Purpose: Well characterized animal models that mimic the human response to potentially lethal doses of radiation are necessary in order to assess the efficacy of candidate medical countermeasures under the criteria of the U.S. Food and Drug Administration “Animal Rule”. Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity under scenarios likely to be present in the human population during mass casualty situations. These scenarios include understanding the impact of medical management on survival of the hematopoietic acute radiation syndrome (H-ARS). Little information is available to compare the impact of medical management under identical study conditions. The work presented here provides a comparison of the impact of different levels of medical management (supportive care) on the survival outcome in two large animal models: the male Gottingen minipig and the male rhesus macaque (NHP). Materials and Methods: In the context of this comparison, limited supportive care consisted of administration of analgesics only, standard supportive care consisted of prophylactic administration of analgesics, antibiotics and fluids (minipigs) or analgesics, antibiotics, antidiarrheals, nutritional and fluid support (NHP) on a set schedule regardless of indication, and full supportive care (NHP only) consisted of analgesics, antibiotics, antidiarrheals, nutritional and fluid support, antiemetics and blood transfusions on an individual animal, trigger-to-treat regimen. Regardless of level of supportive care, minipigs were exposed to total body irradiation using a Co⁶⁰ source and NHPs were exposed to total body irradiation using 6 MV photon energy. Results: Based on estimated LD50 values, the inclusion of antimicrobial or broad-spectrum antibiotics provided a dose modifying factor (DMF) of 1.09 in the minipig, and by 1.15 in the NHP (standard supportive care to limited supportive care ratio. For the NHP, the administration of supportive care based on symptomology rather than a set schedule, and inclusion of blood transfusions yielded a DMF of 1.05 (full supportive care to standard supportive care ratio). Conversely, comparison of the estimated LD50 values between full supportive care and limited supportive care in the NHP provided a DMF of 1.21. Conclusion: The study reported here provides a comparison of the impact of antibiotic administration on radiation-induced lethality.

目的为了根据美国食品药品管理局“动物法则”的标准评估候选医学对策的功效，必须模拟动物对人类潜在的致命剂量反应的良好特征的动物模型。模型的开发需要确定在大规模伤亡情况下人群中可能出现的情景下的辐射剂量反应关系以及死亡率和发病率的时程。这些场景包括了解医疗管理对造血急性放射综合症（H-ARS）生存的影响。在相同的研究条件下，几乎没有信息可用来比较医疗管理的影响。材料和方法：在这种比较的背景下，有限的支持治疗仅包括镇痛药的使用，标准的支持治疗包括预防性使用镇痛药，抗生素和液体（minipigs）或止痛药，抗生素，止泻药，营养和液体支持（NHP） ），无论是否有适应症，都应按既定时间表进行，全面支持治疗（仅适用于NHP）包括止痛药，抗生素，止泻药，营养和体液支持，止吐药和对个体动物的输血，即刻治疗。无论支持治疗的水平如何，小型猪都使用Co ⁶⁰光源进行全身照射，而NHP则使用6 MV光子能量进行全身照射。结果：根据估计的LD50值，在小型猪中加入抗微生物或广谱抗生素可提供1.09的剂量调节因子（DMF），在NHP中提供1.15的剂量调节因子（标准支持治疗至有限的支持治疗比率。对于NHP，根据症状而不是按照既定时间表进行支持治疗，包括输血，DMF为1.05（完全支持治疗与标准支持治疗比率）。相反，比较完全支持治疗和有限支持治疗之间的LD50估计值NHP的护理提供了1.21的DMF。结论：此处报道的研究提供了抗生素给药对放射线致死率影响的比较。