Pyrazinamide Drug Resistance in Mycobacterium Tuberculosis: A Minireview

Abstract

Pyrazinamide (PZA) is a nicotinamide analog that is used as a frontline drug to treat tuberculosis (TB). It has special place in modern TB therapy, as it appears to kill a population of semi dormant tubercle bacilli persisting in the body. It is important drug because of its sterilizing activity against semi dormant tubercle bacilli. Although PZA has a very high in vivo activity, it’s in vitro activity is not apparent unless an acidic environment is available, which makes PZA drug susceptibility testing (DST) more difficult by conventional methods. Being a nicotinamide analogue, PZA needs to be converted into its active bactericidal form pyrazinoic acid (POA) by the mycobacterial enzyme pyrazinamidase (PZase).PZase is encoded by pncA, and mutations in this gene have been demonstrated as the major mechanism of PZA resistance.PZA-resistant Mycobacterium tuberculosis strains are usually correlated well with defective PZase activity. The rapid detection of PZA resistance is of utmost importance for an effective treatment and also to avoid further spread of MDR strains. Analysis of the pncAgene provides rapid and useful information regarding PZA susceptibility in M. tuberculosis and may therefore contribute to early optimization of treatment. The diversity of methods currently used in clinical laboratories for the detection of PZA resistance in M. tuberculosis isolates causes inconsistent results of PZA DST and such inconsistent results of PZA DST have been reported by a number of laboratories by various methods, including the qualitative BACTEC test. Therefore, it is essential to elucidate the genetic basis of clinical resistance and to correlate phenotypic and molecular resistance data.