High degree of multi-drug resistance and hetero-resistance in pulmonary TB patients from Punjab state of India

Tuberculosis (Edinb). 2014 Jan;94(1):73-80. doi: 10.1016/j.tube.2013.10.001. Epub 2013 Oct 22.


Line Probe Assays (LPAs) have been recommended for rapid screening of MDR-TB. Aims of this study were (1) to compare the performance of LPA with standard Bactec MGIT 960 system and (2) to ascertain the pattern of genetic mutations in the resistance isolates. In phase I, a total of 141 Mycobacterium tuberculosis isolates from our routine laboratory were tested by LPA and Bactec MGIT 960 for DST. In phase II, 578 sputum specimens of suspected DR-TB patients were received from the Punjab state of India. Of them 438 specimens or their cultures were subjected to LPA. The presence of mutant bands with their corresponding wild type band was identified as "hetero-resistance". In phase I, LPA showed high concordance with 96.4% positive agreement and 97.6% negative agreement with Bactec MGIT 960-DST. In phase II, 12 (2.7%) specimens were detected as invalid by LPA. Of the remaining 426 specimens, 184 (43.1%) had resistance to RIF and 142 (33.3%) to INH while 103 (24.1%) specimens showed resistance to both INH and RIF (MDR-TB) by LPA. Of the 142 INH resistant, 113 (79.5%) showed mutations in katG and 29 (20.4%) in inhA. A high rate of hetero-resistance pattern was observed in rpoB gene (28.8%) and katG gene (9.8%). The most frequent mutation was S531L (81.1%) in rpoB region and S315T1 (100%) in katG gene.

Keywords: Isoniazid; Line Probe Assay; MTBDRplus; Mycobacterium tuberculosis; Rifampicin.

Publication types

  • Comparative Study

MeSH terms

  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / genetics
  • Catalase / genetics
  • DNA-Directed RNA Polymerases
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Drug Resistance, Multiple, Bacterial / immunology
  • European Continental Ancestry Group / genetics
  • Female
  • Humans
  • India
  • Male
  • Microbial Sensitivity Tests
  • Molecular Diagnostic Techniques*
  • Mutation*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Sequence Analysis, DNA
  • Sputum / microbiology*
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / genetics*
  • Tuberculosis, Multidrug-Resistant / immunology
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / immunology


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