Use of whole-genome sequencing to predict Mycobacterium tuberculosis drug resistance in Indonesia

Journal of Global Antimicrobial Resistance
Lidya ChaidirBachti Alisjahbana

Abstract

Whole-genome sequencing (WGS) is rarely used for drug resistance testing of Mycobacterium tuberculosis in high-endemic settings. Here we present the first study from Indonesia, which has the third highest tuberculosis (TB) burden worldwide, with <50% of drug-resistant cases currently detected. WGS was applied for strains from 322 human immunodeficiency virus (HIV)-negative adult TB patients. Phenotypic drug susceptibility testing (DST) was performed for a proportion of the patients. Using WGS, mutations associated with drug resistance to any TB drug were identified in 51 (15.8%) of the 322 patients, including 42 patients (13.0%) with no prior TB treatment (primary resistance). Eight isolates (2.5%) were multidrug-resistant (MDR) and one was extensively drug-resistant (XDR). Most mutations were found in katG (n=18), pncA (n=18), rpoB (n=10), fabG1 (n=9) and embB (n=9). Agreement of WGS-based resistance and phenotypic DST to first-line drugs was high for isoniazid and rifampicin but was lower for ethambutol and streptomycin. Drug resistance was more common in Indo-Oceanic lineage strains (37.5%) compared with Euro-American (18.2%) and East-Asian lineage strains (10.3%) (P=0.044), but combinations of multiple mutations were most c...Continue Reading

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