GenoType MTBDRsl for detection of second-line drugs and ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis isolates at a high-throughput laboratory

Author(s)

Watanabe Pinhata, Juliana Maira ; Brandao, Angela Pires ; Gallo, Juliana Failde ; Siqueira De Oliveira, Ros Angela ; Ferrazoli, Lucilaine

• Document type: Journal article
• Source: DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE; v. 105, n. 2, p. 9-pg., 2023-02-01.

Abstract

We assessed the performance of MTBDRsl for detection of resistance to fluoroquinolones, aminoglycosides/ cyclic peptides, and ethambutol compared to BACTEC MGIT 960 by subjecting simultaneously to both tests 385 phenotypically multidrug-resistant-Mycobacterium tuberculosis isolates from Sao Paulo, Brazil. Discordances were resolved by Sanger sequencing. MTBDRsl correctly detected 99.7% of the multidrug-resistant isolates, 87.8% of the pre-XDR, and 73.9% of the XDR. The assay showed sensitivity of 86.4%, 100%, 85.2% and 76.4% for fluoroquinolones, amikacin/kanamycin, capreomycin and ethambutol, respectively. Specificity was 100% for fluoroquinolones and aminoglycosides/cyclic peptides, and 93.6% for ethambutol. Most fluoroquinolone-discordances were due to mutations in genome regions not targeted by the MTBDRsl v. 1.0: gyrA_H70R and gyrB_R446C, D461N, D449V, and N488D. Capreomycin-resistant isolates with wild-type rrs results on MTBDRsl presented tlyA mutations. MTBDRsl presented good performance for detecting resistance to second-line drugs and ethambutol in clinical isolates. In our setting, multidrug-resistant. isolates presented mutations not targeted by the molecular assay. (c) 2022 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/51756-5 - Performance of methods for diagnosis of multidrug-resistant tuberculosis and Extensively Resistant. Applicability in a Reference Laboratory
• Grantee: Lucilaine Ferrazoli
• Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)
• FAPESP's process: 17/16082-7 - Characterization of mutations in clinical isolates of Mycobacterium tuberculosis resistant to 1st and 2nd line drugs and the relationship between mutations and phenotypic resistance levels to isoniazid.
• Grantee: Rosangela Siqueira de Oliveira
• Support Opportunities: Regular Research Grants