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Background  Multidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in  Mycobacterium tuberculosis  isolates from a national reference center.    Methods and Findings  Ninety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the  rpoB  and  katG  genes were screened for mutations. Genotypic diversity was investigated by  IS6110 -RFLP and Luminex 47 spoligotyping. Mutations in  rpoB  and  katG  were seen in 91% and 93% of the isolates, respectively. Codon 315  katG  mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical  IS6110 -RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516  rpoB  mutations while codon 531 mutations prevailed in the other isolates.    Conclusions  Our data suggest that there were no major multidrug resistant  M. tuberculosis  strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.

Multidrug Resistant Mycobacterium tuberculosis: A Retrospective katG and rpoB Mutation Profile Analysis in Isolates from a Reference Center in Brazil