Gene mutation and drug resistance of <i>M. tuberculosis</i> in the patients followed up in the city of Moscow

The article describes a retrospective study of the results of microbiological and molecular genetic tests of 685 M. tuberculosis cultures isolated from 685 adult tuberculosis patients registered for dispensary follow-up in Moscow in 2014.The following was identified during the study: phenotypic drug resistance (FDR) of MTB to rifampicin, isoniazid, fluoroquinolones, kanamycin, amikacin, and capreomycin in groups of patients with different treatment history; the frequency of FDR to the above anti-tuberculosis drugs in strains with mutations being drug resistance markers; the frequency of various mutations in case of FDR of mycobacteria in the patients from different groups; the relationship of FDR or the presence of a particular mutation with various characteristics of the patients and their treatment history.The history of previous treatment was determined as statistical significance to provide the greatest influence on the spread of drug resistant MTB: patients undergoing repeated treatment had FDR more often and also a much more pronounced variety of mutations being markers of FDR to certain anti-tuberculosis drugs.The results of the study showed that the detection of genetic mutations in MBT associated with FDR was a reliable tool for predicting phenotypic resistance and should be used as the main method for selecting anti-tuberculosis drugs when compiling the etiotropic therapy regimen

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical <i>Mycobacterium tuberculosis</i> Isolates in Moscow, Russia

<div><p>Background</p><p>The goal of this study was to compare the consistency of three assays for the determination of the drug resistance of <i>Mycobacterium tuberculosis</i> (MTB) strains with various resistance profiles isolated from the Moscow region.</p><p>Methods</p><p>A total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the <i>rpoB</i>, <i>katG</i>, <i>inhA</i>, <i>ahpC</i>, <i>gyrA</i>, <i>gyrB</i>, <i>rrs</i>, <i>eis</i>, and <i>embB</i> genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol.</p><p>Results</p><p>The average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 μg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms.</p><p>Conclusions</p><p>The quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.</p></div

MICs based on the comparison of the MycoTB plate and MGIT 960 results.

<p>MICs based on the comparison of the MycoTB plate and MGIT 960 results.</p

MIC distributions of the clinical isolates characterized using the MGIT and TB-TEST assays.

<p>Resistant and susceptible isolates based on the MGIT results are indicated by the red and green lines, respectively. The light-red and light-green bars represent the numbers of resistant and susceptible isolates with mutations detected by the TB-TEST. The MGIT was not performed for rifabutin (RFB); therefore, only the distributions of all isolates and the isolates with mutations are shown.</p