Human Genome Sciences, Inc., 14200 Shady Grove Road, Rockville, MD 20850, USA.
Toxins (Basel). 2013 Jan 14;5(1):120-38. doi: 10.3390/toxins5010120.
Inhaled Bacillus anthracis spores germinate and the subsequent vegetative growth results in bacteremia and toxin production. Anthrax toxin is tripartite: the lethal factor and edema factor are enzymatic moieties, while the protective antigen (PA) binds to cell receptors and the enzymatic moieties. Antibiotics can control B. anthracis bacteremia, whereas raxibacumab binds PA and blocks lethal toxin effects. This study assessed plasma PA kinetics in rabbits following an inhaled B. anthracis spore challenge. Additionally, at 84 h post-challenge, 42% of challenged rabbits that had survived were treated with either levofloxacin/placebo or levofloxacin/raxibacumab. The profiles were modeled using a modified Gompertz/second exponential growth phase model in untreated rabbits, with added monoexponential PA elimination in treated rabbits. Shorter survival times were related to a higher plateau and a faster increase in PA levels. PA elimination half-lives were 10 and 19 h for the levofloxacin/placebo and levofloxacin/raxibacumab groups, respectively, with the difference attributable to persistent circulating PA-raxibacumab complex. PA kinetics were similar between untreated and treated rabbits, with one exception: treated rabbits had a plateau phase nearly twice as long as that for untreated rabbits. Treated rabbits that succumbed to disease had higher plateau PA levels and shorter plateau duration than surviving treated rabbits.
吸入炭疽芽孢后，芽孢发芽，随后的营养生长导致菌血症和毒素产生。炭疽毒素为三聚体：致死因子和水肿因子为酶部分，而保护性抗原（PA）与细胞受体结合，并与酶部分结合。抗生素可以控制炭疽杆菌菌血症，而 raxibacumab 结合 PA 并阻断致死毒素的作用。本研究评估了吸入炭疽芽孢后家兔的血浆 PA 动力学。此外，在挑战后 84 小时，42%幸存的受挑战兔子接受左氧氟沙星/安慰剂或左氧氟沙星/raxibacumab 治疗。在未治疗的兔子中，使用改良的 Gompertz/二次指数生长阶段模型对曲线进行建模，在治疗的兔子中加入单指数 PA 消除。较短的存活时间与较高的平台期和 PA 水平的快速增加有关。左氧氟沙星/安慰剂和左氧氟沙星/raxibacumab 组的 PA 消除半衰期分别为 10 和 19 小时，差异归因于持续循环的 PA-raxibacumab 复合物。未经治疗和治疗的兔子之间的 PA 动力学相似，只有一个例外：治疗的兔子的平台期几乎是未经治疗的兔子的两倍长。患病而死亡的治疗兔子的平台期 PA 水平较高，平台期持续时间较短。
