Quinolone and Glycopeptide Therapy for Infection in Mouse Following Exposure to Mixed-field Neutron-γ-photon Radiation

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Abstract
The effects of increased doses of mixed-field neutron-gamma-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. Animals were given 4.25, 4.50, 4.75, 5.00 and 5.25 Gy of mixed-field [n/(n+gamma) = 0.7] radiation. The mortality rate of mice and recovery of bacteria were directly related to the radiation dose. Enterobacteriaceae were mostly isolated from the livers of mice exposed to 5.00 and 5.25 Gy, and aerobic Gram-positive cocci were recovered from those exposed to 4.50 and 4.75 Gy. Oral therapy with L-ofloxacin reduced mortality of all groups of animals except those given 4.25 and 4.50 Gy. This reduction was associated with a decrease in the number of the recovered Enterobacteriaceae. However, the number of Gram-positive cocci was unaffected. Addition of i.m. glycopeptide therapy failed to prevent Gram-positive coccal infection, due to the development of glycopeptide-resistant Enterococcus faecalis. These data demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host.