ArticleFrontiers in pharmacology2020
Both Pharmacokinetic Variability and Granuloma Heterogeneity Impact the Ability of the First-Line Antibiotics to Sterilize Tuberculosis Granulomas.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- A Comparison of Mechanisms Driving Lesion Outcomes During Lung Tumor and Tuberculosis Granuloma Formation.Bulletin of mathematical biology · 2026Article
- An adenylyl cyclase switch reroutes carbon from growth to virulence lipids inbioRxiv : the preprint server for biology · 2026Article
- Article
- Host oxidative stress primes mycobacteria for rapid antibiotic resistance evolution.Nature communications · 2026Article
- Necro-mosaic: a lesion-aware framework for testing programmed cell-death-associated mechanisms in tuberculosis.Frontiers in immunology · 2026Review
- Advancing Tuberculosis Treatment with Next-Generation Drugs and Smart Delivery Systems.Pharmaceutics · 2026Review
- Host oxidative stress primes mycobacteria for rapid antibiotic resistance evolution.Research square · 2025Article
- Article
- A novel machine-learning based optimization: identifying new treatment regimens for tuberculosis.Numerical algebra, control and optimization · 2025Article
- Distinguishing multiple roles of T cell and macrophage involvement in determining lymph node fates during Mycobacterium tuberculosis infection.PLoS computational biology · 2025Article
- GEODE: anFrontiers in pharmacology · 2025Article
- A Comparative Pharmacokinetics Study of Orally and Intranasally Administered 8-Nitro-1,3-benzothiazin-4-one (BTZ043) Amorphous Drug Nanoparticles.ACS pharmacology & translational science · 2024Article
- [Characterization of a 3-dimensional tuberculosis spheroid model constructed using human monocytic THP-1 cells andNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens.PLoS computational biology · 2023Article
- The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy.eLife · 2023Article
- A framework for multi-scale intervention modeling: virtual cohorts, virtual clinical trials, and model-to-model comparisons.Frontiers in systems biology · 2023Article
- Concomitant immunity to M. tuberculosis infection.Scientific reports · 2022Article
- Microfluidic dose-response platform to track the dynamics of drug response in single mycobacterial cells.Scientific reports · 2022Article
- A virtual host model of Mycobacterium tuberculosis infection identifies early immune events as predictive of infection outcomes.Journal of theoretical biology · 2022Article
- A Review: Antimicrobial Therapy for Human Pythiosis.Antibiotics (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberculosis (TB) remains as one of the world's deadliest infectious diseases despite the use of standardized antibiotic therapies. Recommended therapy for drug-susceptible TB is up to 6 months of antibiotics. Factors that contribute to lengthy regimens include antibiotic underexposure in lesions due to poor pharmacokinetics (PK) and complex granuloma compositions, but it is difficult to quantify how individual antibiotics are affected by these factors and to what extent these impact treatments. We use our next-generation multi-scale computational model to simulate granuloma formation and function together with antibiotic pharmacokinetics and pharmacodynamics, allowing us to predict conditions leading to granuloma sterilization. In this work, we focus on how PK variability, determined from human PK data, and granuloma heterogeneity each quantitatively impact granuloma sterilization. We focus on treatment with the standard regimen for TB of four first-line antibiotics: isoniazid, rifampin, ethambutol, and pyrazinamide. We find that low levels of antibiotic concentration due to naturally occurring PK variability and complex granulomas leads to longer granuloma sterilization times. Additionally, the ability of antibiotics to distribute in granulomas and kill different subpopulations of bacteria contributes to their specialization in the more efficacious combination therapy. These results can inform strategies to improve antibiotic therapy for TB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.