» Articles » PMID: 38709710

Drug-resistant Mycobacterium Tuberculosis Among Nepalese Patients at a Tuberculosis Referral Center

Overview
Journal PLoS One
Date 2024 May 6
PMID 38709710
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Multidrug-resistant tuberculosis (MDR-TB), characterized by isoniazid and rifampicin resistance, is caused by chromosomal mutations that restrict treatment options and complicate tuberculosis management. This study sought to investigate the prevalence of pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) tuberculosis, as well as mutation pattern, in Nepalese patients with MDR/rifampicin-resistant (RR)-TB strains.

Methods: A cross-sectional study was conducted on MDR/RR-TB patients at the German Nepal Tuberculosis Project from June 2017 to June 2018. The MTBDRsl line probe assay identified pre-XDR-TB and XDR-TB. Pre-XDR-TB included MDR/RR-TB with resistance to any fluoroquinolone (FLQ), while XDR-TB included MDR/RR-TB with resistance to any FLQ and at least one additional group A drug. Mutation status was determined by comparing bands on reaction zones [gyrA and gyrB for FLQ resistance, rrs for SILD resistance, and eis for low-level kanamycin resistance, according to the GenoType MTBDRsl VER 2.0, Hain Lifescience GmbH, Nehren, Germany definition of pre-XDR and XDR] to the evaluation sheet. SPSS version 17.0 was used for data analysis.

Results: Out of a total of 171 patients with MDR/RR-TB, 160 had (93.57%) had MTBC, of whom 57 (35.63%) had pre-XDR-TB and 10 (6.25%) had XDR-TB. Among the pre-XDR-TB strains, 56 (98.25%) were FLQ resistant, while 1 (1.75%) was SLID resistant. The most frequent mutations were found at codons MUT3C (57.14%, 32/56) and MUT1 (23.21%, 13/56) of the gyrA gene. One patient had SLID resistant genotype at the MUT1 codon of the rrs gene (100%, 1/1). XDR-TB mutation bands were mostly detected on MUT1 (30%, 3/10) of the gyrA and rrs, MUT3C (30%, 3/10) of the gyrA, and MUT1 (30%, 3/10) of the rrs.

Conclusions: Pre-XDR-TB had a significantly higher likelihood than XDR-TB, with different specific mutation bands present in gyrA and rrs genes.

References
1.
Dalton T, Cegielski P, Akksilp S, Asencios L, Caoili J, Cho S . Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study. Lancet. 2012; 380(9851):1406-17. PMC: 11019390. DOI: 10.1016/S0140-6736(12)60734-X. View

2.
Conkle-Gutierrez D, Kim C, Ramirez-Busby S, Modlin S, Mansjo M, Werngren J . Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study. Antimicrob Agents Chemother. 2022; 66(6):e0207521. PMC: 9211393. DOI: 10.1128/aac.02075-21. View

3.
Che Y, Song Q, Yang T, Ping G, Yu M . Fluoroquinolone resistance in multidrug-resistant independent of fluoroquinolone use. Eur Respir J. 2017; 50(6). DOI: 10.1183/13993003.01633-2017. View

4.
Yuan X, Zhang T, Kawakami K, Zhu J, Li H, Lei J . Molecular characterization of multidrug- and extensively drug-resistant Mycobacterium tuberculosis strains in Jiangxi, China. J Clin Microbiol. 2012; 50(7):2404-13. PMC: 3405621. DOI: 10.1128/JCM.06860-11. View

5.
Chen Y, Yuan Z, Shen X, Wu J, Wu Z, Xu B . Resistance to Second-Line Antituberculosis Drugs and Delay in Drug Susceptibility Testing among Multidrug-Resistant Tuberculosis Patients in Shanghai. Biomed Res Int. 2016; 2016:2628913. PMC: 5019859. DOI: 10.1155/2016/2628913. View