title: The impact of isoniazid resistance on the treatment outcomes of smear positive re-treatment tuberculosis patients in the state of Andhra Pradesh, India.
abstract: BACKGROUND
  Multi drug resistant and rifampicin resistant TB patients in India are treated with the World Health Organization (WHO) recommended standardized treatment regimens but no guidelines are available for the management of isoniazid (INH) resistant TB patients. There have been concerns that the standard eight-month retreatment regimen being used in India (2H3R3Z3E3S3/1H3R3Z3E3/5H3R3E3; H-Isoniazid; R-Rifampicin; Z-Pyrazinamide; E-Ethambutol; S-Streptomycin) may be inadequate to treat INH resistant TB cases and leads to poor treatment outcomes. We aimed to assess if INH resistance is associated with unfavorable treatment outcomes (death, default, failure and transferred out) among a cohort of smear positive retreatment TB patients registered in three districts of Andhra Pradesh, India.
  
  
  METHODS
  We conducted a retrospective record review of all smear positive retreatment TB patients without rifampicin resistance registered during April-December 2011.
  
  
  RESULTS
  Of 1,947 TB patients, 1,127 (58%) were tested with LPA-50 (4%) were rifampicin resistant, 933 (84%) were sensitive to INH and rifampicin and 144 (12%) were INH resistant. Of 144 INH resistant cases, 64 (44%) had poor treatment outcomes (25 (17%) default, 22 (15%) death, 12 (8%) failure and 5 (3%) transfer out) as compared to 287 (31%) among INH sensitive cases [aRR 1.46; 95%CI (1.19-1.78)].
  
  
  CONCLUSIONS
  Our study confirms that INH resistance is independently associated with unfavorable treatment outcomes among smear positive retreatment TB patients, indicating that the current treatment regimen may be inadequate. These findings call for an urgent need for randomized controlled trials to discover the most effective treatment regimen for managing INH resistant TB.
authors.affiliation: State Tuberculosis Training and Demonstration Center, Directorate General of Health Services, Government of Andhra Pradesh, Hyderabad, India.
authors.forename: Dorai
authors.initials: D
authors.lastname: Deepa
authors.forename: Shanta
authors.initials: S
authors.lastname: Achanta
authors.forename: Jyoti
authors.initials: J
authors.lastname: Jaju
authors.forename: Koteswara
authors.initials: K
authors.lastname: Rao
authors.forename: Rani
authors.initials: R
authors.lastname: Samyukta
authors.forename: Mareli
authors.initials: M
authors.lastname: Claassens
authors.forename: Ajay M V
authors.initials: AM
authors.lastname: Kumar
authors.forename: Vishnu
authors.initials: V
authors.lastname: Ph
mesh_terms: D000328:Adult; D003710:Demography; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D006801:Humans; D007194:India; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D007538:Isoniazid