Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Resistance patterns and transmission of mono- and polyresistant TB: clinical impact of WGS

M. Dohál, V. Dvořáková, M. Šperková, M. Pinková, A. Spitaleri, EM. Rasmussen, M. Škereňová, M. Krivošová, E. Gondáš, I. Porvazník, I. Solovič, DM. Cirillo, J. Mokrý

. 2023 ; 5 (5) : dlad108. [pub] 20231004

Status neindexováno Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc23022773

OBJECTIVES: Rapidly diagnosing drug-resistant TB is crucial for improving treatment and transmission control. WGS is becoming increasingly accessible and has added value to the diagnosis and treatment of TB. The aim of the study was to perform WGS to determine the rate of false-positive results of phenotypic drug susceptibility testing (pDST) and characterize the molecular mechanisms of resistance and transmission of mono- and polyresistant Mycobacterium (M.) tuberculosis. METHODS: WGS was performed on 53 monoresistant and 25 polyresistant M. tuberculosis isolates characterized by pDST. Sequencing data were bioinformatically processed to infer mutations encoding resistance and determine the origin of resistance and phylogenetic relationship between isolates studied. RESULTS: The data showed the variable sensitivity and specificity of WGS in comparison with pDST as the gold standard: isoniazid 92.7% and 92.3%; streptomycin 41.9% and 100.0%; pyrazinamide 15% and 94.8%; and ethambutol 75.0% and 98.6%, respectively. We found novel mutations encoding resistance to streptomycin (in gidB) and pyrazinamide (in kefB). Most isolates belonged to lineage 4 (80.1%) and the overall clustering rate was 11.5%. We observed lineage-specific gene variations encoding resistance to streptomycin and pyrazinamide. CONCLUSIONS: This study highlights the clinical potential of WGS in ruling out false-positive drug resistance following phenotypic or genetic drug testing, and recommend this technology together with the WHO catalogue in designing an optimal individualized treatment regimen and preventing the development of MDR TB. Our results suggest that resistance is primarily developed through spontaneous mutations or selective pressure.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23022773
003      
CZ-PrNML
005      
20240522093153.0
007      
ta
008      
240105s2023 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/jacamr/dlad108 $2 doi
035    __
$a (PubMed)37799267
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Dohál, Matúš $u Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia $7 xx0317390
245    10
$a Resistance patterns and transmission of mono- and polyresistant TB: clinical impact of WGS / $c M. Dohál, V. Dvořáková, M. Šperková, M. Pinková, A. Spitaleri, EM. Rasmussen, M. Škereňová, M. Krivošová, E. Gondáš, I. Porvazník, I. Solovič, DM. Cirillo, J. Mokrý
520    9_
$a OBJECTIVES: Rapidly diagnosing drug-resistant TB is crucial for improving treatment and transmission control. WGS is becoming increasingly accessible and has added value to the diagnosis and treatment of TB. The aim of the study was to perform WGS to determine the rate of false-positive results of phenotypic drug susceptibility testing (pDST) and characterize the molecular mechanisms of resistance and transmission of mono- and polyresistant Mycobacterium (M.) tuberculosis. METHODS: WGS was performed on 53 monoresistant and 25 polyresistant M. tuberculosis isolates characterized by pDST. Sequencing data were bioinformatically processed to infer mutations encoding resistance and determine the origin of resistance and phylogenetic relationship between isolates studied. RESULTS: The data showed the variable sensitivity and specificity of WGS in comparison with pDST as the gold standard: isoniazid 92.7% and 92.3%; streptomycin 41.9% and 100.0%; pyrazinamide 15% and 94.8%; and ethambutol 75.0% and 98.6%, respectively. We found novel mutations encoding resistance to streptomycin (in gidB) and pyrazinamide (in kefB). Most isolates belonged to lineage 4 (80.1%) and the overall clustering rate was 11.5%. We observed lineage-specific gene variations encoding resistance to streptomycin and pyrazinamide. CONCLUSIONS: This study highlights the clinical potential of WGS in ruling out false-positive drug resistance following phenotypic or genetic drug testing, and recommend this technology together with the WHO catalogue in designing an optimal individualized treatment regimen and preventing the development of MDR TB. Our results suggest that resistance is primarily developed through spontaneous mutations or selective pressure.
590    __
$a NEINDEXOVÁNO
655    _2
$a časopisecké články $7 D016428
700    1_
$a Dvořáková, Věra $u National Reference Laboratory for Mycobacteria, National Institute of Public Health, Prague, Czech Republic
700    1_
$a Šperková, Miluše $u National Reference Laboratory for Mycobacteria, National Institute of Public Health, Prague, Czech Republic
700    1_
$a Pinková, Martina $u National Reference Laboratory for Mycobacteria, National Institute of Public Health, Prague, Czech Republic
700    1_
$a Spitaleri, Andrea $u Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy $u Vita-Salute San Raffaele University, Milan, Italy
700    1_
$a Rasmussen, Erik Michael $u International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark
700    1_
$a Škereňová, Mária $u Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia $u Department of Molecular Medicine, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia
700    1_
$a Krivošová, Michaela $u Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia
700    1_
$a Gondáš, Eduard $u Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia
700    1_
$a Porvazník, Igor $u Department of Clinical Microbiology and Department of Pneumophthiology, National Institute of Tuberculosis, Lung Diseases and Thoracic Surgery, Vyšné Hágy, Slovakia $u Faculty of Health, Catholic University, Ružomberok, Slovakia
700    1_
$a Solovič, Ivan $u Department of Clinical Microbiology and Department of Pneumophthiology, National Institute of Tuberculosis, Lung Diseases and Thoracic Surgery, Vyšné Hágy, Slovakia
700    1_
$a Cirillo, Daniela Maria $u Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
700    1_
$a Mokrý, Juraj $u Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia
773    0_
$w MED00214252 $t JAC-antimicrobial resistance $x 2632-1823 $g Roč. 5, č. 5 (2023), s. dlad108
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37799267 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240105 $b ABA008
991    __
$a 20240522093149 $b ABA008
999    __
$a ok $b bmc $g 2036385 $s 1209218
BAS    __
$a 3
BAS    __
$a PreBMC-PubMed-not-MEDLINE
BMC    __
$a 2023 $b 5 $c 5 $d dlad108 $e 20231004 $i 2632-1823 $m JAC-antimicrobial resistance $n JAC Antimicrob Resist $x MED00214252
LZP    __
$a Pubmed-20240105

Najít záznam

Citační ukazatele

Možnosti archivace