title: A new approach for pyrazinamide susceptibility testing in Mycobacterium tuberculosis.
abstract: BACKGROUND
  Pyrazinamide (PZA) is an important drug in the treatment of tuberculosis. Microbiological methods of PZA susceptibility testing are controversial and have low reproducibility. After conversion of PZA into pyrazinoic acid (POA) by the bacterial pyrazinamidase enzyme, the drug is expelled from the bacteria by an efflux pump.
  
  
  OBJECTIVE
  To evaluate the rate of POA extrusion from Mycobacterium tuberculosis as a parameter to detect PZA resistance.
  
  
  METHODS
  The rate of POA extrusion and PZA susceptibility determined by BACTEC 460 were measured for 34 strains in a previous study. PZA resistance was modeled in a logistic regression with the pyrazinoic efflux rate.
  
  
  RESULTS
  POA efflux rate predicted PZA resistance with 70.83%-92.85% sensitivity and 100% specificity compared with BACTEC 460.
  
  
  CONCLUSIONS
  POA efflux rate could be a useful tool for predicting PZA resistance in M. tuberculosis. Further exploration of this approach may lead to the development of new tools for diagnosing PZA resistance, which may be of public health importance.
authors.affiliation: Unidad de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Peru. mirko.zimic@upch.pe
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
authors.forename: Sebastian
authors.initials: S
authors.lastname: Loli
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Andrés
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Patricia
authors.initials: P
authors.lastname: Fuentes
authors.forename: Milagros
authors.initials: M
authors.lastname: Cotrina
authors.forename: Daniela
authors.initials: D
authors.lastname: Kirwan
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheen
mesh_terms: D000995:Antitubercular Agents / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D001711:Biotransformation; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D012044:Regression Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014397:Tuberculosis, Pulmonary / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; C005296:pyrazinoic acid