Therapy

Pyrazinamide Resistance Due to Weak Pyrazinamide Acid Efflux

Published in TB and Outbreaks Week, March 15th, 1999

The natural resistance of Mycobacterium kansassi to the antituberculosis agent pyrazinamide is directly related to a weak pyrazinoic acid efflux mechanism.

Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug that requires conversion to the bactericidal compound pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) activity of nicotinamidase to show activity against M. tuberculosis.

Mutations leading to a loss of PZase activity cause PZA resistance in M. tuberculosis. M. kansasii is naturally resistant to PZA and has reduced PZase activity along with an apparently detectable nicotinamidase activity.

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Source: TB and Outbreaks Week (1999-03-15)

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