title: Genetic diversity and evidence for acquired antimicrobial resistance in Mycobacterium tuberculosis at a large hospital in South India.
abstract: OBJECTIVE
  To assess genetic diversity and drug resistance of Mycobacterium tuberculosis isolates collected at Christian Medical College Hospital (CMCH), Vellore, India, between July 1995 and May 1996.
  
  
  METHODS
  Isolates were subjected to IS6110-based restriction fragment length polymorphism (RFLP) analysis and tested for resistance to isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide, and DNA from selected strains was sequenced in regions associated with drug resistance.
  
  
  RESULTS
  One hundred and one M. tuberculosis isolates were collected from 87 patients with pulmonary tuberculosis. Charts of 69 patients were reviewed for history of tuberculosis illness and treatment. DNA from 29 strains was sequenced in katG, rpoB, and gyrA, and sometimes pncA regions. Analysis by RFLP revealed a high degree of genetic diversity, with no identifiable clusters of infection. Of the strains tested, 51% were resistant to at least one antibiotic, and 43% were resistant to more than one drug. There was a high rate of resistance observed in patients whose charts indicated a history of improperly administered tuberculosis treatment, whereas little drug resistance was observed in patients never previously treated for tuberculosis. Sequencing of genes associated with drug resistance revealed several previously unreported mutations in resistant strains.
  
  
  CONCLUSIONS
  This analysis suggests that the cases of tuberculosis in the sample are largely reactivation of long-standing infections and that the drug resistance among patients in CMCH is largely acquired or secondary rather than attributable to the spread of drug-resistant strains.
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Harris
authors.forename: U
authors.initials: U
authors.lastname: Mukundan
authors.forename: J M
authors.initials: JM
authors.lastname: Musser
authors.forename: B N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: M K
authors.initials: MK
authors.lastname: Lalitha
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D014644:Genetic Variation; D006761:Hospitals; D006801:Humans; D007194:India / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements