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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

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Molecular Detection of Early Appearance of Drug Resistance during Mycobacterium tuberculosis Infection

Thomas C. Victor / Hyeyoung Lee / Sang-Nae Cho / Annemarie M. Jordaan / Gian van der Spuy / Paul D. van Helden / Robin Warren

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 40, Issue 9, Pages 876–881, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2002.155, June 2005

Publication History

Published Online:
2005-06-01

Abstract

During the early development of drug resistance in Mycobacterium tuberculosis (M. tuberculosis) infection only a small proportion of resistant bacteria are present within a milieu of sensitive bacteria. This complicates the use of molecular methods to predict the presence of a resistant phenotype and has been largely ignored in many of the newly developed molecular methods. In this study, mixtures of DNA from M. tuberculosis strains with known wild-type and mutant sequences were used to evaluate the sensitivity of three different molecular methods for detection of drug resistance. The dot-blot and amplification refractory mutation system (ARMS) methods showed sensitivities that approach those of routine phenotypic methods and are able to detect the presence of mutant sequences at a ratio of 1 in 50 (corresponding to 2% mutant sequences). This is 10-fold more sensitive than the commercial kit. The ARMS method was also used to investigate the use of molecular methods to identify mixed infections, and both drug-resistant and susceptible strain populations were identified in a single clinical isolate. These findings highlight the applicability of molecular methods to the rapid detection of drug resistance in tuberculosis patients, particularly in those who are non-compliant and in contacts of known drug-resistant tuberculosis patients, and assistance in limiting the spread of drug-resistant strains.

Citing Articles

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[1]
Igor Mokrousov, N.Vijaya Bhanu, Philip N Suffys, Gururaj V Kadival, Sook-Fan Yap, Sang-Nae Cho, Annemarie M Jordaan, Olga Narvskaya, Urvashi B Singh, Harrison M Gomes, Hyeyoung Lee, Savita P Kulkarni, Kuo-Chieh Lim, Baldip K Khan, Dick van Soolingen, Thomas C Victor, and Leo M Schouls
Journal of Microbiological Methods, 2004, Volume 57, Number 3, Page 323
[2]
Sang-Nae Cho and Patrick J. Brennan
Tuberculosis, 2007, Volume 87, Page S14
[3]
Paul D van Helden, Peter R Donald, Thomas C Victor, H Simon Schaaf, Eileen G Hoal, Gerhard Walzl, and Robin M Warren
Expert Review of Anti-infective Therapy, 2006, Volume 4, Number 5, Page 759

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