https://scholars.lib.ntu.edu.tw/handle/123456789/586163
標題: | Novel short-course therapy and morphism mapping for clinical pulmonary mycobacterium kansasii | 作者: | Srivastava, Shashikant JANN-YUAN WANG Magombedze, Gesham Chapagain, Moti Huang, Hung-Ling Deshpande, Devyani Heysell, Scott K Pasipanodya, Jotam G Gumbo, Tawanda |
關鍵字: | Hollow-fiber system | Moxifloxacin | Tedizolid | Time to extinction | Treatment duration | 公開日期: | 8-二月-2021 | 卷: | 65 | 期: | 5 | 來源出版物: | Antimicrobial agents and chemotherapy | 摘要: | Standard therapy [isoniazid, rifampin, ethambutol], with or without a macrolide, for pulmonary Mycobacterium kansasii lasts more than a year. Therefore, shorter treatment duration regimens are required. We used data from 32 Taiwanese patients treated with standard therapy who were followed using repetitive sampling-based sputum Mkn time-to-positivity in liquid cultures to calculate kill slopes [γ] based on ordinary differential equations and time-to-extinction of each patient's bacterial burden. The γ was 0.18 [95% Confidence Interval (CI): 0.16-0.20] log10 CFU/mL/day on standard therapy. Next, we identified Mkn time-to-extinction in the hollow fiber system model of pulmonary M. kansasii disease [HFS-Mkn] treated with standard therapy, which was a γ of 0.60 [95% CI: 0.45-0.69) log10 CFU/mL/day. The γs and time-to-extinctions between the two datasets formed structure-preserving maps based on category theory: thus, we could map them from one to the other using morphisms. This mapping identified a multistep non-linear transformation-factor for time-to-extinction from HFS-Mkn to patients. Next, a head-to-head study in the HFS-Mkn identified median time-to-extinction for standard therapy of 38.7 [95% CI: 29.1-53.2) days, isoniazid-rifampin-ethambutol-moxifloxacin of 21.7 [95% CI: 19.1-25) days, isoniazid-rifampin-moxifloxacin of 22 [96% CI: 20.1-24.5) days, and rifampin-moxifloxacin-tedizolid of 20.7 [95% CI:18.5-29) days. Our transformation-factor based translation predicted the proportion of patients of 90.7 [88.74-92.35)% achieving cure with standard therapy at 12 months, and 6-months cure rates of 99.8 [95% CI: 99.27-99.95)% for isoniazid-rifampin-ethambutol-moxifloxacin, 92.2 [90.37-93.71)% for isoniazid-rifampin-moxifloxacin, and 99.9 [99.44-99.99)% for rifampin-moxifloxacin-tedizolid. Thus, rifampin-moxifloxacin-tedizolid and isoniazid-rifampin-ethambutol-moxifloxacin are predicted to be short-course chemotherapy regimens for pulmonary M. kansasii disease. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/586163 | ISSN: | 00664804 | DOI: | 10.1128/AAC.01553-20 | SDG/關鍵字: | ethambutol; isoniazid; macrolide; moxifloxacin; quinolone derivative; rifabutin; rifampicin; tedizolid; adult; aged; Article; bacterial clearance; bacterial load; bacterium identification; clinical article; cohort analysis; colony forming unit; controlled study; disease burden; drug megadose; female; follow up; human; human tissue; lung tuberculosis; male; mathematical analysis; minimum inhibitory concentration; morphism mapping; multicenter study; Mycobacterium kansasii; priority journal; short course therapy; Taiwanese; treatment duration; treatment indication; very elderly |
顯示於: | 醫學系 |
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