Pyrazinamide susceptibility and pncA mutation profile of Mycobacterium tuberculosis among multi-drug resistant tuberculosis patients in Bangladesh [PublishAheadOfPrint]

Pyrazinamide (PZA) is a front line anti-tuberculosis (anti-TB) drug used in both first and second line treatment regimen. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed leading to the scarcity of data. Bangladesh is both a high TB and multi-drug resistant (MDR-TB) burden country but to our knowledge the published data on PZA susceptibility is limited, especially among MDR-TB patients. We aimed to analyze the PZA susceptibility pattern of Mycobacterium tuberculosis (MTB) isolates from MDR-TB patients and to correlate pncA mutation with PZA resistance in Bangladesh. A total of 169 confirmed MDR-TB isolates from a pool of specimens collected in a nationwide surveillance study were included in this analysis. All the isolates were tested for phenotypic PZA susceptibility in BACTEC MGIT culture medium and pncA gene was sequenced. We also correlated different clinical information and treatment outcomes with PZA susceptibility. We found that 45% isolates were phenotypically PZA resistant. The sequencing of pncA gene revealed high concordance (82.2%) with phenotypic results. A total of 64 different mutations were found and 9 isolates harbored multiple mutations. We detected 27 new pncA mutations. We did not find any significant correlation between different clinical categories, genetic lineage or treatment outcome groups with PZA susceptibility. Considering turnaround time, sequencing would be the more feasible option to determine PZA susceptibility and further studies to investigate the minimum inhibitory concentration of PZA should be conducted to figure out an effective dose of the drug.

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