Oral Aminoglycoside and Ofloxacin Therapy in the Prevention of Gram-Negative Sepsis after Irradiation

Abstract

To investigate whether oral gentamicin or ofloxacin therapy protects against gram-negative sepsis after irradiation, B6D2F1 mice were exposed to 7.5 Gy of radiation from 60Co, infected with 10(7) Pseudomonas aeruginosa or Klebsiella pneumoniae orally 3 days after irradiation, and treated with oral (15 mg/kg/day) or intramuscular (im; 7.5 mg/kg/day) gentamicin or oral (40 mg/kg/day) ofloxacin. For P. aeruginosa, gentamicin therapy was started orally 10 and 24 h and im 24 h after inoculation. For K. pneumoniae, gentamicin was started orally 24, 48, and 72 h and im 24 h after inoculation; ofloxacin was started 24 h after inoculation. Mice that received oral gentamicin early (10 h for P. aeruginosa, 24 h for K. pneumoniae), im gentamicin, or oral ofloxacin showed significantly (P less than .05) reduced colonization, translocation, and mortality compared with mice that received oral gentamicin late. These data support the use of selective antimicrobial therapy to reduce colonization, translocation, and mortality from gram-negative bacteria in irradiated animals.