Impact of pyrazinamide resistance on multidrug-resistant tuberculosis in Karakalpakstan, Uzbekistan

Int J Tuberc Lung Dis. 2018 May 1;22(5):544-550. doi: 10.5588/ijtld.17.0483.

Abstract

Setting: The World Health Organization (WHO) recommends the inclusion of pyrazinamide (PZA) in treatment regimens for multidrug-resistant tuberculosis (MDR-TB) unless resistance has been confirmed.

Objective: To investigate the association between PZA susceptibility and MDR-TB treatment outcome among patients treated with a PZA-containing regimen and whether the duration of the intensive phase of the PZA-containing regimen affected treatment outcome.

Design: We conducted a retrospective cohort study including all eligible MDR-TB patients starting treatment in 2003-2013 in the TB programme in Karakalpakstan, Uzbekistan. PZA drug susceptibility testing (DST) using liquid culture was performed, and outcomes were classified according to the WHO 2013 definitions.

Results: Of 2446 MDR-TB patients included, 832 (34.0%) had an available baseline PZA DST result, 612 (73.6%) of whom were PZA-resistant. We found no association between treatment success and PZA susceptibility (adjusted odds ratio [aOR] 0.86, 95%CI 0.51-1.44, P = 0.6) in patients treated with PZA. Furthermore, among patients with no baseline PZA DST result, no evidence was seen of an association between treatment success and PZA treatment duration (aOR 0.86, 95%CI 0.49-1.51, P = 0.6).

Conclusion: Treatment of MDR-TB with a standard PZA regimen does not appear to improve treatment outcomes, regardless of PZA susceptibility or duration of treatment.

MeSH terms

  • Adult
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Female
  • Humans
  • Logistic Models
  • Male
  • Microbial Sensitivity Tests
  • Multivariate Analysis
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / isolation & purification
  • Pyrazinamide / pharmacology*
  • Pyrazinamide / therapeutic use
  • Retrospective Studies
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / microbiology*
  • Uzbekistan / epidemiology
  • Young Adult

Substances

  • Antitubercular Agents
  • Pyrazinamide