Abstract
Rapid detection of drug resistance in Mycobacterium tuberculosis is important for the successful treatment of tuberculosis. Fluoroquinolone and aminoglycoside resistance detection by molecular methods becomes more complex due to cross resistance among them. Thus, we aimed to determine cross-resistance and mutations in resistance genes for these drugs. A total of 336 multidrug-resistant tuberculosis (MDR-TB) cases received in Mycobacteriology laboratory were screened for phenotypic drug sensitivity testing for second-line drugs, i.e., ofloxacin, amikacin, kanamycin, and capreomycin. Molecular characterization of resistance was done by DNA sequencing of gyrA gene for fuoroquinolones (FQ), and multiplex allele-specific polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) of rrs gene for aminoglycosides. Of 336 MDR-TB isolates, 12 were extensively drug-resistant tuberculosis and 219 were sensitive to all the drugs tested. Ofoxacin, amikacin, kanamycin, and capreomycin resistance was detected in 101 (30.1%), 23 (6.8%), 27 (8.1%), and 19 (5.6%) cases, respectively. Eight different mutations were detected in gyrA gene in ofloxacin-resistant isolates and A1401G nucleotide change in rrs gene were seen in 55.6% (15/27), 65.2% (15/23), and 68.4% (13/29) for kanamycin-, amikacin-, and capreomycin-resistant isolates, respectively. Information on second-line drug resistance-associated mutations could potentially be used for development of newer rapid diagnostic tests.
Highlights
Drug-resistant tuberculosis is a major public health problem in developing countries, which threatens the success of tuberculosis (TB) control programs at the national level
Rapid detection of drug resistance by molecular methods could be of great value in aiding the timely administration of appropriate antibiotics to MDR-TB/XDR-TB patients
Ser91Pro 91 CCG 4 Ser91Pro TCG 91 CCG 9 Wild Type 15 A1401G A1401G 12 Wild Type 15 A1401G A1401G 8 Wild Type 13 A1401G A1401G 6 Wild Type mutations in their targets were characterized in MDR-TB isolates from North India
Summary
Drug-resistant tuberculosis is a major public health problem in developing countries, which threatens the success of tuberculosis (TB) control programs at the national level. An estimated 300,000 pulmonary multidrug-resistant-TB (MDR-TB) patients were notified in 2014, and more than half of these patients were in India, China, and the Russian Federation. The success rate of treatment of MDR-TB is only 50%, largely due to high rates of mortality and loss to follow-up. Among the MDR-TB patients, an estimated 9.7% of people have extensively drug-resistant tuberculosis (XDR-TB) [1]. Rapid detection of MDR- and XDR-TB is necessary for the selection of correct treatment regimen and to reduce the transmission of drug-resistant strains [2]
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