Pyrazinamide resistance in rifampicin discordant tuberculosis

PLoS One. 2022 Sep 21;17(9):e0274688. doi: 10.1371/journal.pone.0274688. eCollection 2022.

Abstract

Introduction: Mycobacterium tuberculosis strains with phenotypically susceptible rpoB mutations (rifampicin discordant) have emerged following implementation of rapid molecular drug resistance testing for tuberculosis. Whilst rifampicin resistance is known to be associated with resistance to other rifamycins (rifapentine and rifabutin) as well as isoniazid and pyrazinamide, rifampicin discordant strains have shown high rates of susceptibility to isoniazid and rifabutin. However, pyrazinamide susceptibly testing results have not been reported.

Materials and methods: We evaluated pyrazinamide resistance in 80 rifampicin discordant and 25 rifampicin and isoniazid susceptible isolates from KwaZulu-Natal in South Africa using Mycobacteria Growth Indicator Tube method and sequencing of the pncA. We also compared susceptibility of pyrazinamide with that of isoniazid.

Results: Pyrazinamide resistance was found in 6/80 (7.5%) rifampicin discordant isolates. All pyrazinamide resistant isolates were also resistant to isoniazid and pyrazinamide resistance was found to be associated with isoniazid resistance. No pyrazinamide resistance was found among the isoniazid susceptible isolates.

Conclusion: Given the low prevalence of pyrazinamide resistance in rifampicin discordant TB, this anti-TB drug still has a significant role in the treatment of these patients. Performing pyrazinamide susceptibility testing remains a challenge, our findings show that isoniazid susceptible isolates are unlikely to be resistant to pyrazinamide among the discordant TB isolates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Humans
  • Isoniazid / pharmacology
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis* / genetics
  • Pyrazinamide / pharmacology
  • Pyrazinamide / therapeutic use
  • Rifabutin
  • Rifampin / pharmacology
  • South Africa / epidemiology
  • Tuberculosis* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / epidemiology

Substances

  • Antitubercular Agents
  • Rifabutin
  • Pyrazinamide
  • Isoniazid
  • Rifampin

Grants and funding

NRM received funding from the University of KwaZulu-Natal for this study. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.