Pyrazinamide is 1 of the 4 first-line agents used to treat Mycobacterium tuberculosis infections. It is a unique agent in regards to susceptibility testing because it requires testing under acidic conditions, and it is well documented in relevant literature that current broth methods tend to overcall resistance to this agent. In these cases, the broth susceptibility test indicates that the organism is resistant to pyrazinamide. Since there are only 4 first-line agents for treating Mycobacterium tuberculosis infections, incorrectly excluding 1 of them could reduce the likelihood of successful treatment.
Relevant literature has found that the majority of cases associated with pyrazinamide resistance are due to mutations in the pncA gene. These findings led Mayo Clinic to validate a method for sequencing the pncA gene as an additional tool to confirm broth susceptibility testing results.
Cheodor P, Bertucci L, Wolfe J, et al: Potential for erroneous results indicating resistance when using the Bactec MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to pyrazinamide. J. Clin. Microbiol 2010;48:300-301
Pandey S, Newton S, Upton A, et al: Characterisation of pncA mutations in clinical Mycobacterium tuberculosis isolates in New Zealand. Pathology 2009;41:582-584
Simons SO, van Ingen J, van der Laan T, et al: Validation of pncA gene sequencing in combination with the Mycobacterial Growth Indicator Tube method to test susceptibility of Mycobacterium tuberculosis to pyrazinamide. J. Clin Microbiol 2012;50:428-434