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J Glob Antimicrob Resist. 2018 Aug 29. pii: S2213-7165(18)30165-6. doi: 10.1016/j.jgar.2018.08.018. [Epub ahead of print]

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

Author information

1
Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Eijkman 38, Bandung, 40161, Indonesia. Electronic address: lidya.chaidir@unpad.ac.id.
2
Department of Medicine, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Nijmegen, 6525 GA, The Netherlands.
3
Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Geert Groteplein 8, Nijmegen, 6500 HB, The Netherlands.
4
Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Eijkman 38, Bandung, 40161, Indonesia; Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Pasir Kaliki 38, Bandung, 40161, Indonesia.
5
West Java Provincial Referral Laboratory, Sederhana 3-5, Bandung, 40161, Indonesia.
6
Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Eijkman 38, Bandung, 40161, Indonesia.
7
Centre for International Health, Dunedin School of Medicine, University of Otago, PO Box 5 Box 56, Dunedin, 9054, New Zealand.

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.

KEYWORDS:

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

PMID:
30172045
DOI:
10.1016/j.jgar.2018.08.018

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