AUTHOR=Che Yang , Lin Yi , Yang Tianchi , Chen Tong , Sang Guoxin , Chen Qin , He Tianfeng TITLE=Evaluation of whole-genome sequence to predict drug resistance of nine anti-tuberculosis drugs and characterize resistance genes in clinical rifampicin-resistant Mycobacterium tuberculosis isolates from Ningbo, China JOURNAL=Frontiers in Public Health VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.956171 DOI=10.3389/fpubh.2022.956171 ISSN=2296-2565 ABSTRACT=Setting

Controlling drug-resistant tuberculosis in Ningbo, China.

Objective

Whole-genome sequencing (WGS) has not been employed to comprehensively study Mycobacterium tuberculosis isolates, especially rifampicin-resistant tuberculosis, in Ningbo, China. Here, we aim to characterize genes involved in drug resistance in RR-TB and create a prognostic tool for successfully predicting drug resistance in patients with TB.

Design

Drug resistance was predicted by WGS in a “TB-Profiler” web service after phenotypic drug susceptibility tests (DSTs) against nine anti-TB drugs among 59 clinical isolates. A comparison of consistency, sensitivity, specificity, and positive and negative predictive values between WGS and DST were carried out for each drug.

Results

The sensitivities and specificities for WGS were 95.92 and 90% for isoniazid (INH), 100 and 64.1% for ethambutol (EMB), 97.37 and 100% for streptomycin (SM), 75 and 100% for amikacin (AM), 80 and 96.3%for capreomycin (CAP), 100 and 97.22% for levofloxacin (LFX), 93.33 and 90.91% for prothionamide (PTO), and 70 and 97.96% for para-aminosalicylic acid (PAS). Around 53 (89.83%) and 6 (10.17%) of the isolates belonged to lineage two (East-Asian) and lineage four (Euro-American), respectively.

Conclusion

Whole-genome sequencing is a reliable method for predicting resistance to INH, RIF, EMB, SM, AM, CAP, LFX, PTO, and PAS with high consistency, sensitivity, and specificity. There was no transmission that occurred among the patients with RR-TB in Ningbo, China.