Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial

STREAM Collaborators

Research output: Contribution to journalA1: Web of Science-article

Abstract

OBJECTIVES: To assess the performance of the Geno-Type MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.

METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.

RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/ MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsI-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P <0.001).

CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.

Original languageEnglish
JournalInternational Journal of Tuberculosis and Lung Disease
Volume25
Issue number10
Pages (from-to)839-845
Number of pages7
ISSN1027-3719
DOIs
Publication statusPublished - 2021

Keywords

  • clinical trial
  • fluoroquinolones
  • line-probe assay
  • M. tuberculosis
  • resistant
  • second-line injectables
  • MULTIDRUG-RESISTANT
  • ASSAY
  • TUBERCULOSIS
  • SUSCEPTIBILITY
  • DIAGNOSIS

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