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.
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: L Vásquez-Campos; L Asencios-Solis; E Leo-Hurtado; N Quispe-Torres; E Salazar-Lindo; J Bayona; M C Becerra Journal: Int J Tuberc Lung Dis Date: 2004-04 Impact factor: 2.373
Authors: Elizabeth L Corbett; Catherine J Watt; Neff Walker; Dermot Maher; Brian G Williams; Mario C Raviglione; Christopher Dye Journal: Arch Intern Med Date: 2003-05-12
Authors: Tawanda Gumbo; Emmanuel Chigutsa; Jotam Pasipanodya; Marianne Visser; Paul D van Helden; Frederick A Sirgel; Helen McIlleron Journal: J Antimicrob Chemother Date: 2014-05-12 Impact factor: 5.790