Disputed rpoB mutations can frequently cause important rifampicin resistance among new tuberculosis patients

Int J Tuberc Lung Dis. 2015 Feb;19(2):185-90. doi: 10.5588/ijtld.14.0651.


Setting: Greater Mymensingh area, Bangladesh.

Objectives: To document among new tuberculosis (TB) patients the proportions and treatment outcomes of silent, non-disputed and disputed (generally missed by rapid drug susceptibility testing [DST]) rpoB mutations, and their detection by commercial molecular assays.

Design: Retrospective analysis of rpoB sequences from randomly selected ethanol-preserved diagnostic sputum samples; comparison of sequencing with conventional DST results and standard first-line treatment outcome; retesting of samples with mutations using the Xpert MTB/RIF and GenoType MTBDRplus assays.

Results: Of 1091 samples, 5.8% failed amplification, and six contained other mycobacteria. In 2005 and 2010, respectively 2/500 (0.4%) and 11/522 (2.1%) amplicons showed non-silent mutations. At least 7/13 of these belonged to the disputed group, with 5/7 patients suffering adverse treatment outcome. One silent mutation went undetected by commercial assays. Following routine DST indications, only three cases with a non-silent mutation were eventually detected.

Conclusions: Disputed rpoB mutations may be responsible for the majority of rifampicin (RMP) resistance among new cases, and lead to adverse outcomes of first-line treatment. Silent mutations do not necessarily cause Xpert or line-probe assay false RMP-resistant results. Molecular RMP DST could greatly simplify resistance surveillance, in addition to offering the best prospects for early and accurate individual diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bangladesh
  • DNA-Directed RNA Polymerases
  • Drug Resistance, Bacterial
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Nucleic Acid Amplification Techniques
  • Retrospective Studies
  • Rifampin / pharmacology*
  • Sputum / microbiology
  • Tuberculosis / drug therapy
  • Tuberculosis / microbiology


  • Antitubercular Agents
  • Bacterial Proteins
  • rpoB protein, Mycobacterium tuberculosis
  • DNA-Directed RNA Polymerases
  • Rifampin