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

Epidemiologic Correlates of Pyrazinamide-Resistant Mycobacterium tuberculosis in New York City

“…The prevalence of PZA r has been reported to range from 0.8 to 10% among patients with non-MDR TB and from 10 to 85% among patients with MDR TB worldwide (4,29,30). During the study period, TB caused by PZA r M. tuberculosis in NYC was 50% higher than the national average and 20% higher among patients with MDR TB (31).…”

“…PZA acts synergistically with other TB drugs to accelerate culture conversion and reduce the risk of relapse among patients with drug-susceptible TB (1). In patients with multidrug-resistant (MDR) TB, defined as resistance to at least isoniazid (INH) and rifampin (RIF), inclusion of PZA is recommended to reduce the treatment duration (2,3), while optimizing MDR TB treatment regimens based on PZA susceptibility may improve clinical outcomes (4). Due to its well-documented sterilizing capability, PZA has been included in several new TB drug regimens (5)(6)(7).…”

Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

“…Phenotypic DST of M. tuberculosis for pyrazinamide (most effective at pH 5.6) is not routinely performed because of the requirements for precise acidic conditions which prevent the growth of about 20% of the isolates [34,35]. Furthermore, the inoculum size also has profound effects on DST results as larger inoculum may lead to alkalization of the medium causing false PZA resistance [34][35][36]. Nearly 90% of pyrazinamide-resistant M. tuberculosis isolates contain mutations in pncA gene [37].…”

Rapid Detection of Mycobacterium tuberculosis and Pyrazinamide Susceptibility Related topncAMutations in Sputum Specimens through an Integrated Gene-to-Protein Function Approach

“…Since most PZA-resistant M. tuberculosis isolates (72 to 97%) carry mutations in the coding region of the pncA gene (GenBank accession number U59967) (17)(18)(19), genotypic methods to detect pncA mutations, especially direct sequencing of the pncA gene, are being considered more reliable and accurate methods to predict PZA susceptibility (20)(21)(22)(23)(24). A few PZA-resistant strains do not have pncA mutations, and new resistance mechanisms due to rpsA mutation have been proposed (25), but due to their rarity, pncA sequencing is still considered the most reliable method for detection of PZA susceptibility (20).…”

“…A few PZA-resistant strains do not have pncA mutations, and new resistance mechanisms due to rpsA mutation have been proposed (25), but due to their rarity, pncA sequencing is still considered the most reliable method for detection of PZA susceptibility (20). An open-access database (Tuberculosis Drug Resistance Mutation Database [TB-DRMD; www .tbdreamdb.com]) has collected pncA mutations leading to PZA resistance found in previous studies (26).…”