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 microg/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.
Bifani, P; Mathema, B; Kurepina, N; Shashkina, E; Bertout, J; Blanchis, AS; Moghazeh, S; Driscoll, J; Gicquel, B; Frothingham, R; Kreiswirth, BN
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