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.