非达霉素和万古霉素对黄金地鼠艰难梭菌相关性腹泻动物模型治疗效果的评价

Evaluation of the in vivo efficacy of fidaxomicin and vancomycin in a hamster model of Clostridium difficile-associated diarrhea

目的评价非达霉素和万古霉素对黄金地鼠艰难梭菌相关性腹泻动物模型的体内抗菌作用。方法以4×107CFU/m L的艰难梭菌ATCC BAA^(-1)870感染黄金地鼠后,用不同浓度的非达霉素(0.3、0.8和2.5 mg·kg^(-1)·d^(-1))或者万古霉素(5 mg·kg^(-1)·d^(-1))灌胃,观察给药后黄金地鼠的体质量变化和存活率。结果在艰难梭菌ATCC BAA^(-1)870感染后,用非达霉素和万古霉素治疗7 d期间,动物生存率为100%。非达霉素(2.5 mg·kg^(-1)·d^(-1))治疗组一直到观察终点生存率为100%,但是万古霉素组在观察第11天时出现感染复发并死亡,观察到30 d时生存率仅为20%。粪便培养显示非达霉素可以有效清除黄金地鼠粪便中的艰难梭菌。结论非达霉素对高产毒艰难梭菌具有强效的体内抗菌作用,与目前临床常用万古霉素相比,其治疗复发率低,值得进一步在临床上试验。

Objective To assess the relative efficacy offidaxomicin and vancomycin in the hamster model of Clostridium diJflcile- associated diarrhea （CDAD）. Methods Hamsters were infected with C. difficile ATCC BAA-1870 （ribotype 027, 4× 107 CFU/mL） prior to treatment with fidaxomicin （0.3 mg. kg-1 d-1, 0.8 mg kg-1 d-1 and 2.5 mg kg-1 - d-l） or vancomycin （5 mg kg-1 d-1） for 7 days. Animals were further monitored through day 30 to record weight change and survival status. Results Following infection with C. difficile ATCC BAA-1870, fidaxomicin and vancomycin treatment resulted in 100% survival during the 7-day dosing period. All the animals receiving fidaxomicin （2.5 mgkg-1 d-1） survived until end of post-dosing follow-up period. However, mortality was observed on day ! 1 in the animals treated with vancomycin, and the survival rate was 20% by day 30. Stool culture showed that fidaxomicin can effectively remove Clostridium difficile from the feces of hamster. Conelusions Compared with vancomycin, fidaxomicin is highly effective in treatment of both acute infection and prevention of recurrent disease. It is worthwhile to design further investigation on fidaxomicin as a potential therapy for CDAD.