Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

Am J Trop Med Hyg. 2016 Dec 7;95(6):1239-1246. doi: 10.4269/ajtmh.15-0711. Epub 2016 Oct 24.


Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism*
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Case-Control Studies
  • Drug Resistance, Bacterial
  • Female
  • Gene Expression Regulation, Bacterial
  • Gene Expression Regulation, Enzymologic
  • Genotype
  • HIV Infections / complications*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Mycobacterium tuberculosis / enzymology*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism
  • Tuberculosis / complications*
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control*
  • Young Adult


  • Antitubercular Agents
  • Amidohydrolases
  • PncA protein, Mycobacterium tuberculosis