title: Predicting differential rifamycin resistance in clinical Mycobacterium tuberculosis isolates by specific rpoB mutations.
abstract: METHODS
  Rifampin (RMP) resistant Mycobacterium tuberculosis is usually assumed to be resistant to all rifamycins. Increasing evidence indicates, however, that some rpoB mutations, detectable by rapid molecular diagnostics, confer resistance to RMP but not to rifabutin (RBT), suggesting that RBT may be effective for the treatment of M. tuberculosis with these mutations.
  
  
  OBJECTIVE
  To determine if specific rpoB mutations reliably predict differential phenotypic resistance to RMP and RBT.
  
  
  METHODS
  We selected 60 clinical M. tuberculosis isolates from a repository of multinational multidrug-resistant tuberculosis isolates and stratified them into two groups: 1) those with rpoB mutations suspected to confer differential resistance to RMP and RBT, and 2) those expected to be cross-resistant to RMP and RBT. These assumptions were tested by comparing the phenotypic susceptibilities of RMP/RBT with those predicted by mutations in the rpoB gene.
  
  
  RESULTS
  Of 20 suspected RMP-resistant/RBT-susceptible isolates, 15 were RMP-resistant but RBT-susceptible, 3 were RMP- and RBT-susceptible, and 2 were cross-resistant to both RMP and RBT. In comparison, 40 of 40 suspected cross-resistant isolates were both RMP- and RBT-resistant.
  
  
  CONCLUSIONS
  Our data support the association between specific rpoB mutations and differential resistance of M. tuberculosis to RMP and RBT. Clinical studies are required to investigate the efficacy of RBT in the treatment of M. tuberculosis harboring these mutations.
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, USA.
authors.forename: W
authors.initials: W
authors.lastname: ElMaraachli
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, USA.
authors.forename: M
authors.initials: M
authors.lastname: Slater
authors.affiliation: California Department of Public Health, Richmond, California, USA.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Berrada
authors.affiliation: California Department of Public Health, Richmond, California, USA.
authors.forename: S-Y G
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, USA.
authors.forename: A
authors.initials: A
authors.lastname: Catanzaro
authors.affiliation: California Department of Public Health, Richmond, California, USA.
authors.forename: E
authors.initials: E
authors.lastname: Desmond
authors.affiliation: Department of Microbiology, P D Hinduja Hospital Medical Research Centre, Veer Sarvarkar Marg, Mumbai, India.
authors.forename: C
authors.initials: C
authors.lastname: Rodrigues
authors.affiliation: Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: T C
authors.initials: TC
authors.lastname: Victor
authors.affiliation: Microbiology and Morphology Laboratory, Institute of Phthisiopneumology, Chisinau, Moldova.
authors.forename: V
authors.initials: V
authors.lastname: Crudu
authors.affiliation: Tropical Disease Foundation/Makati Medical Center, Makati City, The Philippines.
authors.forename: M T
authors.initials: MT
authors.lastname: Gler
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Rodwell
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012189:Retrospective Studies; D017828:Rifabutin / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D017828:Rifabutin; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin