Isoniazid and rifampicin resistance mutations and their effect on second-line anti-tuberculosis treatment

Dereje Abate, Y. Tedla, D. Meressa, G. Ameni

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

SETTING: St Peter's TB Specialized Hospital, Addis Ababa, Ethiopia. OBJECTIVE: To estimate the prevalence of mutations that cause resistance to isoniazid (INH) and rifampicin (RMP) and assess the effects of these mutations on second-line anti-tuberculosis treatment. DESIGN: GenoType®MTBDRplus assay results and clinical data documented at St Peter's TB Specialized Hospital over 3 years were retrospectively collected and analysed. RESULTS: The results indicated that 68.7% (n = 470) of RMP-resistant isolates had mutations at codon 531 (S531L) of the rpoB gene, while 93% (n = 481) of the INH-resistant isolates had mutations at codon 315 (S315T1) of the katG gene. The proportion of inhA mutations was 0.8% (n = 481). Treatment outcome was unfavourable in 23.7% (n = 76) of patients treated with second-line anti-tuberculosis drugs. Mutations in other codons of the rpoB gene (P > 0.05) and in the inhA promoter region (P > 0.05) were not associated with unfavourable treatment outcomes. CONCLUSION: The predominant mutations in RMP and INH resistance were observed at codons 531 and 315 in the rpoB and katG genes, respectively. Mutations in the inhA region were rare, which shows its minimal contribution to the development of resistance to ethionamide. This also suggests that treating multi-drug-resistant TB patients with high doses of INH may have little effect.

Original languageEnglish
Pages (from-to)946-951
Number of pages6
JournalInternational Journal of Tuberculosis and Lung Disease
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 1 2014
Externally publishedYes

Keywords

  • Ethionamide
  • InhA
  • KatG
  • Multidrug-resistant tuberculosis
  • RpoB

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

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