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Quinolone therapy in the management of infection after irradiation
1Experimental Hematology Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20899-5145.
Abstract:
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.
Insights
Quinolone antimicrobials effectively treat Gram-negative septicemia and polymicrobial infections in irradiated mice. Combining quinolones with penicillin or antianaerobic agents improves survival against Streptococci and prevents mortality.
Area of Science:
- Microbiology
- Infectious Diseases
- Radiation Biology
Background:
- Ionizing radiation compromises the immune system, increasing susceptibility to infections.
- Infections post-irradiation often involve Gram-negative bacteria, including septicemia, and can be polymicrobial, especially with trauma.
- Endogenous and exogenous microorganisms pose significant threats in immunocompromised individuals.
Purpose of the Study:
- To review the efficacy of quinolone antimicrobial agents in treating infections in irradiated mice.
- To evaluate quinolones for controlling Gram-negative septicemia and polymicrobial infections.
- To assess the role of quinolones in conjunction with other antimicrobials.
Main Methods:
- Review of studies utilizing quinolone antimicrobial agents in irradiated mouse models.
- Analysis of treatment outcomes for systemic endogenous and exogenous infections.
- Evaluation of combination therapies including penicillin and antianaerobic agents.
Main Results:
- Quinolones demonstrated effectiveness in controlling systemic endogenous Gram-negative infections post-irradiation.
- Supplementation with penicillin improved survival by preventing Streptococcal treatment failures.
- Quinolones were effective against exogenous Klebsiella pneumoniae and Pseudomonas aeruginosa, with longer therapy durations showing superiority.
Conclusions:
- Quinolones are promising for managing infections after irradiation due to gut flora preservation and systemic activity.
- Combination therapy, including antianaerobic agents, may be necessary for polymicrobial infections.
- Quinolones offer advantages in oral/parenteral administration and selective pathogen inhibition for post-irradiation infections.