The management of established or suspected infection following exposure to radiation is characterized by neutropenia and fever) is similar to that used for other febrile neutropenic patients. ( Reeves GI. Medical implications of enhanced radiation weapons. Mil Med. 2010 ;175: 964 )However, important differences between the two conditions exist. Individuals exposed to irradiation are otherwise healthy, they have no protection of selected parts of their body such as the gastrointestinal tract, and the response of irradiated animals to antimicrobial therapy is sometimes unpredictable, as was evident in some of our work where metronidazole ( 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). and pefloxacin ( Patchen et al. Adverse effects of pefloxacin in irradiated C3H/HeN mice: correction with glucan therapy. Antimicrob Agents Chemother; 37:1882,1993) therapies were detrimental.
Antimicrobial agents that decrease the number of the strict anaerobic component of the gut flora (i.e., metronidazole) generally should not be given because they may enhance systemic infection by aerobic or facultative anaerobic bacteria, thus facilitating mortality after irradiation. The patient that develops neutropenia after radiation is susceptible to irradiation damage to other tissues, such as the lungs and the central nervous system. These patients may require therapeutic interventions not needed in other types of neutropenic patients.
An empirical regimen of antibiotics should be selected, based on the pattern of bacterial susceptibility and nosocomial infections in the particular area and institution and the degree of neutropenia. Broad-spectrum empirical therapy (see below for choices) with high doses of one or more antibiotics should be initiated at the onset of fever.
These antimicrobials should be directed at the eradication of Gram-negative aerobic organisms that account for more than three-fourths of the isolates causing sepsis. (Brook et al. Management of postirradiation infection: lessons learned from animal models. Mil Med. 2004;169:194) Because aerobic and facultative Gram-positive bacteria (mostly alpha-hemolytic streptococci) cause sepsis in about a quarter of the victims, coverage for these organisms may be necessary in the rest of the individuals.
Streptococcus spp.
A standardized plan for the management of febrile, neutropenic patients must be devised in each institution or agency. Empirical regimens must contain antibiotics broadly active against aerobic and facultative Gram-negative bacteria ( Klebsiella pneumoniae, Pseudomonas aeruginosa ). These include: a quinolones [i.e. ciprofloxacin, levofloxacin], a fourth-generation cephalosporins [e.g. cefepime ceftazidime ],or an aminoglycoside [i.e. gentamicin, amikacin]). Antibiotics directed against Gram-positive bacteria need to be included in instances and institutions where infections due to these organisms are prevalent. These include: amoxicillin, vancomycin, or lenizolid.
Table: Antimicrobial Therapy for Sepsis after Irradiation (Duration 21-28 days)
Quinolones, 2nd or 3rd generation
Ciprofloxacin (2nd) or Levofloxacin (3rd)
Cephalosporins, 3rd or 4th generation
Ceftriaxone (3rd) or Cefepime (4th)
Aminoglycosides
Gentamicin or Amikacin
± Amoxicillin or Vancomycin
± Amphotericin B (persistent fever 7 days on Rx)
These are the antimicrobial agents suggested for therapy of infection following exposure to irradiation:
a. First choice: ciprofloxacin (a second-generation quinolone) or levofloxacin (a third-generation quinolone) +/- amoxicillin or vancomycin.
Ciprofloxacin is effective against Gram-negative organisms (including Pseudomonas species) but has poor coverage for Gram-positive organisms (including Staphylococcus aureus and Streptococcus pneumoniae) and some atypical pathogens. Levofloxacin has expanded Gram-positive coverage (penicillin-sensitive and penicillin-resistant S. pneumoniae) and expanded activity against atypical pathogens.
b. Second choice: ceftriaxone (a third-generation cephalosporin) or cefepime (a fourth-generation cephalosporin) +/- amoxicillin or vancomycin.
Cefepime exhibits an extended spectrum of activity for Gram-positive bacteria (staphylococci) and Gram-negative organisms, including Pseudomonas aeruginosa and certain Enterobacteriaceae that generally are resistant to most third-generation cephalosporins. Cefepime is an injectable and is not available in an oral form.
c. Third choice: gentamicin or amikacin (both aminoglycosides) +/- amoxicillin or vancomycin (all injectable).
Aminoglycosides should be avoided whenever feasible due to associated toxicities.
The second and third choices of antimicrobials are suitable for children because quinolones are not approved for use in this age group.
The use of these agents should be considered in individuals exposed to doses above 1.5 Gy, should be given to those who develop fever and neutropenia and should be administered within 48 hours of exposure. An estimation of the exposure dose should be done by biological dosimetry whenever possible and by detailed history of exposure.
If infection is documented by cultures, the empirical regimen may require adjustment to provide appropriate coverage for the specific isolate(s). When the patient remains afebrile, the initial regimen should be continued for a minimum of 7 days. Therapy may need to be continued for at least 21–28 days or until the risk of infection has declined because of recovery of the immune system. A mass casualty situation may mandate the use of oral antimicrobials.
Modifications of this initial antibiotic regimen should be made when microbiological culture shows specific bacteria that are resistant to the initial antimicrobials. The modification, if needed, should be influenced by a thorough evaluation of the history, physical examination findings, laboratory data, chest radiograph, and epidemiological information. Antifungal coverage with amphotericin B may need to be added, if indicated, for those who remain persistently febrile for 7 days or more on antimicrobial therapy in association with clinical evidence of infection or if they have new fever on or after day 7 of antimicrobial therapy. If resistant Gram-positive infection is evident, vancomycin should be added. If diarrhea is present, cultures of stool should be examined for enteropathogens (i.e., Salmonella, Shigella, Campylobacter, and Yersinia). Oral and pharyngeal mucositis and esophagitis suggest Herpes simplex infection or candidiasis. Either empirical antiviral or antifungal therapy or both should be considered.
