Mixed infections and heteroresistance of Mycobacterium tuberculosis among multidrug-resistant tuberculosis in China: a genomic epidemiology study

Mixed infection refers to the presence of multiple Mycobacterium tuberculosis strains within one host, while heteroresistance denotes the coexistence of drug-susceptible and drug-resistant strains or genotypes. Mixed infections and heteroresistance with Mycobacterium tuberculosis can complicate drug resistance diagnosis, treatment options, and transmission inference. We conducted a population-based genomic epidemiological study of multidrug-resistant tuberculosis (MDR-TB) in Shanghai, China, between January 1, 2005, and December 31, 2018, to evaluate the prevalence and impact of mixed infection and heteroresistance on MDR-TB diagnosis and treatment outcomes. Demographic, clinical, and laboratory data were collected, and factors associated with mixed infections and heteroresistance were identified with multivariable logistic regression analysis. Among the 936 MDR-TB patients in our study, 10.8% (101/936) had mixed infections and 16.5% (154/936) exhibited heteroresistance, which was more frequent with second-line anti-TB drugs (P P