Evidence map›Paper›PMID 30261007›Full record

ArticlePloS one2018

Efficacy of pyrazinoic acid dry powder aerosols in resolving necrotic and non-necrotic granulomas in a guinea pig model of tuberculosis.

Stephanie A Montgomery, Ellen F Young, Phillip G Durham, Katelyn E Zulauf, Laura Rank, Brittany K Miller, Jennifer D Hayden, Feng-Chang Lin, John T Welch, Anthony J Hickey and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
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  4. Article
  5. One Size Fits All? Not inFrontiers in cellular and infection microbiology · 2021
    Review
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  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Stephanie A MontgomeryDepartment of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Ellen F YoungDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Phillip G DurhamRTI International, Research Triangle Park, North Carolina, United States of America.
Katelyn E ZulaufDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Laura RankDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Brittany K MillerDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Jennifer D HaydenDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Feng-Chang LinDepartment of Biostatistics and North Carolina Translational and Clinical Sciences Institute, University of North Carolina, Chapel Hill, North Carolina, United States of America.
John T WelchDepartment of Chemistry, University at Albany, Albany, New York, United States of America.
Anthony J HickeyRTI International, Research Triangle Park, North Carolina, United States of America.
Miriam BraunsteinDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID 0000-0003-1180-0030
University of North Carolina at Chapel Hill · USRTI International · USUniversity at Albany, State University of New York · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
North Carolina Translational & Clinical Sciences Institute (NC TraCS)UL1TR001111 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, CAREY, TIMOTHY S · 2013 to 2017
$43.9M
NCATS NIH HHS UL1 TR001111NCATS NIH HHS UL1 TR002489NCI NIH HHS P30 CA016086
6 · The paper itself

Abstract

New therapeutic strategies are needed to treat drug resistant tuberculosis (TB) and to improve treatment for drug sensitive TB. Pyrazinamide (PZA) is a critical component of current first-line TB therapy. However, the rise in PZA-resistant TB cases jeopardizes the future utility of PZA. To address this problem, we used the guinea pig model of TB and tested the efficacy of an inhaled dry powder combination, referred to as Pyrazinoic acid/ester Dry Powder (PDP), which is comprised of pyrazinoic acid (POA), the active moiety of PZA, and pyrazinoic acid ester (PAE), which is a PZA analog. Both POA and PAE have the advantage of being able to act on PZA-resistant Mycobacterium tuberculosis. When used in combination with oral rifampicin (R), inhaled PDP had striking effects on tissue pathology. Effects were observed in lungs, the site of delivery, but also in the spleen and liver indicating both local and systemic effects of inhaled PDP. Tissue granulomas that harbor M. tuberculosis in a persistent state are a hallmark of TB and they pose a challenge for therapy. Compared to other treatments, which preferentially cleared non-necrotic granulomas, R+PDP reduced necrotic granulomas more effectively. The increased ability of R+PDP to act on more recalcitrant necrotic granulomas suggests a novel mechanism of action. The results presented in this report reveal the potential for developing therapies involving POA that are optimized to target necrotic as well as non-necrotic granulomas as a means of achieving more complete sterilization of M. tuberculosis bacilli and preventing disease relapse when therapy ends.

Indexed as

AerosolsAnimalsAntitubercular AgentsBacterial LoadDisease Models, AnimalDrug Therapy, CombinationDry Powder InhalersGranuloma, Respiratory TractGuinea PigsMaleMycobacterium tuberculosisNecrosisPyrazinamideRespiratory Tract AbsorptionRifampinTuberculosis, Multidrug-ResistantAerosolsAntitubercular AgentsPyrazinamidepyrazinoic acidRifampin

Identifiers

PMID30261007
PMCPMC6160074
OpenAlexW2893259841

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.