Abstract
ABSTRACTPyrazinamide (PZA) is a frontline antituberculosis (anti-TB) drug used in both first- and second-line treatment regimens. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed, leading to a scarcity of data on susceptibility to PZA. Bangladesh is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB), but to our knowledge, published data on rates of PZA susceptibility (PZAs), especially among MDR-TB patients, are limited. We aimed to analyze the PZA susceptibility patterns of Mycobacterium tuberculosis isolates from MDR-TB patients and to correlate the pncA mutation with PZA resistance in Bangladesh. A total of 169 confirmed MDR M. tuberculosis 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 mycobacterial growth indicator tube (MGIT) culture medium, and the pncA gene was sequenced. We also correlated different types of clinical information and treatment outcomes with PZA susceptibility. We found that 45% of isolates were phenotypically PZA resistant. Sequencing of the pncA gene revealed a high concordance (82.2%) between the pncA gene sequence and the phenotypic assay 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 the different clinical categories, the genetic lineage, or treatment outcome group and PZA susceptibility. Considering the turnaround time, sequencing would be the more feasible option to determine PZA susceptibility, and further studies to investigate the MIC of PZA should be conducted to determine an effective dose of the drug.
Highlights
Pyrazinamide (PZA) is a frontline antituberculosis drug used in both first- and second-line treatment regimens
The frequency of PZA resistance (PZAr) was higher among MDR isolates with ethambutol (EMB) resistance (61.5%; 95% CI, 35.5 to 82.3%) than among isolates with sole INH and RIF resistance (6.7%; 95% CI, 1.2 to 29.8%) and MDR isolates with sole streptomycin (STR) resistance (15.8%; 95% CI, 5.5 to 37.6%) (Table 1)
Because of the possibility of a false PZA susceptibility result in a mycobacterial growth indicator tube (MGIT) due to an inoculum effect, we repeated the phenotypic PZA susceptibility test for 16 isolates
Summary
Pyrazinamide (PZA) is a frontline antituberculosis (anti-TB) drug used in both first- and second-line treatment regimens. We aimed to analyze the PZA susceptibility patterns of Mycobacterium tuberculosis isolates from MDR-TB patients and to correlate the pncA mutation with PZA resistance in Bangladesh. The mutation types include the substitution of nucleotides and the insertion and deletion of single or multiple nucleotides in the coding and upstream promoter regions of the pncA gene. Though the prevalence of PZAr is higher in multidrug-resistant (MDR) TB (MDR-TB) cases, due to technical difficulties, the phenotypic PZA susceptibility test is rarely performed [19]. Most patients infected with PZAr strains fail to get appropriate treatment [22] This is the main reason behind the scarcity of data regarding PZA susceptibility. Another study used MDR M. tuberculosis isolates from Bangladesh and compared the results of the pyrazinamidase assay with the pncA gene mutations found [11]. Different studies from around the world have shown that roughly 2 to 7.5% of non-MDR-TB cases, 36 to 85% of MDR-TB cases, and about 16% of all TB cases are caused by PZAr isolates [14, 24,25,26]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
