当前位置: X-MOL 学术J. Infect. Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The Impact of Actotoxumab Treatment of Gnotobiotic Piglets Infected With Different Clostridium difficile Isogenic Mutants.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-02 , DOI: 10.1093/infdis/jiz459
Hillary R Danz 1 , Sangun Lee 1 , Susan P Chapman-Bonofiglio 1 , Melanie Ginese 1 , Gillian Beamer 1 , Donald J Girouard 1 , Saul Tzipori 1
Affiliation  

Nosocomial infections with Clostridium difficile are on the rise in the Unites States, attributed to emergence of antibiotic-resistant and hypervirulent strains associated with greater likelihood of recurrent infections. In addition to antibiotics, treatment with Merck anti-toxin B (TcdB) antibody bezlotoxumab is reported to reduce recurrent infections. However, treatment with anti-toxin A (TcdA) antibody actotoxumab was associated with dramatically increased disease severity and mortality rates in humans and gnotobiotic piglets. Using isogenic mutants of C. difficile strain NAPI/BI/027 deficient in TcdA (A-B+) or TcdB (A+B-), and the wild type, we investigated how and why treatment of infected animals with anti-TcdA dramatically increased disease severity. Contrary to the hypothesis, among piglets treated with anti-TcdA, those with A+B- infection were disease free, in contrast to the disease enhancement seen in those with wild-type or A-B+ infection. It seems that the lack of TcdA, through either deletion or neutralization with anti-TcdA, reduces a competitive pressure, allowing TcdB to freely exert its profound effect, leading to increased mucosal injury and disease severity.

中文翻译:

Actotoxumab处理感染艰难梭菌等基因突变体的致敏仔猪的影响。

在美国,难辨梭状芽胞杆菌的医院感染正在上升,这归因于出现抗生素耐药性和高毒力菌株,与再次感染的可能性更大有关。除抗生素外,据报道还使用默克抗毒素B(TcdB)抗体贝洛酮单抗治疗可减少复发感染。但是,抗毒素A(TcdA)抗体actotoxumab的治疗与人类和gnotobiotic仔猪的疾病严重程度和死亡率急剧增加有关。使用缺乏TcdA(A-B +)或TcdB(A + B-)和野生型的艰难梭菌NAPI / BI / 027等基因突变体,我们研究了如何以及为什么用抗TcdA治疗感染的动物疾病严重程度。与该假设相反,在用抗TcdA治疗的仔猪中,那些患有A + B-感染的人没有疾病,而那些患有野生型或A-B +感染的人却没有疾病。似乎缺乏TcdA,可以通过缺失或用抗TcdA中和来降低竞争压力,从而使TcdB自由发挥其深远的作用,从而导致粘膜损伤和疾病严重性增加。
更新日期:2019-12-30
down
wechat
bug