Authors: Brossier, F.¹; Veziris, N.¹; Jarlier, V.¹; Sougakoff, W.²

Source: The International Journal of Tuberculosis and Lung Disease, Volume 13, Number 2, February 2009 , pp. 260-265(6)

Publisher: International Union Against Tuberculosis and Lung Disease

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.

Keywords: tuberculosis; drug resistance; isoniazid; molecular diagnosis; negative predictive value

Document Type: Regular paper

Affiliations: 1: National Reference Centre for Mycobacteria, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France; Université Pierre et Marie Curie (UPMC), Université Paris 06, Faculté de Médecine Pitié-Salpêtrière, Paris, France 2: National Reference Centre for Mycobacteria, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France; Université Pierre et Marie Curie (UPMC), Université Paris 06, Faculté de Médecine Pitié-Salpêtrière, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMRS 872, Equipe 12 Pitié-Salpêtrière), Laboratoire de Recherche Moléculaire sur les Antibiotiques (LRMA), Paris, France

Publication date: 2009-02-01

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• The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

  Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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