Prevalence of and molecular basis for tuberculosis drug resistance in the Republic of Georgia: validation of a QIAplex system for detection of drug resistance-related mutations.
We developed a QIAplex system for the simultaneous detection of 24 Mycobacterium tuberculosis gene mutations responsible for resistance to isoniazid (INH), rifampin (RIF), streptomycin (STM), and ethambutol (EMB) in 196 M. tuberculosis isolates recovered in the Republic of Georgia. In comparison to phenotypic susceptibility tests, the QIAplex showed sensitivity and specificity of 85.4% and 96.1% for INH, 94.4% and 99.4% for RIF, 69.6% and 99.2% for STM, 50.0% and 98.8% for EBM, and 86.7% and 100.0% for multidrug resistance, respectively. The dominant resistance mutations revealed were a mutation in katG resulting in S315T (katG S315T), rpsL K43R, and rpoB S531L. Mutations katG S315G and S315T and rpoB S531L were detected with higher frequencies in pretreated patients than in naive patients (P < 0.05). Simultaneous detection of 24 common drug resistance-related mutations provides a molecular tool for studying and monitoring M. tuberculosis resistance mechanism and epidemiology.
Gegia
Medea
M
Georgian Foundation against Tuberculosis and Lung Diseases, National Center of Tuberculosis and Lung Diseases, Tbilisi, Georgia, USA.
Mdivani
Nino
N
Mendes
Rodrigo E
RE
Li
Haijing
H
Akhalaia
Maka
M
Han
Jian
J
Khechinashvili
George
G
Tang
Yi-Wei
YW
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004977:Ethambutol / Q000494:pharmacology; D005846:Georgia (Republic) / Q000453:epidemiology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods*; D015995:Prevalence; D011933:Reagent Kits, Diagnostic; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013307:Streptomycin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011933:Reagent Kits, Diagnostic; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin