| Abstract [eng] |
Full title of the thesis: Phenotypic and Molecular Analysis of Cross-Resistance to Second Line Injectible Drugs in Clinical Isolates From Pulmonary Tuberculosis Patients. The aim of the study: To determine the cross-resistance of M. tuberculosis to injectable drugs by phenotypic and PCR methods. Objectives: to evaluate the sensitivity of second line injectables drugs by the phenotypic method; to determine M. tuberculosis resistance to second line antibiotics by PCR method; to evaluate sensitivity and specificity of the PCR method; to compute positive and negative predictive values; to detect gene mutations associated with resistance to second line injectables drugs; to determine and evaluate cross-resistance to injectable by phenotypic and PCR methods. Materials and methods. In this study 78 M. tuberculosis strains, isolated form pulmonary patients, were analysed at Vilnius University Hospital Santaros Klinikos Centre of Laboratory Medicine Tuberculosis Laboratory. Analysis was performed from February 2017 to November 2017. Drug susceptability testing to second line injectible drugs were performed by the phenotypic and PCR methods, the most common genetic mutations, associated with cross-resistace to injectible drugs, were identified. Results and conclusions. PCR analysis showed that resistance to FQ and low-level KAN occurs more frequently than for most anti-tuberculosis drugs. High sensitivity (98%) was determined to fluoroquinolones, higth specificity (94%) was found to amikacin and capreomycin. The most common with fluoroquinolone resistance associated genetic mutation was determined in gyrA gene (D94G), only 9 strains had mutation in rrs gene (A1401G) that associated with cross-resistance mechanism in aminoglycosides, G1484T mutation was not detected. 11 M. tuberculosis strains were characterized by the mutation of the eis gene (C14T), which associated with mono-resistance to kanamycin. Since cross-resistance to injectible drugs was not found in all strains, we propose that clinical isolates should be tested phenotypically to all injectibles. |
