A Comparison of Phenotypic and WGS Drug Susceptibility Testing in Isolates from the Republic of Korea

Overview

Journal JAC Antimicrob Resist

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2023 May 16

PMID 37193005

Authors

Seung Heon Lee

Elena Ferran

Adam A Witney

Sungweon Ryu

Hyungseok Kang

Nathaniel Storey

Timothy D McHugh

Giovanni Satta

Affiliations

Soon will be listed here.

Abstract

Background: WGS has significant potential to help tackle the major public health problem of TB. The Republic of Korea has the third highest rates of TB of all Organisation for Economic Cooperation and Development countries but there has been very limited use of WGS in TB to date.

Objectives: A retrospective comparison of (MTB) clinical isolates from 2015 to 2017 from two centres in the Republic of Korea using WGS to compare phenotypic drug susceptibility testing (pDST) and WGS drug susceptibility predictions (WGS-DSP).

Methods: Fifty-seven MTB isolates had DNA extracted and were sequenced using the Illumina HiSeq platform. The WGS analysis was performed using bwa mem, bcftools and IQ-Tree; resistance markers were identified using TB profiler. Phenotypic susceptibilities were carried out at the Supranational TB reference laboratory (Korean Institute of Tuberculosis).

Results: For first-line antituberculous drugs concordance for rifampicin, isoniazid, pyrazinamide and ethambutol was 98.25%, 92.98%, 87.72% and 85.96%, respectively. The sensitivity of WGS-DSP compared with pDST for rifampicin, isoniazid, pyrazinamide and ethambutol was 97.30%, 92.11%, 78.95% and 95.65%, respectively. The specificity for these first-line antituberculous drugs was 100%, 94.74%, 92.11% and 79.41%, respectively. The sensitivity and specificity for second-line drugs ranged from 66.67% to 100%, and from 82.98% to 100%, respectively.

Conclusions: This study confirms the potential role for WGS in drug susceptibility prediction, which would reduce turnaround times. However, further larger studies are needed to ensure current databases of drug resistance mutations are reflective of the TB present in the Republic of Korea.

References

Enkirch T, Werngren J, Groenheit R, Alm E, Advani R, Karlberg M . Systematic Review of Whole-Genome Sequencing Data To Predict Phenotypic Drug Resistance and Susceptibility in Swedish Mycobacterium tuberculosis Isolates, 2016 to 2018. Antimicrob Agents Chemother. 2020; 64(5). PMC: 7179598. DOI: 10.1128/AAC.02550-19. View

van der Werf M, Kodmon C . Whole-Genome Sequencing as Tool for Investigating International Tuberculosis Outbreaks: A Systematic Review. Front Public Health. 2019; 7:87. PMC: 6478655. DOI: 10.3389/fpubh.2019.00087. View

Lee M, Han J, Kim Y, Kwak N, Kim J, Park O . Multidrug-resistant tuberculosis in South Korea: a retrospective analysis of national registry data in 2011-2015. Int J Tuberc Lung Dis. 2019; 23(7):850-857. DOI: 10.5588/ijtld.18.0658. View

Iwamoto T, Murase Y, Yoshida S, Aono A, Kuroda M, Sekizuka T . Overcoming the pitfalls of automatic interpretation of whole genome sequencing data by online tools for the prediction of pyrazinamide resistance in Mycobacterium tuberculosis. PLoS One. 2019; 14(2):e0212798. PMC: 6394917. DOI: 10.1371/journal.pone.0212798. View

Walker T, Kohl T, Omar S, Hedge J, Del Ojo Elias C, Bradley P . Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis. 2015; 15(10):1193-1202. PMC: 4579482. DOI: 10.1016/S1473-3099(15)00062-6. View

Cho E, Bae H, Kang S, Lee E . Detection of isoniazid and rifampicin resistance by sequencing of katG, inhA, and rpoB genes in Korea. Korean J Lab Med. 2009; 29(5):455-60. DOI: 10.3343/kjlm.2009.29.5.455. View

