Management of postirradiation infection: lessons learned from animal models.

Abstract

Ionizing radiation depresses host defenses and enhances susceptibility to local and systemic infection due to endogenous or exogenous microorganisms. Exposure of mice to a lethal dose of ionizing 60Co-gamma radiation induces a dose-related reduction in the number of both aerobic and anaerobic bacteria from 10(10-12) to 10(4-6) per gram of stool within 4 days. The number of anaerobic bacteria stays low, but the number of Enterobacteriaceae per gram of stool increases significantly up to 10(9) by the 12th day after irradiation. This increase is associated with bacterial translocation of these organisms and fatal bacteremia. The use of quinolones in the irradiated animals was effective in controlling systemic endogenous Gram-negative infection after irradiation. Supplementation with penicillin prevented treatment failures due to Streptococcus spp. and increased survival. Quinolones given for 21 days also were effective in management of systemic exogenous infections due to orally ingested Klebsiella pneumoniae and Pseudomonas aeruginosa. Effectiveness of quinolones may be attributed to inhibition of exogenous organism growth within the gut lumen while preserving the anaerobic gut flora as well as their systemic antibacterial activity. Based on these findings, antimicrobial agents recommended for therapy of infection after exposure to irradiation are: ciprofloxacin, levofloxacin, ceftriaxone, cefepime, gentamicin +/- amoxicillin, or vancomycin.