Pyrazinamide is not active in vitro against Mycobacterium avium complex

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Pyrazinamide (PZA) is a crucial first-line antituberculosis drug.
• Susceptibility to PZA is often linked to pyrazinamidase enzyme activity in Mycobacterium tuberculosis.
• The efficacy of PZA against the Mycobacterium avium complex (MAC) remains less understood.

Purpose of the Study:

• To evaluate the in vitro susceptibility of Mycobacterium avium complex (MAC) strains to pyrazinamide (PZA).
• To determine the utility of the pyrazinamidase test for predicting PZA susceptibility in MAC.
• To assess the effectiveness of PZA against MAC within human macrophages.

Main Methods:

• Radiometric broth microdilution (BACTEC) was used to test PZA susceptibility of 33 pyrazinamidase-positive MAC strains.
• Testing was performed at low pH (5.0) in 7H12 broth.
• Drug efficacy was also assessed against MAC within cultured human macrophages.

Main Results:

• All 33 pyrazinamidase-positive MAC strains exhibited in vitro resistance to a high concentration (100 µg/ml) of PZA.
• PZA demonstrated ineffectiveness against MAC when tested within human macrophages.
• The pyrazinamidase test did not correlate with PZA resistance in MAC.

Conclusions:

• The pyrazinamidase test is not a suitable method for determining PZA susceptibility in MAC.
• Pyrazinamide is not recommended for the treatment of diseases caused by Mycobacterium avium complex.
• These findings support previous data suggesting PZA's limited role in MAC infections.