Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.
Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.
Jahraus
Christopher D
CD
Assurance Oncology Services, 70 Bowden Circle, Chelsea, AL 35043-3215, USA. chris@assuranceonc.com
Schemera
Bettina
B
Rynders
Patricia
P
Ramos
Melissa
M
Powell
Charles
C
Faircloth
John
J
Brawner
William R
WR
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007958:Leukocyte Count; D009355:Neomycin / Q000627:therapeutic use; D009503:Neutropenia / Q000188:drug therapy* / Q000209:etiology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D000890:Anti-Infective Agents; D012294:Rifamycins; D009355:Neomycin; D000078262:Rifaximin