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在小鼠模型中评估新型抗菌药物及其组合,以确定麻风病的短疗程替代化疗方案。

Evaluation of New Antibacterial Drugs and their Combinations in a Murine Model to Identify Short Duration Alternative Chemotherapy for Leprosy.

作者信息

Arumugam S, Joseph P, Ponnaiya J, Richard J, Das M, Chaitanya V S, Ebenezer M

出版信息

Indian J Lepr. 2016 Jul-Sep;88(3):159-76.

Abstract

The objective of the research is to test the efficacy of new drugs and drug combinations in mice infected with Mycobacterium leprae (M. leprae) as alternative to current WHO MDT. Individual drugs tested were Rifampicin (RMP), Rifapentine (RPT) and Moxifloxacin (MOXI). Drug combinations were RMP, Clarithromycin (CLARI), Minocycline (MINO) and RMP, MINO and Ofloxacin (OFLO). RPT drug combinations were RPT, CLARI, MINO and RPT, OFLO, MINO. Both the drugs and drug combinations were used as daily regimen and intermittent regimen. WHO MB MDT served as a positive control. Mice pre-inoculated with M. leprae were allotted to daily and intermittent groups and administered selected drugs and drug combinations. At the end of 12 months post sub-inoculation, mice were sacrificed and the proportion % of viable bacilli were counted using Spearman and Karber method. It was noted that RMP, RPT and Moxifloxacin indicated a range of 89.99% to 99.99% bactericidal effect when used in daily or intermittent doses in both normal and TR mice. Drug combinations showed bactericidal effect comparable to that of WHO MDT. From the study it was concluded that if the present duration of MDT has to be shortened then daily dose regimen with RMP/MINO/OFLO or RPT/CLARI/MINO are recommended for a clinical trial.

摘要

该研究的目的是测试新药及药物组合对感染麻风分枝杆菌(M. leprae)小鼠的疗效,作为世界卫生组织现行多药联合化疗(MDT)的替代方案。所测试的单一药物为利福平(RMP)、利福喷汀(RPT)和莫西沙星(MOXI)。药物组合为RMP、克拉霉素(CLARI)、米诺环素(MINO)以及RMP、MINO和氧氟沙星(OFLO)。RPT药物组合为RPT、CLARI、MINO以及RPT、OFLO、MINO。药物及药物组合均采用每日给药方案和间歇给药方案。世界卫生组织的MB MDT作为阳性对照。预先接种了麻风分枝杆菌的小鼠被分配到每日给药组和间歇给药组,并给予选定的药物及药物组合。在再次接种后12个月结束时,处死小鼠,使用Spearman和Karber方法计算存活杆菌的比例(%)。结果表明,RMP、RPT和莫西沙星在正常小鼠和TR小鼠中以每日或间歇剂量使用时,杀菌效果在89.99%至99.99%之间。药物组合显示出与世界卫生组织MDT相当的杀菌效果。从该研究得出结论,如果必须缩短目前MDT的疗程,那么建议在临床试验中采用RMP/MINO/OFLO或RPT/CLARI/MINO的每日剂量方案。

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