Risk assessment and transmission of fluoroquinolone resistance in drug-resistant pulmonary tuberculosis: a retrospective genomic epidemiology study

Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDR sl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB...

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Published in:	Scientific reports Vol. 14; no. 1; pp. 19719 - 10
Main Authors:	Nehru, Vijayalakshmi Jawaharlal, Jose Vandakunnel, Maria, Brammacharry, Usharani, Ramachandra, Venkateswari, Pradhabane, Gunavathy, Mani, Balasundaram Revathi, VN, Azger Dusthackeer, Muthaiah, Muthuraj
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 24-08-2024 Nature Publishing Group Nature Portfolio
Subjects:	631/208 631/326 631/337 692/499 692/699 Adult Aged Antitubercular Agents - pharmacology Antitubercular Agents - therapeutic use Codons DNA topoisomerase Drug resistance Drug Resistance, Multiple, Bacterial - genetics Drug-resistant tuberculosis Epidemiology Extensively Drug-Resistant Tuberculosis - drug therapy Extensively Drug-Resistant Tuberculosis - epidemiology Extensively Drug-Resistant Tuberculosis - microbiology Female Fluoroquinolone Fluoroquinolones - pharmacology Fluoroquinolones - therapeutic use Genotypes Humanities and Social Sciences Humans Isoniazid Isoniazid - pharmacology Isoniazid - therapeutic use Kanamycin Male Microbial Sensitivity Tests Middle Aged multidisciplinary Multidrug resistance Mutation Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Retrospective Studies Rifampicin Rifampin Rifampin - pharmacology Rifampin - therapeutic use Risk Assessment RpoB protein Science Science (multidisciplinary) Tuberculosis Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - epidemiology Tuberculosis, Multidrug-Resistant - genetics Tuberculosis, Multidrug-Resistant - microbiology Tuberculosis, Multidrug-Resistant - transmission Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - epidemiology Tuberculosis, Pulmonary - microbiology Drug-resistant tuberculosis Kanamycin Fluoroquinolone Rifampicin Mycobacterium tuberculosis Isoniazid
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Summary:	Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDR sl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34–20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25–3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-70535-y