Pyrazinamide is not active in vitro against Mycobacterium avium complex

Strains of M. tuberculosis that elaborate pyrazinamidase are typically susceptible in vitro and in vivo to pyrazinamide (PZA). However, we found that 33 strains of M. avium complex (MAC), all of which were pyrazinamidase-positive, were resistant in vitro to a high concentration (100 µg/ml) of PZA when tested at low pH in 7H12 broth by radiometric (BACTEC) method. The drug was equally ineffective against these bacteria within cultured normal human macrophages. We conclude that the pyrazinamidase test is not suitable for susceptibility studies against M. avium complex. On the basis of our in vitro studies, which support earlier data, we believe that PZA is not appropriate for therapy of MAC disease.