Abstract
In an outbreak of multidrug-resistant tuberculosis, the outbreak strain had an Asp516Tyr rpoB gene mutation. Phenotypically, low-level rifampicin (RMP) resistance (minimum inhibitory concentration [MIC] 1-2 mg/l) was observed. Based on drug susceptibility test results, three patients were treated with 12-15 month rifabutin-based regimens and one with a 12-month RMP-based regimen. We retrospectively performed pharmacokinetic calculations to assess the potential for RMP treatment, from which we conclude that MICs for RMP up to 1 μg/ml may be safely overcome by applying 20 mg/kg RMP doses in treatment regimens.
MeSH terms
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Adult
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Antibiotics, Antitubercular / administration & dosage
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Antibiotics, Antitubercular / pharmacokinetics
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Antibiotics, Antitubercular / pharmacology*
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Dose-Response Relationship, Drug
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Drug Resistance, Bacterial
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Female
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Humans
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Male
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Microbial Sensitivity Tests
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Middle Aged
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Mutation
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / isolation & purification
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Retrospective Studies
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Rifabutin / administration & dosage
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Rifabutin / pharmacokinetics
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Rifabutin / pharmacology*
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Tuberculosis / drug therapy*
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Tuberculosis / microbiology
Substances
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Antibiotics, Antitubercular
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Rifabutin