Thomas C. Victor, Hyeyoung Lee, Sang-Nae Cho, Annemarie M. Jordaan, Gian van der Spuy, Paul D. van Helden, Robin Warren
Molecular Detection of Early Appearance of Drug Resistance during Mycobacterium tuberculosis Infection
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.
Clinical Chemical Laboratory Medicine, Walter de Gruyter
Print ISSN: 1434-6621
Volume: 40, 09/2002
Pages: 876 - 881
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