Drug-Resistant Tuberculosis: Inconsistent Results of Pyrazinamide Susceptibility Testing

‘Z S -MDR-TB’ versus ‘Z R -MDR-TB’: improving treatment of MDR-TB by identifying pyrazinamide susceptibility

“…30 However, PZA susceptibility testing is prone to errors, 3,31,32 which arise from: (i) acidity of the medium required for PZA activity inhibits the growth of Mycobacterium tuberculosis —about 20%–25% of clinical isolates do not grow on acidic 7H10 plates (pH 5.5), and even with pH 6.0 in BACTEC 460 liquid medium, 3.5% of the strains did not grow; 33 and (ii) use of too large an inoculum (over 10 7  bacilli/ml) leads to increase in medium pH, which then inactivates PZA. 34 In a recent study, the MGIT 960 PZA susceptibility testing method was found to be even less reliable than the radioactive BACTEC 460 method giving rise to more false resistant results, presumably due to the larger inoculum used in the MGIT method.…”

Rapid Colorimetric Testing for Pyrazinamide Susceptibility of M. tuberculosis by a PCR-Based In-Vitro Synthesized Pyrazinamidase Method

“…Among them, the radiometric assay (BACTEC 460TB) using pH 6.0 and PZA concentration of 100ug/mL was considered as most reliable and the currently recommended assay (Clinical Laboratory Standard Institute, M24-A2). However, even for this reference method, inconsistent results between different labs have been reported [10], [11]. Previous studies found that the radiometric assay can lead to inconclusive results up to 3.5% of the strains [12], falsely resistant results for at least 0.8% of the strains [13], and falsely susceptible results for some strains [14].…”

Molecular Epidemiological Study of Pyrazinamide-Resistance in Clinical Isolates of Mycobacterium tuberculosis from South India

“…Conventional pyrazinamide susceptibility testing by agar proportion or by Lowenstein–Jensen proportion method is labor intensive and may exhibit high discordance rates among different laboratories as the media pH and other parameters are known to influence the outcome of the susceptibility testing [7]. Automated systems, such as the BACTEC 460 TB system, BACTEC MGIT 960 are commercially available, but are expensive and impractical to use in developing countries where the prevalence of tuberculosis is high.…”