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利用家蚕幼虫作为替代动物模型评估恶唑烷酮类药物的抗感染潜力。

Utilization of Bombyx mori larvae as a surrogate animal model for evaluation of the anti-infective potential of oxazolidinones.

作者信息

Barman Tarani Kanta, Arora Priya, Rao Madhvi, Bhadauriya Tripti, Upadhyay Dilip J

机构信息

Department of Infectious Diseases, New Drug Discovery Research (R & D-3), Ranbaxy Research Laboratories, Udyog Vihar Industrial Area, Plot No.20, Sector-18, Gurgaon, Haryana, 122001, India.

出版信息

J Infect Chemother. 2008 Apr;14(2):166-9. doi: 10.1007/s10156-008-0586-3.

DOI:10.1007/s10156-008-0586-3
PMID:18622683
Abstract

Silkworm (Bombyx mori) larvae were investigated as an alternative animal model for the efficacy testing of novel oxazolidinones. The minimal lethal dose (MLD) for Staphylococcus aureus was 1-5 x 10(7) CFU per larva, exhibiting more than 90% mortality within 2 to 4 days post-infection. Treatment with vancomycin, linezolid, and novel oxazolidinones (RBx 7644, RBx 8700, and RBx 2006171) showed survival in a dose-dependent manner. The antibacterial potential of RBx 7644 and RBx 8700 was compared with that of linezolid and that of vancomycin and the effective doses (ED)50 obtained in the silkworm model were 37.89, 24.96, 13.38, and 30.72 mg/kg body weight, respectively. The ED50 values showed a similar trend in a murine model of infection. Owing to the small size of the larvae, very small amounts of new chemical entities (NCEs) are required to test their in vivo efficacy in this model. Thus, the silkworm model may be used in the early stage of new discovery research.

摘要

家蚕(Bombyx mori)幼虫被作为一种新型恶唑烷酮疗效测试的替代动物模型进行了研究。金黄色葡萄球菌对家蚕幼虫的最小致死剂量(MLD)为每只幼虫1 - 5×10⁷CFU,在感染后2至4天内死亡率超过90%。用万古霉素、利奈唑胺和新型恶唑烷酮(RBx 7644、RBx 8700和RBx 2006171)进行治疗呈剂量依赖性存活。将RBx 7644和RBx 8700的抗菌潜力与利奈唑胺和万古霉素的抗菌潜力进行了比较,在家蚕模型中获得的有效剂量(ED)50分别为37.89、24.96、13.38和30.72 mg/kg体重。在小鼠感染模型中,ED50值呈现出类似的趋势。由于幼虫体积小,在该模型中测试新化学实体(NCEs)的体内疗效所需的新化学实体量非常少。因此,家蚕模型可用于新发现研究的早期阶段。

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