title: Low-level rifampicin-resistant Mycobacterium tuberculosis strains raise a new therapeutic challenge.
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.
authors.affiliation: Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. jakko.vaningen@gmail.com
authors.forename: J
authors.initials: J
authors.lastname: van Ingen
authors.forename: R
authors.initials: R
authors.lastname: Aarnoutse
authors.forename: G
authors.initials: G
authors.lastname: de Vries
authors.forename: M J
authors.initials: MJ
authors.lastname: Boeree
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012189:Retrospective Studies; D017828:Rifabutin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin