Exposure to radiation damages the immune, hematopoietic, and gastrointestinal components of the host defense system. This may lead to serious endogenous or exogenous infections. When radiation injury is combined with other physical trauma, e.g., burn or wound, the resulting damage to these systems is synergistic, and treatment for infection requires multiple approaches. This paper reviews successful single and combined therapeutic modalities for infections in irradiated mice and irradiated mice inflicted with trauma that are currently conducted at the Armed Forces Radiobiology Research Institute. The models of endogenous and exogenous infection and combined injury are described. The management of wounds infected with bacteria, exogenous systemic infection due to gram-negative enteric bacteria, and the chemoprophylaxis of enteric-derived systemic infection with quinolones is described. Infections can be treated successfully with proper antimicrobial therapy. In gamma- and neutron-irradiated mice, the immunomodulator trehalose dimycolate (TDM) was effective in treating endogenous infection. TDM with the antimicrobial ceftriaxone was effective in treating exogenous infection due to Klebsiella pneumoniae. Improvement in managing infection in irradiated and injured hosts will require further research using these diagnostic and therapeutic modalities. Accurate biological dosimetry is critical in determining if victims are at risk of developing infection. We found that radiation induced changes in plasma diamine oxidase activity; monitoring these changes was a useful indicator of the severity of radiation injury.
Ionizing radiation increases the recipient's susceptibility to local and systemic infection by endogenous and exogenous microorganisms. Most infections involve fatal Gram-negative septicemia, but those associated with trauma may be polymicrobial. The use of quinolone antimicrobial agents in the treatment of these infections in irradiated mice is reviewed. Quinolones were effective in controlling systemic endogenous Gram-negative infection following irradiation. Supplementation of quinolone therapy with penicillin prevented treatment failures due to Streptococci, and increased survival. Quinolones were found also to be effective in management of systemic exogenous infections due to orally ingested Klebsiella pneumoniae and Pseudomonas aeruginosa. A 21-day course of therapy of K. penumoniae infection was superior to a 7-day therapy. The effectiveness of quinolones in the management of these infections may be attributed to local inhibition of the offending organism's growth within the gut lumen, while preserving the anaerobic gut flora and their systemic antibacterial activity. Administration of agents effective against anaerobic bacteria may be required for the management of polymicrobial infections. Supplementing antianaerobic therapy with a quinolone can control the Gram-negative bacterial component of the infection and prevent Enterobacteriaceae translocation and mortality. The availability of an oral, as well as parenteral, route of administration, the advantage of achieving selective inhibition of potential pathogens in the gut, and the ability to treat systemic infection make the quinolones promising agents for the therapy of endogenous and exogenous infections after irradiation.
The effect of oral therapy with 6 quinolones, lomefloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, and CI-990 in the prevention of post-irradiation bacteraemia and mortality was tested in mice. Two models were used, the C3H/HeN mouse strain for endogenously acquired infection and the B6D2F1 mouse strain for studies of exogenously acquired Pseudomonas aeruginosa infection. Each therapy or water-fed control group included 40 mice, 20 for monitoring survival and 20 for obtaining liver cultures. In C3H/HeN mice, mortality in the groups that received each of the quinolones except CI-960 was significantly lower (P < 0.05) than in the water-treated mice. Survival was 54/60 (90%) with lomefloxacin 51/60 (85%) with ofloxacin, 50/60 (83%) with CI-990, 45/60 (75%) with sparfloxacin, 37/60 (62%) with temafloxacin, 9/60 (15%) for the control group, and 6/60 (10%) for CI-960. Enterobacteriaceae were isolated from 38 of 53 (72%) and Streptococcus spp. from 13 of 53 (25%) of the livers of control mice. The number of Enterobacteriaceae was lower in quinolone-treated mice. However, isolation of streptococci was similar to controls, except in those treated with sparfloxacin and CI-990. In B6D2F1 mice, mortality and isolation of P. aeruginosa in each of the quinolone group was significantly lower than for controls (P < 0.001). These data illustrate the efficacy of the quinolones in the therapy of exogenous infection, and the inability of those effective against anaerobic bacteria to prevent endogenous infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.