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

Bifani, Pablo; Mathema, Barun; Kurepina, Natalia; Shashkina, Elena; Bertout, Julie; Blanchis, Anne Sophie; Moghazeh, Soraya; Driscoll, Jeffrey; Gicquel, Brigitte; Frothingham, Richard; Kreiswirth, Barry N.
July 2008
Journal of Infectious Diseases;7/1/2008, Vol. 198 Issue 1, p90
Academic Journal
We describe the genotypic and phenotypic characteristics of a mono-rifampin-resistant (RIFR) Mycobacterium tuberculosis strain cluster (designated AU-RIFR) 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 (514TTC) inrpoB conferring high levels of RIFR (minimum inhibitory concentration of >256 μg/mL) in 29 isolates was identified. AU-RIFR strains developed secondary resistance to isoniazid and 7 resistance combinations to 6 different antibiotics. Patients infected with AU-RIFR strains were primarily immunocompromised. These data suggest that host factors, such as HIVstatus, may allow dissemination of mono-RIFR strains and facilitate the accumulation of additional drug resistance.


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