Performance of MTBDR plus for detecting high/low levels of Mycobacterium tuberculosis resistance to isoniazid

Int J Tuberc Lung Dis. 2009 Feb;13(2):260-5.

Abstract

Setting: We recently evaluated the Genotype MTBDR test for assessing Mycobacterium tuberculosis resistance to rifampicin (RMP) and isoniazid (INH) by detecting mutations in rpoB (codons 511-533) and katG (codon 315). A new version of the test, MTBDR plus, has been designed to also detect mutations in the regulatory region of inhA.

Objective: To evaluate the performance of MTBDR plus over MTBDR.

Results: In 113 isolates, MTBDR plus detected all 76 RMP-resistant (RMP-R) strains and all 64 INH-resistant (INH-R) strains with KatG-315 mutations, 59 of which displayed a high level of INH resistance. It also identified 18 strains undetectable by MTBDR, without mutation in KatG-315 but with a -15 C-->T mutation in the regulatory region of inhA, of which 15 displayed a low level of INH resistance. Thirteen INH-R strains, which mainly harboured mutations in KatG at positions other than 315, were undetected by MTBDR plus.

Conclusion: MTBDR plus retains the accuracy shown by MTBDR in detecting RMP resistance and is more sensitive in detecting INH resistance (86% vs. 67%), particularly at low levels (minimum inhibitory concentration<1 mg/l, 69% vs. 17%). The negative predictive value of the test (the probability of a strain with a wild-type test being susceptible to INH) is >98% when the rate of INH is <10%, as it is in France.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Biological Assay / methods*
  • Biological Assay / statistics & numerical data
  • DNA-Directed RNA Polymerases
  • Drug Resistance, Bacterial / genetics*
  • Humans
  • Isoniazid / pharmacology*
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Predictive Value of Tests
  • Reproducibility of Results
  • Rifampin / pharmacology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • rpoB protein, Mycobacterium tuberculosis
  • DNA-Directed RNA Polymerases
  • Isoniazid
  • Rifampin