Evidence map›Paper›PMID 27351427›Full record

ArticlePharmaceutical research2016

Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis.

E F Young, E Perkowski, S Malik, J D Hayden, P G Durham, L Zhong, J T Welch, Miriam S Braunstein, Anthony J Hickey

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
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

9 authors at 3 institutions in 1 country.

E F YoungDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
E PerkowskiDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
S MalikDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
J D HaydenDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
P G DurhamRTI International, 3040 Cornwallis Road, Research Triangle Park, North Carolina, 27709, USA.
L ZhongDepartment of Chemistry, University of Albany, State University of New York, Albany, New York, 12222, USA.
J T WelchDepartment of Chemistry, University of Albany, State University of New York, Albany, New York, 12222, USA.
Miriam S BraunsteinDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA. miriam_braunstein@med.unc.edu.
Anthony J HickeyRTI International, 3040 Cornwallis Road, Research Triangle Park, North Carolina, 27709, USA. ahickey@rti.org.
University of North Carolina at Chapel Hill · USRTI International · USUniversity at Albany, State University of New York · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
NIAID NIH HHS UM1 AI068636
6 · The paper itself

Abstract

purposeAnalog development of existing drugs and direct drug delivery to the lungs by inhalation as treatments for multiple and extensively drug resistant (MDR and XDR) tuberculosis (TB) represent new therapeutic strategies. Pyrazinamide (PZA) is critical to drug sensitive TB therapy and is included in regimens for MDR TB. However, PZA-resistant Mycobacterium tuberculosis (Mtb) strains threaten its use. Pyrazinoic acid esters (PAEs) are PZA analogs effective against Mtb in vitro, including against the most common PZA resistant strains. However, PAEs require testing for TB efficacy in animal models.

methodsPAEs were delivered daily as aqueous dispersions from a vibrating mesh nebulizer to Mtb infected guinea pigs for 4 weeks in a regimen including orally administered first-line TB drugs.

resultsPAEs tested as a supplement to oral therapy significantly reduced the organ bacterial burden in comparison to infected, untreated control animals. Thus, PAE aerosol therapy is a potentially significant addition to the regimen for PZA resistant MDR-TB and XDR-TB treatment. Interestingly, low dose oral PZA treatment combined with standard therapy also reduced bacterial burden. This observation may be important for PZA susceptible disease treatment.

conclusionThe present study justifies further evaluation of PZA analogs and their lung delivery to treat TB.

Indexed as

Administration, InhalationAerosolsAnimalsAntitubercular AgentsEstersGuinea PigsMaleMicrobial Sensitivity TestsMycobacterium tuberculosisPyrazinamideTreatment OutcomeTuberculosisTuberculosis, Multidrug-ResistantAerosolsAntitubercular AgentsEstersPyrazinamidepyrazinoic acidinhaled therapypyrazinoic acidpyrazinoic acid estersTB drugstuberculosis

Identifiers

PMID27351427
OpenAlexW2463635937

What OpenQuestion holds

Textmetadata
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.