Abstract

BACKGROUND: Whole genome sequencing (WGS) is rarely used for drug-resistance testing of Mycobacterium tuberculosis in high-endemic settings. We present the first study from Indonesia, which has the second highest tuberculosis (TB) burden worldwide, with less than 50% of drug-resistant cases currently detected.

METHODS: We applied WGS in strains from 322 adult HIV-negative TB patients. Phenotypic DST was done for a portion of patients.

RESULTS: Fifty-one isolates (15.8%) harboured drug resistance mutations, including 42 among 322 patients (13.0%) with no prior TB treatment. Eight (2.5%) isolates were multidrug-resistant (MDR), 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). The agreement of WGS-based resistance and phenotypic drug susceptibility testing (DST) to first-line drugs was high for isoniazid, rifampicin, and streptomycin, and less for ethambutol. Drug resistance was more common in Indo-Oceanic lineage strains (37.5%) than Euro-American (18.2%) and East-Asian lineage strains (10.3%; p=0.044), but combinations of multiple mutations were most common among East-Asian lineage strains (p=0.054).

CONCLUSIONS: Our data support the potential use of WGS for more rapid and comprehensive prediction ofDR-TB in Indonesia. Future studies should address potential barriers in implementing WGS, the distribution of specific resistance mutations, and associations of particular mutations with endemic M. tuberculosis lineages in Indonesia.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalJournal of Global Antimicrobial Resistance
Volume16
DOIs
Publication statusPublished - Mar 2019
Externally publishedYes

Keywords

  • Mycobacterium tuberculosis
  • drug resistance
  • whole genome sequencing
  • resistance mutations

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