A New Approach for Pyrazinamide Susceptibility Testing inMycobacterium tuberculosis

• DOI: 10.1089/mdr.2011.0207
• Publication Date: 2012-02-28T16:30:43Z
• Authors: Mirko Zimic; Sebastian Loli; Robert H. Gilman; Andrés Gutierrez; Patricia Fuentes; Milagros Cotrina; Daniela Kirwan; Patricia Sheen
• Keywords: 0301 basic medicine; https://purl.org/pe-repo/ocde/ford#3.01.05; Antitubercular Agents; Bacteria (Microorganisms); Microbial Sensitivity Tests; Bacterial Enzyme; Sensitivity and Specificity; 03 medical and health sciences; Drug Resistance, Bacterial; Pyrazinoic Acid; Humans; Drug Resistance Bacterial; Tuberculosis, Pulmonary; Biotransformation; Tuberculosis Pulmonary; Antibiotic Sensitivity; Reproducibility of Results; Biological Transport; Mycobacterium tuberculosis; Pyrazinamide; Culture Medium; 3. Good health; Kinetics; Antibiotic Resistance; Intermethod Comparison; Parameters; Bacterium Culture; Regression Analysis; Reproducibility Of Results; Carrier Protein; Prediction; Mycobacterium Tuberculosis; Sensitivity And Specificity

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.To evaluate the rate of POA extrusion from Mycobacterium tuberculosis as a parameter to detect PZA resistance.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.POA efflux rate predicted PZA resistance with 70.83%-92.85% sensitivity and 100% specificity compared with BACTEC 460.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.