Evidence map›Paper›PMID 32016320›Full record

ArticleThe Journal of antimicrobial chemotherapy2020

Discordances between molecular assays for rifampicin resistance in Mycobacterium tuberculosis: frequency, mechanisms and clinical impact.

Annelies Van Rie, Michael G Whitfield, Elise De Vos, Lesley Scott, Pedro Da Silva, Cindy Hayes, Tim H Heupink, Frederick A Sirgel, Wendy Stevens, Robin M Warren

Open access · greenAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

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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

10 authors at 4 institutions in 2 countries.

Annelies Van RieDepartment of Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
Michael G WhitfieldDepartment of Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
Elise De VosDepartment of Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
Lesley ScottDepartment of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Pedro Da SilvaNational Health Laboratory Services, Johannesburg, South Africa.
Cindy HayesNational Health Laboratory Services, Port Elizabeth, South Africa.
Tim H HeupinkDepartment of Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
Frederick A SirgelSouth African Medical Research Council Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Stellenbosch, South Africa.
Wendy StevensNational Health Laboratory Services, Johannesburg, South Africa.
Robin M WarrenSouth African Medical Research Council Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Stellenbosch, South Africa.
National Health Laboratory Service · ZASouth African Medical Research Council · ZAUniversity of Antwerp · BEUniversity of the Witwatersrand · ZA

Funding

Optimizing the impact of Xpert MTB/RIF on treatment outcomes of drug resistant TBR01AI099026 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAN RIE, ANNELIES T.A. · 2012 to 2014
$1.6M
Medical Research Council MC_PC_16021NIAID NIH HHS R01 AI099026
6 · The paper itself

Abstract

backgroundMolecular assays are endorsed for detection and confirmation of rifampicin-resistant TB. The frequency, causal mechanisms and impact of discordant results between molecular tests are not well understood.

methodsThe prevalence of discordant results was determined by pairwise comparison of molecular test results in a cohort of 749 rifampicin-resistant TB patients in three South African provinces. Culture isolates were sent to a research laboratory for WGS and rifampicin MIC determination. Clinical information was collected through medical file review.

resultsThe prevalence of discordances between Xpert MTB/RIF and MTBDRplus was 14.5% (95% CI 10.9%-18.9%), 5.6% (95% CI 2.2%-13.4%) between two consecutive Xpert assays and 4.2% (95% CI 2.2%-7.8%) between two consecutive MTBDRplus assays. Likely mechanisms of discordances were false rifampicin susceptibility on MTBDRplus (due to variants not included in mutant probes or heteroresistance with loss of minor variants in culture), false resistance on molecular assay in rifampicin-susceptible isolates, and human error. The healthcare worker changed the treatment regimen in 33% of patients with discordant results and requested 232 additional molecular tests after a first confirmatory test was performed in 460 patients. A follow-up Xpert assay would give the healthcare worker the 'true' rifampicin-resistant TB diagnosis in at least 73% of discordant cases.

conclusionsThe high rate of discordant results between Xpert and MTBDRplus has important implications for the laboratory, clinician and patient. While root causes for discordant result are multiple, a follow-up Xpert assay could guide healthcare workers to the correct treatment in most patients.

Indexed as

Antibiotics, AntitubercularMycobacterium tuberculosisTuberculosis, Multidrug-ResistantDrug Resistance, BacterialHumansRifampinSensitivity and SpecificityAntibiotics, AntitubercularRifampin

Identifiers

PMID32016320
PMCPMC8453393
OpenAlexW3012674109

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.