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.

Principles of Antimicrobial Use Prevent and Treat Infections in iradiated host

             Therapy for systemic infection due to Gram-negative bacteria in the immunocompromised host generally involves the use of a antimicrobials effective against aerobic and facultative Gram-negative bacilli  ( i.e. a fourth generation cephalosporin, an aminoglycoside, a quinolone ) and when needed also in combination with an agent active against aerobic gram positive cocci. ( i.e. a beta-lactam antibiotic, vancomycin). ( Pascoe & Steven. Antibiotics for the prevention of febrile neutropenia. Curr Opin Hematol. 2009 ;.)
             An additional approach in the prevention of such infection is the selective decontamination of the gastrointestinal tract by using agents that spare the anaerobic gut flora while inhibiting Enterobacteriaceae. Selective decontamination utilizes antimicrobial that are active against potential pathogens while sparing the normal flora that is able to interfere with the acquisition of virulent bacteria. (See figure below)

Role of  normal flora in interfering with the ability of pathogens to colonize and invade



              Several quinolone compounds exhibit high in vitro bactericidal activity against most Gram-negative bacteria. ( 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).
               These agents also can be administered orally and are relatively free of serious side effects. Quinolones also are effective in the management of septic episodes in neutropenic patients. Furthermore, selective decontamination of the gut with orally administered quinolones is used to prevent sepsis in immunocompromised hosts. ( Herbst et al.  Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy. Cochrane Database Syst Rev. 2009;CD007107; Brook & Elliott. Quinolone therapy in the prevention of mortality after irradiation. Radiat Res, 128, 100, 1991.)
                Selective decontamination of the bowel using antimicrobial agents, which are effective against only the aerobic and facultative anaerobic flora, is aimed at eliminating these bacteria while preserving the anaerobic bowel flora. The use of quinolone antimicrobial agents in the treatment of these infections in irradiated mice is effective in controlling systemic endogenous Gram-negative infection following irradiation. ( Brook & Ledney. Ofloxacin and penicillin-G in the prevention of bacterial translocation and animal mortality after irradiation. Antimicrob Agents Chemother, 35, 1685, 1991.)(See figure below)


Administration of ofloxacin inhibits Enterobacteriacae and spares the anaerobic gastrointestinal flora. (Brook & Ledney, 1991)


                   
                     Supplementation of quinolone therapy with penicillin prevents treatment failures due to streptococci and increases survival after non-lethal doses of 60Co-gamma irradiation. (Brook et al. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: comparison of pefloxacin, ciprofloxacin, and ofloxacin. Radiat Res, 122, 215, 1990.; Brook & Ledney: Ofloxacin and Penicillin-G in the Prevention of Bacterial Translocation and Animal Mortality after Irradiation.  Antimicrobial Agent and Chemotherapy. 35:1685; 1991; Brook & Ledney, 1992 )(See figure below)

Brook & Ledney, 1991 
                  Quinolones also are effective in managing systemic exogenous infections due to orally ingested K. pneumoniae and P. aeruginosa. ( Brook & Ledney. Oral ofloxacin therapy of Pseudomonas aeruginosa sepsis in mice after irradiation. Antimicrob Agents Chemother, 34, 1387, 1990; Brook & Ledney. Short and long courses of ofloxacin therapy of Klebsiella pneumoniae sepsis following irradiation. Radiat Res, 130, 61, 1992.).  A 21-day course of therapy for K. pneumoniae infection is superior to a 7-day course of therapy. ( Brook & Ledney . Oral aminoglycoside and ofloxacin therapy in the prevention of gram-negative sepsis after irradiation. J Inf Dis, 164, 917, 1991; Brook & Ledney, 1992 )(See figure below)

Brook & Ledney, 1992

                 The effectiveness of quinolones in the management of these infections may be attributed to local inhibition of the exogenous organism’s growth within the gut lumen while preserving the anaerobic gut flora and their systemic antibacterial activity. (Brook & Ledney.  The treatment of irradiated mice with polymicrobial infection caused by Bacteroides fragilis and Escherichia coli. J Antimicrob Chemother, 33, 243, 1994.)                

                 To investigate whether oral gentamicin therapy protects against gram-negative sepsis after irradiation, mice were exposed to 7.5 Gy of radiation from 60Co, infected with 107 Pseudomonas aeruginosa orally 3 days after irradiation, and treated with oral or intramuscular (im) gentamicin or oral ofloxacin. (Brook & Ledney: Oral Aminoglycoside and Ofloxacin Therapy in the Prevention of Gram-Negative Sepsis after Irradiation.  Journal of Infectious Diseases. 164: 917;1991; Brook & Ledney, 1992 ) Gentamicin therapy was started orally after 10 and 24 hours and im 24 h after inoculation. Mice that received oral gentamicin early (after 10 hours ), im gentamicin, showed significantly (P < .05) reduced colonization, translocation, and mortality compared with mice that received oral gentamicin late. (see figure below) These data support the use of selective antimicrobial therapy to reduce colonization, translocation, and mortality from gram-negative bacteria in irradiated animals.


Brook & Ledney, 1991
                   Administration of antimicrobial agents effective against anaerobic bacteria may be required for the management of aerobic-anaerobic polymicrobial infections. Supplementing anti-anaerobic therapy with a quinolone can control the Gram-negative bacterial component of the infection and prevent Enterobacteriaceae translocation and mortality ( Viscoli C. Antibacterial prophylaxis in neutropenic patients. Int J Antimicrob Agents. 2007 Nov;30 Suppl 1:S60-5).
                   The availability of an oral and a 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 following irradiation. 



                     However, growing antimicrobial resistance by potential pathogens against these and other antimicrobial agents warrants careful and controlled use.  ( Brook & Ledney. Quinolone therapy in the prevention of endogenous and  exogenous infection after irradiation. J Antimicrob Chemother; 33:777,1994; Brook & Ledney, 1992 )
                    Trimethoprim-sulfamethoxazole also was used for selective decontamination in immunocompromised individuals. Hammond & Baden . Antibiotic prophylaxis during chemotherapy-induced neutropenia for patients with acute leukemia. Curr Hematol Malig Rep. 2007; ;2: 97).  However, this agent has been known to cause idiopathic marrow suppression and may be detrimental in irradiation injury.
                    Topical antimicrobial treatment of wounds and burns can increase survival of victims of combined injury (radiation plus burn or wound). Madonna et al.: Treatment of Mice with Sepsis with Antibiotics and Synthetic Trehalose Dicorynomycolate (S-TDCM) Following Irradiation and Trauma in Mice.  J. Trauma 1991; 31:316.)

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