title: The evolution of drug resistance in Mycobacterium tuberculosis: from a mono-rifampin-resistant cluster into increasingly multidrug-resistant variants in an HIV-seropositive population.
abstract: 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.
authors.affiliation: Pasteur Institute, Brussels, Belgium. pbifani@pasteur.be
authors.forename: Pablo
authors.initials: P
authors.lastname: Bifani
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.forename: Natalia
authors.initials: N
authors.lastname: Kurepina
authors.forename: Elena
authors.initials: E
authors.lastname: Shashkina
authors.forename: Julie
authors.initials: J
authors.lastname: Bertout
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Blanchis
authors.forename: Soraya
authors.initials: S
authors.lastname: Moghazeh
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Driscoll
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Richard
authors.initials: R
authors.lastname: Frothingham
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D005075:Biological Evolution; D024901:Drug Resistance, Multiple, Bacterial; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology*; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin