Clinical and epidemiologic implications of polyclonal infection due to Mycobacterium avium complex

Molecular typing techniques have confirmed that most monomicrobial bacterial infections (e.g. infections due to Escherichia coli, Hemophilus influenzae, Salmonella spp.) represent monoclonal infections. That is, the infecting bacterial population is derived from the clonal expansion of a single organism. During the course of infection and treatment, the combination of random mutations and selective pressure may result in subpopulations of organisms with altered phenotypic characteristics such as antimicrobial resistance patterns. Nevertheless, the entire infection represents a single genotype, or strain. Among mycobacterial species, one would predict that virulent pathogens transmitted from person to person (e.g. Mycobacterium tuberculosis) would be acquired as monoclonal infection, but that non-tuberculous mycobacteria, which are inherently less pathogenic and are transmitted from polymicrobial environmental sources (e.g. soil, water), might sometimes be acquired as a polymicrobial infection or as a monomicrobial polyclonal infection. Although the issue has not been adequately studied in M. tuberculosis, available data suggest that most infections with this species are monoclonal, with occasional polyclonal disease. It is not clear whether the apparent polyclonal infections reported for M. tuberculosis represent concurrently acquired polyclonal infection or sequential acquisition of diverse strains (i.e. superinfection). Non-tuberculous mycobacteria are acquired from the environment, and multiple studies have documented both polymicrobial mycobacterial infections and also monomicrobial polyclonal mycobacterial infection (hereafter referred to as "polyclonal" infection). In the following sections we will review the methods used to detect polyclonal infection with organisms of the Mycobacterium avium complex (MAC) and discuss the implications of polyclonal infection for the epidemiology, pathogenesis, treatment and prophylaxis of infections due to MAC.