The accidental or hostile exposure of individuals to ionizing irradiation is of great public and military concern. Radiation sickness (acute radiation syndrome, or ARS) occurs when the body is exposed to a high dose of penetrating radiation within a short period of time. Systemic infection is one of the serious consequences of ARS. There is a direct relation between the magnitude of radiation exposure and the risk of developing infection. The risk of systemic infection is higher whenever there is a combined injury such as burn or trauma. Ionizing radiation enhances infection by allowing translocation of oral and gastrointestinal flora, and reducing the threshold of sepsis due to endogenous and exogenous microorganisms. The potential for concomitant accidental or terrorism-related exposure to bio-terrorism agents such as anthrax and radiation also exists.

This site is made of a home page that presents new developments and updates on the management of acute radiation syndrome including concomitant exposure to radiation and anthrax. Separate pages are dedicated to the treatment modalities.

Research of Post-Irradiation Sepsis


                  The mainstay of treatment of irradiation victims is the prevention and management of infection. Because, no controlled studies of therapeutic intervention in humans are available most of the current recommendations are based on animal research. Unfortunately, the clinical experience in treating infections in patients that develop neutopenia and immunosupression as a result of chemotherapy or total body irradiation can not be used to provide guidance for therapy for infection after exposure to ionizing radiation. This is because the infection and other pathology that develop following exposure to ionizing radiation is unique. ( Kaplan et al. Impairment of antimicrobial defenses following total body irradiation of mice. J Lab Clin Med, 40, 682, 1958; Brook et al. Effect of radiation dose on the recovery of aerobic and anaerobic bacteria from mice. Can J Microbiol, 32, 719, 1986.)

Table: Differences in the management of infection following irradiation and febrile neutropenia

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•Irradiation damages the whole body (hematopoetic, GIT, lung , CNS).
•Combined injuries may exist (wounds , burns).
•The response of irradiated host to antimicrobials is sometimes unpredictable.
•Suppression of the anaerobic flora has untoward effects.
•In case of mass casualty, antimicrobial resistance can emerge and use of oral agents may be the only option.


The recommended treatment is therefore based on research that was done in animal models that established the pathogenesis and the principles for the prevention and treatment of post-irradiation sepsis. This research provides basic guidance concerning the selection of proper antimicrobials for therapy of sepsis in humans. 



               The origin of most post-irradiation infections is the gastrointestinal tract, which generally is colonized by aerobic and anaerobic bacteria. After irradiation of mice with an LD50 , a decrease from 1010-12 to 104-6 bacteria per gram stool occurs in the number of aerobic and facultative anaerobic bacteria in the ileum of mice. That decrease begins 2 days after irradiation and is maximal 9 days after 60Co-gamma photon irradiation. ( Brook et al, Effect of antimicrobial therapy on the gut flora bacterial infection in irradiated mice. Int J Radiat Biol, 53, 709, 1988.) However, after day 9, the number of Enterobacteriaceae increases and returns to the previous number within 3–5 days, but the number of anaerobes stays low. The increase in the Enterobacteriaceae numbers coincides with the appearance of endogenous Escherichia coli and Proteus mirabilis in the blood, spleen, and liver of the animals and the emergence of mortality.  ( Brook I, et al. Recovery of aerobic and anaerobic bacteria from irradiated mice. Infect Immun, 46, 270, 1984 :  Brook & Laedney, 1992).

Brook et al, 1988



Another potential source of serious infection in the irradiated host is an exogenous organism, such as Pseudomonas aeruginosa or Klebsiella pneumoniae. Animals exposed to 60Co-gamma radiation become susceptible to colonization and systemic infections with these organisms, starting 2 days after irradiation.


Pseudomonas aeuginosa
Klebsiella pneumoniae

Mortality in mice exposed to 10 Gy 60Co-gamma irradiation and treated with metronidazole, alone or in combination with gentamicin, occurs earlier than in the controls (P < 0.001). (Brook et al. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice. Int J Radiat Biol Stud Phys Chem Med, 53:709, 1988; Brook & Ledney, 1992 )  Microorganisms are recovered from the blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. The predominant organisms recovered from these animals were Enterobacteriaceae.

Brook et al, 1988

As compared to untreated mice, a rapid decrease (by 8.8 logs) in the number of anaerobic flora occurred in the mice treated with metronidazole 5 days after irradiation. This change preceded a rapid increase in the number of aerobic organisms, which coincides with the earlier mortality in this group. These data suggest that antimicrobial agents that decrease the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, and contribute to the mortality after irradiation.

           







           Polymicrobial intra-abdominal infection involving such aerobic and anaerobic bacteria as E. coli and Bacteroides fragilis can occur following irradiation associated with intra-abdominal trauma. Previous studies have illustrated the importance of administering antimicrobials that are effective against both of these organisms for the successful management of such infections. ( Solomkin et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.  Clin Infect Dis. 2010 ;50:133). 

           However, treatment of mixed aerobic-anaerobic infections in irradiated hosts may be complicated by the adverse effects following the use of antimicrobials that are capable of reducing the number of the anaerobic gut flora. (Brook et al. Effect of antimicrobial therapy on the gut flora bacterial infection in irradiated mice. Int J Radiat Biol, 53, 709, 1988 ; Brook & Ledney, 1992 ).

Therapy for mixed aerobic and anaerobic infections reduces the number of anaerobic gut flora, allows overgrowth of the aerobic flora and results in increased mortality due to sepsis with Enterobacteriaceae.

Nuclear War. Painted by Itzhak Brook in 1957


             
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