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.

RESULT:

POA efflux rate predicted PZA resistance with 70.83%-92.85% sensitivity and 100% specificity compared with BACTEC 460.

CONCLUSION:

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: Mirko Zimic, Sebastian Loli, Robert H Gilman, Andrés Gutierrez, Patricia Fuentes, Milagros Cotrina, Daniela Kirwan, Patricia Sheen
• Journal: Microbial drug resistance (Larchmont, N.Y.) (Microb Drug Resist) Vol. 18 Issue 4 Pg. 372-5 (Aug 2012) ISSN: 1931-8448 [Electronic] United States
• PMID: 22372927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antitubercular Agents
• Pyrazinamide
• pyrazinoic acid

Topics

• Antitubercular Agents (metabolism, pharmacology)
• Biological Transport (physiology)
• Biotransformation
• Drug Resistance, Bacterial (physiology)
• Humans
• Kinetics
• Microbial Sensitivity Tests
• Mycobacterium tuberculosis (drug effects, isolation & purification, metabolism)
• Pyrazinamide (analogs & derivatives, metabolism, pharmacology)
• Regression Analysis
• Reproducibility of Results
• Sensitivity and Specificity
• Tuberculosis, Pulmonary (microbiology)