The Evolution of Drug Resistance in Mycobacterium tuberculosis: From a Mono–Rifampin-Resistant Cluster into Increasingly Multidrug-Resistant Variants in an HIV-Seropositive Population

We describe the genotypic and phenotypic characteristics of a mono-rifampin-resistant (RIF R ) Mycobacterium tuberculosis strain cluster (designated AU-RIF R ) and the acquisition of additional drug resistance. Drug susceptibility, sequences of regions that determine drug resistance, and basic clinical data were examined. A rare codon duplication (514 TTC ) in rpoB conferring high levels of RIF R (minimum inhibitory concentration of >256 μg/mL) in 29 isolates was identified. AU-RIF R strains developed secondary resistance to isoniazid and 7 resistance combinations to 6 different antibiotics. Patients infected with AU-RIF R strains were primarily immunocompromised. These data suggest that host factors, such as HIV status, may allow dissemination of mono-RIF R strains and facilitate the accumulation of additional drug resistance.