Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates

ABSTRACT Mixed infections and heteroresistance of Mycobacterium tuberculosis contribute to the difficulty of diagnosis, treatment, and control of tuberculosis. However, there is still no proper solution for these issues. This study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors. A total of 499 resistant and susceptible isolates were subjected to spoligotyping and 24-locus variable-number tandem repeat methods to analyze their genotypic lineages and the occurrence of mixed infections. Two hundred ninety-two randomly selected isolates were sequenced on their rpoB gene to examine mutations and heteroresistance. The results showed that 12 patients had mixed infections, and the corresponding isolates belonged to Manu2 ( n = 8), Beijing ( n = 2), T ( n = 1), and unknown ( n = 1) lineages. Manu2 was found to be significantly associated with mixed infections (odds ratio, 47.72; confidence interval, 9.68 to 235.23; P rpoB gene were significantly associated with mixed infections (χ 2 , 56.78; P rpoB gene to become rifampin resistant. Further studies should focus on this lineage to clarify its relevance to mixed infections.