Craig W A, Turner J H, Kunin C M
Infect Immun. 1974 Aug;10(2):287-92. doi: 10.1128/iai.10.2.287-292.1974.
Pretreatment with multiple doses of polymyxin B and colistimethate was evaluated as to its ability to sequester sufficient antibiotic in tissues to neutralize the effects of endotoxin in three animal models. Animals were challenged with endotoxin 24, 48, or 72 h after the last dose of antibiotic when there was minimal or not detectable drug in serum. Pretreatment with polymyxin B was successful in preventing the generalized Shwartzman reaction in rabbits and reducing endotoxin lethality in mice; however, large doses (20 mg per kg per day for 2 or 4 days) were required. Prolongation by more than 24 h of the interval between the last dose of polymyxin B and endotoxin challenge resulted in reduction or loss of protection. Dogs were unable to tolerate the high polymyxin B dosage which was protective in the mouse and rabbit. Lower, nontoxic doses of polymyxin B in dogs did not prevent endotoxin shock and lethality, even when challenged as soon as 1 h after the last dose. Pretreatment with colistimethate was ineffective in all three animal models.
在三种动物模型中，评估了多次给予多粘菌素B和粘菌素甲磺酸钠预处理后，其在组织中螯合足够抗生素以中和内毒素作用的能力。在最后一剂抗生素后24、48或72小时，当血清中抗生素含量极少或无法检测到时，用内毒素对动物进行攻击。用多粘菌素B预处理成功地预防了家兔的全身性施瓦茨曼反应，并降低了小鼠的内毒素致死率；然而，需要大剂量（每天每千克20毫克，持续2或4天）。多粘菌素B最后一剂与内毒素攻击之间的间隔延长超过24小时会导致保护作用减弱或丧失。犬无法耐受对小鼠和家兔具有保护作用的高剂量多粘菌素B。犬使用较低的无毒剂量多粘菌素B，即使在最后一剂后1小时就受到攻击，也不能预防内毒素休克和致死。在所有三种动物模型中，用粘菌素甲磺酸钠预处理均无效。
