title: Isoniazid and rifampicin resistance mutations and their effect on second-line anti-tuberculosis treatment.
abstract: METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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 multidrug-resistant TB patients with high doses of INH may have little effect.
authors.affiliation: <label>*</label>Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: D
authors.initials: D
authors.lastname: Abate
authors.affiliation: <label><sup>†</sup></label>St Peter TB Specialised Hospital, Addis Ababa, Ethiopia.
authors.forename: Y
authors.initials: Y
authors.lastname: Tedla
authors.affiliation: <label><sup>†</sup></label>St Peter TB Specialised Hospital, Addis Ababa, Ethiopia.
authors.forename: D
authors.initials: D
authors.lastname: Meressa
authors.affiliation: <label>*</label>Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: G
authors.initials: G
authors.lastname: Ameni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D003062:Codon / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005000:Ethionamide / Q000494:pharmacology / Q000627:therapeutic use; D005002:Ethiopia; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D003062:Codon; D005000:Ethionamide; D007538:Isoniazid; D012293:Rifampin