Evidence map›Paper›PMID 26927983›Full record

ArticleInternational journal of mycobacteriology2016

Correlating rrs and eis promoter mutations in clinical isolates of Mycobacterium tuberculosis with phenotypic susceptibility levels to the second-line injectables.

Priti Kambli, Kanchan Ajbani, Chaitali Nikam, Meeta Sadani, Anjali Shetty, Zarir Udwadia, Sophia B Georghiou, Timothy C Rodwell, Antonino Catanzaro, Camilla Rodrigues

Erratum issuedOpen access · diamondAbstract read
In one paragraph

Article in International journal of mycobacteriology, 2016. 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 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 62 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Priti KambliMicrobiology Section, Department of Laboratory Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Kanchan AjbaniMicrobiology Section, Department of Laboratory Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Chaitali NikamMicrobiology Section, Department of Laboratory Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Meeta SadaniMicrobiology Section, Department of Laboratory Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Anjali ShettyMicrobiology Section, Department of Laboratory Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Zarir UdwadiaPulmonology Section, Department of Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India.
Sophia B GeorghiouDepartment of Medicine, University of California, San Diego, San Diego, CA, United States.
Timothy C RodwellDepartment of Medicine, University of California, San Diego, San Diego, CA, United States.
Antonino CatanzaroDepartment of Medicine, University of California, San Diego, San Diego, CA, United States.
Camilla RodriguesMicrobiology Section, Department of Laboratory Medicine, P. D. Hinduja Hospital & Medical Research Centre, Mumbai, India. Electronic address: dr_crodrigues@hindujahospital.com.
P. D. Hinduja Hospital and Medical Research Centre · INUniversity of California, San Diego · US

Funding

Rapid Tests for Drug Resistance to Detect Extensively Drug-Resistant TuberculosisU01AI082229 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CATANZARO, ANTONINO · 2009 to 2013
$10.9M
An Integrated Tabletop Platform for Rapid Detection of XDR-TB in Clinical SamplesR01AI111435 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RODWELL, TIMOTHY CHARLES · 2014 to 2018
$5.4M
NIAID NIH HHS R01 AI111435NIAID NIH HHS U01 AI082229NIAID NIH HHS U01-AI082229PHS HHS R01-A111435-04
6 · The paper itself

Abstract

OBJECTIVE/

backgroundThe in vitro drug-susceptibility testing of Mycobacterium tuberculosis reports isolates as resistant or susceptible on the basis of single critical concentrations. It is evident that drug resistance in M. tuberculosis is quite heterogeneous, and involves low level, moderate level, and high level of drug-resistant phenotypes. Thus, the aim of our study was to correlate rrs (X52917) and eis (AF144099) promoter mutations, found in M. tuberculosis isolates, with corresponding minimum inhibitory concentrations of amikacin, kanamycin, and capreomycin.

methodsNinety M. tuberculosis clinical isolates were analyzed in this study. The minimum inhibitory concentrations were determined by MGIT 960 for 59 isolates with resistance-associated mutations in the rrs and eis promoter gene regions, and 31 isolates with wild-type sequences, as determined by the GenoType MTBDRsl (version 1) assay.

resultsThe rrs A1401G mutation was identified in 48 isolates resistant to the second-line injectables. The eis promoter mutations C-14T (n=3), G-10C (n=3), G-10A (n=3), and C-12T (n=2) were found within 11 isolates with various resistance profiles to the second-line injectables. Thirty-one isolates had wild-type sequences for the rrs and eis promoter gene regions of interest, one of which was amikacin, kanamycin, and capreomycin resistant. The isolates with the rrs A1401G mutation had amikacin, kanamycin, and capreomycin minimum inhibitory concentrations of >40mg/L, >20mg/L, and 5-15mg/L, respectively. The isolates with eis promoter mutations had amikacin, kanamycin, and capreomycin minimum inhibitory concentrations of 0.25-1.0mg/L, 0.625-10mg/L, and 0.625-2.5mg/L, respectively.

conclusionThis study provides a preliminary basis for the prediction of phenotypic-resistance levels to the second-line injectables based upon the presence of genetic mutations associated with amikacin, kanamycin, and capreomycin resistance. The results suggest that isolates with eis promoter mutations have consistently lower resistance levels to amikacin, kanamycin, and capreomycin than isolates with the rrs A1401G mutation.

Indexed as

Promoter Regions, GeneticAcetyltransferasesAmikacinAnti-Bacterial AgentsAntigens, BacterialBacterial ProteinsCapreomycinDrug Resistance, Multiple, BacterialGenes, rRNAGenotypeHumansKanamycinMicrobial Sensitivity TestsMutationMycobacterium tuberculosisPhenotypeAcetyltransferasesAmikacinAnti-Bacterial AgentsAntigens, BacterialBacterial ProteinsCapreomycinEis protein, Mycobacterium tuberculosisKanamycinRNA, Ribosomal, 16SDrug-susceptibility testingExtremely drug-resistant tuberculosisLevel of resistanceMutations

Identifiers

PMID26927983
PMCPMC4863938
OpenAlexW1853183029

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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.