Disputed <em>rpoB</em> mutations in <em>Mycobacterium tuberculosis</em> and tuberculosis treatment outcomes

Antimicrob Agents Chemother. 2021 Apr 12:AAC.01573-20. doi: 10.1128/AAC.01573-20. Online ahead of print.


Discordant results for Mycobacterium tuberculosis isolates with disputed mutations between genotypic drug susceptibility testing (DST) (gDST) and phenotypic DST (pDST) impact RIF-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) treatments due to a lack of practical clinical guidelines. To investigate the role of disputed rpoB mutations in M. tuberculosis and TB treatment outcomes, initial isolates of 837 clinical RR or MDR-TB cases confirmed during 2014-2018 were retested using agar-based RIF pDST and rpoB gene sequencing. Minimum inhibitory concentrations (MICs) were determined for isolates with disputed rpoB mutations. Disputed rpoB mutations were identified in 77 (9.2%) M. tuberculosis isolates, including 50 (64.9%) and 14 (18.2%) phenotypic RIF- and rifabutin (RFB)-resistant isolates, respectively. The predominant single mutations were L533P (44.2%) and L511P (20.8%). Most of the isolates harboring L511P (87.5%), H526N (100%), D516Y (70.0%) and L533P (63.6%) mutations had MICs ≤1 mg/L, whereas isolates harboring H526L (75%) had MICs > 1 mg/L. Of the 63 cases with treatment outcomes, 11 (17.5%) cases died, 1 (1.6%) case transferred out and 51 (81%) cases had favorable outcomes, including 8 and 20 cases treated with standard-dose RIF- and RFB-containing regimens, respectively. Excluding cases transferred out, received no or 1-day treatment, we observed statistically significant differences between active and inactive fluoroquinolones (FQs) [P =0.004, Odds ratio =0.05 (95% confidence intervals, 0.01-0.38)] in 57 cases. We concluded that disputed rpoB mutations are not rare. Depending on resources, sequencing and/or MIC testing is recommended for better management of RR and MDR-TB cases.

PMID:33846134 | DOI:10.1128/AAC.01573-20