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[Extensive genetic analysis of clinical tuberculosis isolates and analysis of host factors to evaluate rapid development of multidrug resistance during initial treatment].

INTRODUCTION
In this study, we aimed at determining the cause of resistance to tuberculosis treatment by performing genetic analyses of bacteria obtained from a patient who developed multidrug-resistant tuberculosis (MDR-TB) during the initial course of treatment for tuberculosis.


METHODS
Specimens obtained before and after the development of MDR-TB were subjected to spoligotyping, drug-resistance gene analysis, and variable-number tandem repeat (VNTR) typing. The patient's clinical background was also reviewed.


RESULTS
After the development of resistance, the bacterial genome had changed with regard to only 1 mutation: S531L in the rpoB gene. Spoligotyping revealed that the genotype was that of the Beijing strain. VNTR typing confirmed all 35 loci. Review of the patient's clinical background showed that diabetes mellitus was present as a complication.


DISCUSSION
There was no evidence of reinfection or polyclonal infection. The strain belonged to a sublineage of the Beijing genotype that is a common precipitating cause of MDR-TB due to this genotype. The patient had diabetes mellitus and was thus vulnerable to the development of resistance. Factors associated with both the host and bacteria, therefore, contributed to the development of resistance in this case, which seemed to result in the rapid development of MDR-TB.