Evidence map›Paper›PMID 35468189›Full record

ArticleThe Journal of antimicrobial chemotherapy2022

Drug concentration at the site of disease in children with pulmonary tuberculosis.

Elisa Lopez-Varela, Ahmed A Abulfathi, Natasha Strydom, Pierre Goussard, Abraham C van Wyk, Anne Marie Demers, Anneen Van Deventer, Anthony J Garcia-Prats, Johannes van der Merwe, Matthew Zimmerman and 11 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
0.6field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 2 syntheses or guidelines pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Aerosolization of viableProceedings of the National Academy of Sciences of the United States of America · 2024
    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

21 authors at 10 institutions in 8 countries.

Elisa Lopez-VarelaDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-6725-5687
Ahmed A AbulfathiDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-2089-3614
Natasha StrydomDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, 94158, USA.
Pierre GoussardDepartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Abraham C van WykDivision of Anatomical Pathology, Tygerberg Hospital, National Health Laboratory Service, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Anne Marie DemersDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Anneen Van DeventerDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Anthony J Garcia-PratsDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-9280-1950
Johannes van der MerweDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Matthew ZimmermanCenter for Discovery and Innovation, Hackensack Meridian Health, New Jersey, USA, and Department of Medical Sciences, Hackensack School of Medicine, Nutley, New Jersey, USA.
Claire L CarterCenter for Discovery and Innovation, Hackensack Meridian Health, New Jersey, USA, and Department of Medical Sciences, Hackensack School of Medicine, Nutley, New Jersey, USA.
Jacques JansonDivision of Cardiothoracic Surgery, Department of Surgery, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Julie MorrisonDepartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Helmuth ReuterDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Eric H DecloedtDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0003-1815-5150
James A SeddonDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Elin M SvenssonDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.
Rob WarrenDST/NRF Centre of Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Radojka M SavicDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, 94158, USA.
Véronique DartoisCenter for Discovery and Innovation, Hackensack Meridian Health, New Jersey, USA, and Department of Medical Sciences, Hackensack School of Medicine, Nutley, New Jersey, USA.
Anneke C HesselingDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Desmond Tutu HIV Foundation · ZAStellenbosch University · ZAHackensack Meridian Health · USUniversity of California, San Francisco · USWestern Cape Department of Health · ZAHackensack University Medical Center · USNational Health Laboratory Service · ZASouth African Medical Research Council · ZAUniversity of Wisconsin–Madison · USUppsala University · SE

Funding

LC - IMPAACT Leadership GroupUM1AI106716 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$47.2M
AEPDFID MR/R007942/1EDCTP TRIA.2015.1102Generalitat de CatalunyaMedical Research Council MR/R007942/1MRCNIAIDNIAID NIH HHS UM1 AI106716NIHSouth African National Research FoundationSpanish Ministry of Science and Innovation and State Research Agency CEX2018-000806-SSpanish Paediatrics Association
6 · The paper itself

Abstract

backgroundCurrent TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB.

objectivesTo determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB.

methodsWe quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions.

resultsIsoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions.

conclusionsDespite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.

Indexed as

IsoniazidTuberculosis, PulmonaryAdultAntitubercular AgentsChildEthambutolHumansInfantPyrazinamideSouth AfricaAntitubercular AgentsEthambutolIsoniazidPyrazinamide

Identifiers

PMID35468189
PMCPMC9155609
OpenAlexW4221055961

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.