Drug-resistant Mycobacterium tuberculosis among Nepalese patients at a tuberculosis referral center

• Published in: PloS one 2024-05, Vol.19 (5), p.e0301210-e0301210
• Main Authors: Chand, Arun Bahadur, Basnet, Ajaya, Maharjan, Bhagwan, Rai, Ganesh, Joshi, Yadav Prasad, Bhatt, Lok Raj, Sen, Bindu, Rai, Shiba Kumar
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age groups; Aged; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Biology and Life Sciences; Codon; Codons; Cross-Sectional Studies; Data analysis; DNA topoisomerase; Drug resistance; Drug resistance in microorganisms; Drug Resistance, Multiple, Bacterial - genetics; Drug therapy; Extensively Drug-Resistant Tuberculosis - drug therapy; Extensively Drug-Resistant Tuberculosis - epidemiology; Extensively Drug-Resistant Tuberculosis - microbiology; Female; Females; Fluoroquinolones - pharmacology; Fluoroquinolones - therapeutic use; Gene mutations; Genes; Genetic testing; Genotypes; Humans; Information management; Isoniazid; Isoniazid - pharmacology; Isoniazid - therapeutic use; Kanamycin; Laboratories; Male; Males; Medical diagnosis; Medical research; Medicine and Health Sciences; Medicine, Experimental; Microbial Sensitivity Tests; Middle Aged; Multidrug resistance; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Nepal - epidemiology; Patients; People and Places; Peptides; Rifampin; Rifampin - pharmacology; Rifampin - therapeutic use; Rrs gene; Sociodemographics; Statistics; Strains (organisms); Tuberculosis; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - epidemiology; Tuberculosis, Multidrug-Resistant - microbiology; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0301210

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