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Published on: December 14, 2016

Pyrazinamide is not active in vitro against Mycobacterium avium complex

L B Heifets, M D Iseman, A J Crowle

    The American Review of Respiratory Disease
    |December 1, 1986
    PubMed

    Insights

    Pyrazinamide (PZA) is ineffective against Mycobacterium avium complex (MAC) strains, even those producing pyrazinamidase. These findings indicate PZA is unsuitable for treating MAC disease and pyrazinamidase testing is unreliable for MAC susceptibility studies.

    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.

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