Single, large, daily dosing versus intermittent dosing of tobramycin for treating experimental pseudomonas pneumonia

J Infect Dis. 1988 Jul;158(1):7-12. doi: 10.1093/infdis/158.1.7.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Therapy, Combination
  • Guinea Pigs
  • Mezlocillin / administration & dosage
  • Mezlocillin / therapeutic use
  • Neutropenia / complications
  • Pneumonia / drug therapy*
  • Pneumonia / etiology
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / etiology
  • Tobramycin / administration & dosage*
  • Tobramycin / therapeutic use

Substances

  • Mezlocillin
  • Tobramycin