Isoniazid and Rifampin-Resistance Mutations Associated With Resistance to Second-Line Drugs and With Sputum Culture Conversion

Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. In a multicountry prospective cohort study of mul...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	The Journal of infectious diseases Ročník 221; číslo 12; s. 2072
Hlavní autoři:	Click, Eleanor S, Kurbatova, Ekaterina V, Alexander, Heather, Dalton, Tracy L, Chen, Michael P, Posey, James E, Ershova, Julia, Cegielski, J Peter
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 11.06.2020
Témata:	Antitubercular Agents - pharmacology Antitubercular Agents - therapeutic use Bacterial Proteins - genetics Catalase - genetics DNA Mutational Analysis DNA, Bacterial - genetics DNA, Bacterial - isolation & purification DNA-Directed RNA Polymerases - genetics Drug Resistance, Multiple, Bacterial - genetics Genes, Bacterial - genetics Humans Isoniazid - pharmacology Isoniazid - therapeutic use Microbial Sensitivity Tests Mutation Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Oxidoreductases - genetics Promoter Regions, Genetic - genetics Prospective Studies Rifampin - pharmacology Rifampin - therapeutic use Sputum - microbiology Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - microbiology isoniazid drug resistance second-line drugs tuberculosis culture conversion rifampin
ISSN:	1537-6613, 1537-6613
On-line přístup:	Zjistit podrobnosti o přístupu
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. In a multicountry prospective cohort study of multidrug-resistant TB, we identified inhA, katG, and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time to sputum culture conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. In total, 447 participants enrolled from January 2005 to December 2008 from 7 countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance. Relative to mutation of katG only, mutation of inhA promoter and katG was associated with baseline extensively drug resistant (XDR) TB, increased acquired fluoroquinolone resistance, and slower TSCC (125.5 vs 89.0 days). Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1537-6613 1537-6613
DOI:	10.1093/infdis/jiaa042