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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Novel short-course therapy and morphism mapping for clinical pulmonary mycobacterium kansasii
Antimicrobial Agents and Chemotherapy, Volume 65, No. 5, Article e01553-20, Year 2021
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Description
Standard therapy (isoniazid, rifampin, and 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 M. kansasii time-to-positivity in liquid cultures to calculate kill slopes (g) based on ordinary differential equations and time-to-extinction of each patient's bacterial burden. The g was 0.18 (95% confidence interval [CI] = 0.16 to 0.20) log10 CFU/ml/day on standard therapy. Next, we identified the M. kansasii time to extinction in the hollow-fiber system model of pulmonary M. kansasii disease (HFS-Mkn) treated with standard therapy, which was a g of 0.60 (95% CI = 0.45 to 0.69) log10 CFU/ml/day. The g and time-to-extinction values between the two data sets 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 nonlinear 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 to 53.2) days, isoniazid-rifampin-ethambutolmoxifloxacin therapy of 21.7 (95% CI = 19.1 to 25) days, isoniazid-rifampin-moxifloxacin therapy of 22 (96% CI = 20.1 to 24.5) days, and rifampin-moxifloxacin-tedizolid therapy of 20.7 (95% CI = 18.5 to 29) days. Our transformation-factor based translation predicted the proportion of patients of 90.7 (88.74 to 92.35)% achieving cure with standard therapy at 12 months, and 6-month cure rates of 99.8 (95% CI = 99.27 to 99.95)% for isoniazid-rifampin-ethambutol-moxifloxacin, 92.2 (90.37 to 93.71)% for isoniazid-rifampin-moxifloxacin, and 99.9 (99.44 to 99.99)% for rifampin-moxifloxacintedizolid. Thus, rifampin-moxifloxacin-tedizolid and isoniazid-rifampin-ethambutolmoxifloxacin are predicted to be short-course chemotherapy regimens for pulmonary M. kansasii disease. © 2021 American Society for Microbiology. All rights reserved.
Authors & Co-Authors
Srivastava, Shashikant
United States, Tyler
University of Texas Health Center at Tyler
United States, Dallas
Baylor University Medical Center at Dallas
United States, Dallas
Ut Southwestern Medical Center
Wang, Jannyuan
Taiwan, Taipei
National Taiwan University Hospital
Magombedze, Gesham
United States, Dallas
Baylor University Medical Center at Dallas
Chapagain, Moti L.
United States, Dallas
Baylor University Medical Center at Dallas
Huang, Hungling
Taiwan, Kaohsiung
Kaohsiung Medical University Chung-ho Memorial Hospital
Taiwan, Kaohsiung
Kaohsiung Medical University
Deshpande, Devyani
United States, Dallas
Baylor University Medical Center at Dallas
Heysell, Scott Kirkland
United States, Charlottesville
University of Virginia
Pasipanodya, Jotam Garaimunashe
United States, Dallas
Baylor University Medical Center at Dallas
Gumbo, Tawanda
United States, Dallas
Baylor University Medical Center at Dallas
United States, Dallas
Praedicare Inc.
Statistics
Citations: 6
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1128/AAC.01553-20
ISSN:
00664804
Research Areas
Cancer
Health System And Policy