Evidence map›Paper›PMID 37319311›Full record

ArticlePLoS computational biology2023

Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens.

Maral Budak, Joseph M Cicchese, Pauline Maiello, H Jacob Borish, Alexander G White, Harris B Chishti, Jaime Tomko, L James Frye, Daniel Fillmore, Kara Kracinovsky and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. bioRxiv : the preprint server for biology · 2026
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  9. Control of medical digital twins with artificial neural networks.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025
    Article
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  13. GEODE: anFrontiers in pharmacology · 2025
    Article
  14. Article
  15. Article
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  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Maral BudakDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-7934-4230
Joseph M CiccheseDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
Pauline MaielloDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
H Jacob BorishDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Alexander G WhiteDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Harris B ChishtiDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Jaime TomkoDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
L James FryeDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Daniel FillmoreDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Kara KracinovskyDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Jennifer SakalDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Charles A ScangaDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Philana Ling LinDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Véronique DartoisCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, United States of America.
Jennifer J LindermanDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
JoAnne L FlynnDepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0001-7874-8981
Denise E KirschnerDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-1053-2591
University of Pittsburgh · USUniversity of Michigan · USHackensack Meridian Health · US

Funding

A Multi-scale systems pharmacology approach to TB therapyU01HL131072 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DARTOIS, VERONIQUE, FLYNN, JOANNE L. · 2016 to 2019
$2.9M
High-Performance Computing Cluster for Biomedical ResearchS10OD026825 · OD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ATHEY, BRIAN DAVID · 2020 to 2020
$600k
A QTRAP 6500 LC-MS/MS System from SCIEX for high accuracy drug content analysisS10OD023524 · OD · RBHS-NEW JERSEY MEDICAL SCHOOL · PI DARTOIS, VERONIQUE · 2017 to 2017
$526k
NHLBI NIH HHS U01 HL131072NIH HHS S10 OD023524NIH HHS S10 OD026825Wellcome Trust
6 · The paper itself

Abstract

Tuberculosis (TB) continues to be one of the deadliest infectious diseases in the world, causing ~1.5 million deaths every year. The World Health Organization initiated an End TB Strategy that aims to reduce TB-related deaths in 2035 by 95%. Recent research goals have focused on discovering more effective and more patient-friendly antibiotic drug regimens to increase patient compliance and decrease emergence of resistant TB. Moxifloxacin is one promising antibiotic that may improve the current standard regimen by shortening treatment time. Clinical trials and in vivo mouse studies suggest that regimens containing moxifloxacin have better bactericidal activity. However, testing every possible combination regimen with moxifloxacin either in vivo or clinically is not feasible due to experimental and clinical limitations. To identify better regimens more systematically, we simulated pharmacokinetics/pharmacodynamics of various regimens (with and without moxifloxacin) to evaluate efficacies, and then compared our predictions to both clinical trials and nonhuman primate studies performed herein. We used GranSim, our well-established hybrid agent-based model that simulates granuloma formation and antibiotic treatment, for this task. In addition, we established a multiple-objective optimization pipeline using GranSim to discover optimized regimens based on treatment objectives of interest, i.e., minimizing total drug dosage and lowering time needed to sterilize granulomas. Our approach can efficiently test many regimens and successfully identify optimal regimens to inform pre-clinical studies or clinical trials and ultimately accelerate the TB regimen discovery process.

Indexed as

TuberculosisTuberculosis, Multidrug-ResistantAnimalsAntitubercular AgentsMiceMoxifloxacinAntitubercular AgentsMoxifloxacin

Identifiers

PMID37319311
PMCPMC10306236
OpenAlexW4380853449

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.