration & dosage / Q000627:therapeutic use; D009503:Neutropenia / Q000150:complications; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology; D014031:Tobramycin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D008802:Mezlocillin; D014031:Tobramycin