ABSTRACT
Resistances to anti-tuberculosis (TB) drugs are related to the mutations in the genome of the Mycobacterium tuberculosis complex (MTBC). To expose the genomic mutations that cause anti-TB drug resistance. The GenoType MTBDRplus and MTBDRsl assays were used to detect genetic mutations. In this study of 1329 MTBC isolates, the sensitivities and specificities of genotypic methods for the detection of isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and multi-drug resistance were 0.77, 0.84, 0.65, 0.89 and 0.99, 0.98, 0.67, 0.94, respectively. MUT3 mutations (S531L) of the rpoB gene for RIF resistance and MUT1 mutations (S315T1 and C15T) of the katG and inhA genes for INH resistance were dominant. The most frequently observed mutations that created resistance to fluoroquinolones (FLQ) were MUT3C (D94G) of the gyrA gene. The predominant mutations of EMB resistance were MUT1B (M306V) of the embB gene. Aminoglycosides/cyclic peptides (AG/CP) resistance was rare. The molecular mechanisms of anti-TB drugs resistance in MTBC strains found in Istanbul are similar to those in the literature.
Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/genetics , Adult , Aminoglycosides/pharmacology , Ethambutol/pharmacology , Female , Fluoroquinolones/pharmacology , Genotype , Humans , Isoniazid/pharmacology , Male , Microbial Sensitivity Tests , Middle Aged , Phenotype , Rifampin/pharmacology , Turkey/epidemiologyABSTRACT
INTRODUCTION: Tuberculosis (TB) is continuing to be a important public health problem in the undeveloped countries. Drug sensitivity rate should be monitored for the effective treatment and control in the TB. The aim of this study was to determine the rate of resistance to first line TB drugs in the Mycobacterium tuberculosis complex isolates. MATERIALS AND METHODS: During one-year period, M. tuberculosis complex was isolated in the 1193 samples from 974 patients in the Mycobacterial Laboratory of Yedikule Chest Diseases and Chest Surgery Education and Research Hospital, Istanbul, Turkey. The majority of samples isolated in the M. tuberculosis complex were sputum (n= 897, 92.1%). Anti-TB drug susceptibility testing was performed with Mycobacterium Growth Indicator Tube 960 system. RESULT: Two hundred and sixty isolat (26.7%) were resistant to at least one of the four first-line anti-TB drugs tested. One hundred ninety seven isolates were resistances to isoniazid (20.2%); 82 to rifampin (8.4%), 63 to ethambutol (6.5%) and 140 to streptomycin (14.4%). Of the 197 isoniazid-resistant isolates, 89 (45.2%) isolates was only isoniazid-resistance, only rifampin-resistance were found 15.9% (n= 13), ethambutol 7.9% (n= 5) and streptomycin 30.7% (n= 43). There were 48 (4.9%) isolates with two drugresistance, 22 (2.3%) isolates with three drug-resistance, and 42 (4.3%) isolates with four drug-resistance. The multidrug resistance rate was 7% (68 of 974). There was no relationship with between the frequency of TB drug resistance and gender or age. The isoniazid--resistance and streptomycin-resistance were seen to tend to increase if together considered the results of this study with outcomes of previously reported studies from Turkey in the 1998-2003, 2004-2007 and 2008-2010 years. CONCLUSIONS: Monitoring of drug susceptibility test results can contribute to the management of TB treatment and increase treatment success. Isoniazid-resistance and streptomycin-resistance tend to increase in Turkey. Further clinical studies are needed to investigate regional and global factors affecting the development of resistance to first-line TB drugs.