Witney A, Gould K, Arnold A, Coleman D, Delgado R, Dhillon J . Clinical application of whole-genome sequencing to inform treatment for multidrug-resistant tuberculosis cases. J Clin Microbiol. 2015; 53(5):1473-83. PMC: 4400773. DOI: 10.1128/JCM.02993-14. View

Allix-Beguec C, Arandjelovic I, Bi L, Beckert P, Bonnet M, Bradley P . Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. N Engl J Med. 2018; 379(15):1403-1415. PMC: 6121966. DOI: 10.1056/NEJMoa1800474. View

Wu X, Gao R, Shen X, Guo Y, Yang J, Wu Z . Use of whole-genome sequencing to predict Mycobacterium tuberculosis drug resistance in Shanghai, China. Int J Infect Dis. 2020; 96:48-53. DOI: 10.1016/j.ijid.2020.04.039. View

10.

Kim S . Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J. 2005; 25(3):564-9. DOI: 10.1183/09031936.05.00111304. View

11.

Han S, Song T, Cho Y, Kim J, Choi S, Bang H . Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family. Stand Genomic Sci. 2015; 10:78. PMC: 4606834. DOI: 10.1186/s40793-015-0071-4. View

12.

Papaventsis D, Casali N, Kontsevaya I, Drobniewski F, Cirillo D, Nikolayevskyy V . Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review. Clin Microbiol Infect. 2016; 23(2):61-68. DOI: 10.1016/j.cmi.2016.09.008. View

13.

Bouzouita I, Cabibbe A, Trovato A, Draoui H, Ghariani A, Midouni B . Is sequencing better than phenotypic tests for the detection of pyrazinamide resistance?. Int J Tuberc Lung Dis. 2018; 22(6):661-666. DOI: 10.5588/ijtld.17.0715. View

14.

Heyckendorf J, Andres S, Koser C, Olaru I, Schon T, Sturegard E . What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi- and Extensively Drug-Resistant Tuberculosis. Antimicrob Agents Chemother. 2017; 62(2). PMC: 5786814. DOI: 10.1128/AAC.01550-17. View

15.

Walker T, Merker M, Kohl T, Crook D, Niemann S, Peto T . Whole genome sequencing for M/XDR tuberculosis surveillance and for resistance testing. Clin Microbiol Infect. 2016; 23(3):161-166. DOI: 10.1016/j.cmi.2016.10.014. View

16.

Bateson A, Canseco J, McHugh T, Witney A, Feuerriegel S, Merker M . Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid. J Antimicrob Chemother. 2022; 77(6):1685-1693. PMC: 9155602. DOI: 10.1093/jac/dkac070. View

17.

Ryoo S, Lee J, Oh J, Kim B, Kim Y, Kim J . Comparing Two Mycobacterium tuberculosis Genomes from Chinese Immigrants with Native Genomes Using Mauve Alignments. Tuberc Respir Dis (Seoul). 2018; 81(3):216-221. PMC: 6030666. DOI: 10.4046/trd.2017.0091. View

18.

Ramachandran G, Swaminathan S . Safety and tolerability profile of second-line anti-tuberculosis medications. Drug Saf. 2015; 38(3):253-69. DOI: 10.1007/s40264-015-0267-y. View

19.

Ali A, Hasan Z, McNerney R, Mallard K, Hill-Cawthorne G, Coll F . Whole genome sequencing based characterization of extensively drug-resistant Mycobacterium tuberculosis isolates from Pakistan. PLoS One. 2015; 10(2):e0117771. PMC: 4342168. DOI: 10.1371/journal.pone.0117771. View

20.

Walker T, Ip C, Harrell R, Evans J, Kapatai G, Dedicoat M . Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis. 2012; 13(2):137-46. PMC: 3556524. DOI: 10.1016/S1473-3099(12)70277-3. View