Cryptic Resistance Mutations Associated With Misdiagnoses of Multidrug-Resistant Tuberculosis.
Antitubercular Agents
/ therapeutic use
Bacterial Proteins
/ genetics
Diagnostic Errors
/ prevention & control
Drug Resistance, Multiple, Bacterial
/ genetics
Extensively Drug-Resistant Tuberculosis
/ drug therapy
Genome, Bacterial
/ genetics
Genotype
Humans
Isoniazid
/ therapeutic use
Microbial Sensitivity Tests
/ methods
Mutation
/ genetics
Mycobacterium tuberculosis
/ drug effects
Rifampin
/ therapeutic use
Sequence Analysis, DNA
/ methods
Tuberculosis, Multidrug-Resistant
/ genetics
Whole Genome Sequencing
/ methods
Tuberculosis
cryptic mutations
drug resistance
individualized treatment
whole-genome sequencing
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
19 06 2019
19 06 2019
Historique:
received:
19
11
2018
accepted:
11
03
2019
pubmed:
16
3
2019
medline:
25
2
2020
entrez:
16
3
2019
Statut:
ppublish
Résumé
Understanding why some multidrug-resistant tuberculosis cases are not detected by rapid phenotypic and genotypic routine clinical tests is essential to improve diagnostic assays and advance toward personalized tuberculosis treatment. Here, we combine whole-genome sequencing with single-colony phenotyping to identify a multidrug-resistant strain that had infected a patient for 9 years. Our investigation revealed the failure of rapid testing and genome-based prediction tools to identify the multidrug-resistant strain. The false-negative findings were caused by uncommon rifampicin and isoniazid resistance mutations. Although whole-genome sequencing data helped to personalize treatment, the patient developed extensively drug-resistant tuberculosis, highlighting the importance of coupling new diagnostic methods with appropriate treatment regimens.
Identifiants
pubmed: 30875421
pii: 5381710
doi: 10.1093/infdis/jiz104
pmc: PMC6581888
doi:
Substances chimiques
Antitubercular Agents
0
Bacterial Proteins
0
Isoniazid
V83O1VOZ8L
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
316-320Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Nat Genet. 2013 Oct;45(10):1176-82
pubmed: 23995134
Am J Respir Crit Care Med. 2017 Nov 1;196(9):1191-1201
pubmed: 28614668
Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1881-4
pubmed: 9620922
J Antimicrob Chemother. 2009 Oct;64(4):786-93
pubmed: 19633001
Lancet Infect Dis. 2018 Sep;18(9):e282-e287
pubmed: 29548923
J Clin Microbiol. 2015 Jun;53(6):1908-14
pubmed: 25854485
Genome Biol. 2014 Mar 03;15(3):R46
pubmed: 24580807
J Clin Microbiol. 2013 Aug;51(8):2633-40
pubmed: 23761144
J Clin Microbiol. 2018 Apr 25;56(5):
pubmed: 29540456
J Antimicrob Chemother. 2013 Dec;68(12):2915-20
pubmed: 23838950
Clin Infect Dis. 2017 Jun 1;64(11):1494-1501
pubmed: 28498943
Eur Respir J. 2017 Dec 28;50(6):
pubmed: 29284687
Genome Med. 2015 May 27;7(1):51
pubmed: 26019726
Thorax. 2019 Mar;74(3):291-297
pubmed: 30420407
Nat Commun. 2015 Dec 21;6:10063
pubmed: 26686880