Srivastava Shashikant, Wang Jann-Yuan, Magombedze Gesham, Chapagain Moti, Huang Hung-Ling, Deshpande Devyani, Heysell Scott K, Pasipanodya Jotam G, Gumbo Tawanda
Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, Texas.
Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Antimicrob Agents Chemother. 2023 May 1;95(5). doi: 10.1128/AAC.01553-20. Epub 2021 Feb 8.
Standard therapy [isoniazid, rifampin, ethambutol], with or without a macrolide, for pulmonary 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 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] log CFU/mL/day on standard therapy. Next, we identified time-to-extinction in the hollow fiber system model of pulmonary disease [HFS-] treated with standard therapy, which was a γ of 0.60 [95% CI: 0.45-0.69) log 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- to patients. Next, a head-to-head study in the HFS- 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 disease.
用于肺结核的标准疗法[异烟肼、利福平、乙胺丁醇]，无论是否联用大环内酯类药物，疗程都超过一年。因此，需要更短疗程的治疗方案。我们使用了32例接受标准疗法治疗的台湾患者的数据，通过基于重复采样的痰液液体培养阳性时间，根据常微分方程计算杀灭斜率[γ]以及每位患者细菌负荷的灭绝时间。标准疗法下的γ为0.18[95%置信区间(CI)：0.16 - 0.20]log CFU/mL/天。接下来，我们确定了标准疗法治疗的肺结核空洞纤维系统模型[HFS-]中的灭绝时间，其γ为0.60[95%CI：0.45 - 0.69]log CFU/mL/天。两个数据集之间的γ和灭绝时间基于范畴论形成了保结构映射：因此，我们可以使用态射将它们从一个映射到另一个。这种映射确定了从HFS-到患者的灭绝时间的多步非线性转换因子。接下来，在HFS-中进行的一项对比研究确定，标准疗法的中位灭绝时间为38.7[95%CI：29.1 - 53.2]天，异烟肼 - 利福平 - 乙胺丁醇 - 莫西沙星为21.7[95%CI：19.1 - 25]天，异烟肼 - 利福平 - 莫西沙星为22[96%CI：20.1 - 24.5]天，利福平 - 莫西沙星 - 替地唑胺为20.7[95%CI：18.5 - 29]天。我们基于转换因子的翻译预测，接受标准疗法的患者在12个月时实现治愈的比例为90.7[88.74 - 92.35]%，异烟肼 - 利福平 - 乙胺丁醇 - 莫西沙星6个月的治愈率为99.8[95%CI：99.27 - 99.95]%，异烟肼 - 利福平 - 莫西沙星为92.2[90.37 - 93.71]%，利福平 - 莫西沙星 - 替地唑胺为99.9[99.44 - 99.99]%。因此，利福平 - 莫西沙星 - 替地唑胺和异烟肼 - 利福平 - 乙胺丁醇 - 莫西沙星预计是肺结核疾病的短程化疗方案。
