Nouveau short-course therapy and morphism mapping for clinical pulmonary .

Antimicrob Agents Chemother

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Published: May 2023

AI Article Synopsis

  • The study examines the effectiveness of standard therapy and alternative regimens for treating pulmonary disease, highlighting the need for shorter treatment durations.
  • Researchers analyzed data from 32 patients to calculate bacterial kill slopes and time-to-extinction using a hollow fiber system model, revealing significant differences in effectiveness between therapies.
  • The findings suggest that certain combinations, like rifampin-moxifloxacin-tedizolid, could serve as effective short-course treatment options with high rates of patient cure at 6 and 12 months.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092872PMC
http://dx.doi.org/10.1128/AAC.01553-20DOI Listing

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