title: Genotypic analysis of multidrug-resistant tuberculosis isolates from extra pulmonary tuberculosis cases in tertiary care centers in Northern India.
abstract: OBJECTIVE
  Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The diagnosis of MDR-TB is of paramount importance in establishing appropriate clinical management and infection control measures. Rapid detection of MDR-TB allows the establishment of an effective treatment regimen, minimizes the risk of further resistance, and limits the spread of drug-resistant strains. The aim of this study is to determine the genotypic characterization of MDR-TB isolates from extra pulmonary tuberculosis (EPTB) cases in tertiary care centers in Northern India.
  
  
  METHODS
  This study was a prospective study. In total, 756 extra pulmonary specimens were collected from patients with suspected tuberculosis in two tertiary care hospitals in Northern India. Specimens were processed for Ziehl-Neelsen staining, culture, and first-line drug susceptibility test using BacT/ALERT 3D system and GenoType MTBDRplus assay for genotypic analysis of MDR-TB. MDR-TB strains were further processed by novel multiplex polymerase chain reaction for rapid identification of Beijing and non-Beijing strains associated with MDR-TB.
  
  
  RESULTS
  Of these 164 Mycobacterium tuberculosis complex isolates, 100 (60.9%) strains were fully susceptible and 64 (39.1%) strains were resistant. We noted that the prevalence of MDR-TB among EPTB was 22 (13.4%). The prevalence of MDR-TB was 11.4% in new cases and 19.1% in previously treated cases (p<0.05). Ser531Leu mutation was the predominant mutation noted, and Ser315Thr mutation was more prevalent among the MDR-TB isolates (p<0.05). The proportion of Beijing strains was significantly higher among MDR-TB strains (72.7%, p<0.05).
  
  
  CONCLUSIONS
  The prevalence (13.4%) of MDR-TB among EPTB was high, and the most prominent mutations in rpoB, katG, and inhA genes were S531L (67.3%), S315T1 (94.5%), and C15T (20%), respectively. Beijing stains are significantly associated with MDR-TB among EPTB in this region. We found that the transmission of prominent mutations contributes to an unexpected increase in primary resistance, including MDR-TB cases in Northern India.
authors.affiliation: Department of Microbiology, All India Institute of Medical Sciences, Jodhpur, India. Electronic address: anandmaurya1@gmail.com.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Maurya
authors.affiliation: Department of Microbiology, All India Institute of Medical Sciences, Jodhpur, India.
authors.forename: Vijaya L
authors.initials: VL
authors.lastname: Nag
authors.affiliation: Department of Pulmonary Medicine, King George's Medical University, Lucknow, India.
authors.forename: Surya
authors.initials: S
authors.lastname: Kant
authors.affiliation: Department of Pulmonary Medicine, King George's Medical University, Lucknow, India.
authors.forename: Ramawadh S
authors.initials: RS
authors.lastname: Kushwaha
authors.affiliation: Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Tapan N
authors.initials: TN
authors.lastname: Dhole
keywords: Multidrug-resistant tuberculosis; Mycobacterium tuberculosis complex; Tuberculosis