Abstract
Molecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013–2019 versus 2006–2012. Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.
Highlights
IntroductionAn estimated 465,000 people developed TB that was resistant to rifampin (RR-TB), and of these, nearly 363,000 (78%) were multidrug-resistant (MDR)-TB (defined as infection with Mycobacterium tuberculosis strain resistant at least to rifampin, RIF and isoniazid, INH; the two most effective first-line drugs) c ases[1]
6.2% of all MDR-TB cases have XDR-TB [MDR-TB strains resistant to a fluoroquinolone (FQ) plus a second-line injectable drug (SLID); kanamycin (KAN), amikacin (AMI) or capreomycin (CAP)] and at least case of XDR-TB has been reported by 131 countries/territories by the end of 20186
50 pansusceptible M. tuberculosis isolates cultured from 34 respiratory and 16 non-respiratory samples collected from 50 patients were used (Table 1)
Summary
An estimated 465,000 people developed TB that was resistant to rifampin (RR-TB), and of these, nearly 363,000 (78%) were multidrug-resistant (MDR)-TB (defined as infection with Mycobacterium tuberculosis strain resistant at least to rifampin, RIF and isoniazid, INH; the two most effective first-line drugs) c ases[1]. The WHO has further categorized infection with M. tuberculosis strains resistant only to RIF and INH without additional resistance to other first-line (ethambutol, EMB and pyrazinamide, PZA) drugs as uncomplicated MDR-TB. 6.2% of all MDR-TB cases have XDR-TB [MDR-TB strains resistant to a fluoroquinolone (FQ) plus a second-line injectable drug (SLID); kanamycin (KAN), amikacin (AMI) or capreomycin (CAP)] and at least case of XDR-TB has been reported by 131 countries/territories by the end of 20186. Detection of M. tuberculosis in clinical specimens, its susceptibility to anti-TB drugs, and effective treatment are essential for global TB control e fforts[3,4,5,6,7]
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