Evidence map›Paper›PMID 25339395›Full record

ArticleJournal of clinical microbiology2015

Genotypic susceptibility testing of Mycobacterium tuberculosis isolates for amikacin and kanamycin resistance by use of a rapid sloppy molecular beacon-based assay identifies more cases of low-level drug resistance than phenotypic Lowenstein-Jensen testing.

Soumitesh Chakravorty, Jong Seok Lee, Eun Jin Cho, Sandy S Roh, Laura E Smith, Jiim Lee, Cheon Tae Kim, Laura E Via, Sang-Nae Cho, Clifton E Barry and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of clinical microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.1field-weighted citation impact, top 8% 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, 40 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

11 authors at 5 institutions in 2 countries.

Soumitesh ChakravortyDepartment of Medicine, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA chakraso@njms.rutgers.edu.
Jong Seok LeeDepartment of Microbiology, International Tuberculosis Research Center, Changwon, Gyeongsang, Republic of Korea.
Eun Jin ChoDepartment of Microbiology, International Tuberculosis Research Center, Changwon, Gyeongsang, Republic of Korea.
Sandy S RohDepartment of Medicine, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Laura E SmithDepartment of Medicine, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Jiim LeeDepartment of Microbiology, International Tuberculosis Research Center, Changwon, Gyeongsang, Republic of Korea.
Cheon Tae KimNational Masan Tuberculosis Hospital, Changwon, Republic of Korea.
Laura E ViaTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Sang-Nae ChoDepartment of Microbiology, International Tuberculosis Research Center, Changwon, Gyeongsang, Republic of Korea Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University, College of Medicine, Seoul, Republic of Korea.
Clifton E BarryTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
David AllandDepartment of Medicine, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Rutgers, The State University of New Jersey · USInternational Tuberculosis Research Center · KRNational Institute of Allergy and Infectious Diseases · USMasan National Tuberculosis Hospital · KRYonsei University · KR

Funding

Exploring the metabolism of non-replicating and drug-resistant TBZIAAI000783 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$8.2M
Development of a second generation MDR-XDR TB assayU01AI082174 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI ALLAND, DAVID · 2009 to 2013
$7.2M
International Research in Korea: Clinical Studies of Drug-Resistant TuberculosisZIAAI001067 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$6.9M
Rapid Diagnosis of XDR TuberculosisR01AI080653 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI ALLAND, DAVID · 2009 to 2013
$2.8M
Intramural NIH HHSNIAID NIH HHS AI080653NIAID NIH HHS AI082174NIAID NIH HHS R01 AI080653NIAID NIH HHS U01 AI082174
6 · The paper itself

Abstract

Resistance to amikacin (AMK) and kanamycin (KAN) in clinical Mycobacterium tuberculosis strains is largely determined by specific mutations in the rrs gene and eis gene promoter. We developed a rapid, multiplexed sloppy molecular beacon (SMB) assay to identify these mutations and then evaluated assay performance on 603 clinical M. tuberculosis DNA samples collected in South Korea. Assay performance was compared to gold-standard phenotypic drug susceptibility tests, including Lowenstein-Jensen (LJ) absolute concentration, mycobacterial growth indicator tubes (MGIT), and TREK Sensititre MycoTB MIC plate (MycoTB) methods. Target amplicons were also tested for mutations by Sanger sequencing. The SMB assay correctly detected 115/116 mutant and mixed sequences and 487/487 wild-type sequences (sensitivity and specificity of 99.1 and 100%, respectively). Using the LJ method as the reference, sensitivity and specificity for AMK resistance were 92.2% and 100%, respectively, and sensitivity and specificity for KAN resistance were 87.7% and 95.6%, respectively. Mutations in the rrs gene were unequivocally associated with high-level cross-resistance to AMK and KAN in all three conventional drug susceptibility testing methods. However, eis promoter mutations were associated with KAN resistance using the MGIT or MycoTB methods but not the LJ method. No testing method associated eis promoter mutations with AMK resistance. Among the discordant samples with AMK and/or KAN resistance but wild-type sequence at the target genes, we discovered four new mutations in the whiB7 5' untranslated region (UTR) in 6/22 samples. All six samples were resistant only to KAN, suggesting the possible role of these whiB7 5' UTR mutations in KAN resistance.

Indexed as

Drug Resistance, Multiple, BacterialGenotyping TechniquesMicrobial Sensitivity TestsAmikacinAnti-Bacterial AgentsGenes, BacterialHumansKanamycin ResistanceMutationMycobacterium tuberculosisReproducibility of ResultsSensitivity and SpecificitySequence Analysis, DNATuberculosisTuberculosis, Multidrug-ResistantAmikacinAnti-Bacterial Agents

Identifiers

PMID25339395
PMCPMC4290905
OpenAlexW2019129341

What OpenQuestion holds

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Registered trials

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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.