title: Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India.
abstract: The Indian Revised National Tuberculosis (TB) Control Programme uses thrice-weekly treatment with standard drug dosages. The role of plasma drug levels and other factors in determining TB treatment outcomes is not well understood. We aimed to determine the factors influencing the concentrations of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) at 2 h postdosing in adult TB patients and to study the factors impacting TB treatment outcome. We recruited 1,912 adult TB patients (newly treated and retreated patients) with pulmonary/extrapulmonary TB receiving antitubercular treatment (ATT) in the RNTCP in Chennai, India. At steady state, the concentrations of RMP, INH, and PZA were determined at 2 h postdosing after supervised drug administration. A total of 1,648 patients had a favorable outcome, while 264 (14%) had an unfavorable outcome. A total of 91%, 16%, and 17% of the patients had suboptimal concentrations of RMP (<8 μg/ml), INH (<3 μg/ml), and PZA (<20 μg/ml), respectively. Factors associated with treatment outcome were low RMP concentrations (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89 to 0.99;P= 0.036), category II ATT (aOR, 2.39; 95% CI, 1.56 to 3.65;P< 0.001), low body weight (aOR, 0.96; 95% CI, 0.94 to 0.98;P< 0.001), alcohol use (aOR, 2.17; 95% CI, 1.42 to 3.31;P< 0.001), male gender (aOR, 1.92; 95% CI, 1.02 to 3.62;P= 0.043), and baseline INH resistance (aOR, 5.74; 95% CI, 3.12 to 10.59;P< 0.001), which significantly increased the likelihood of an unfavorable outcome in multivariate logistic regression analysis. Further studies are needed to optimize anti-TB drug dosages and improve cure rates. Drug susceptibility testing at the baseline and attention to undernutrition and alcohol dependence are other important interventions.
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India geetha202@rediffmail.com.
authors.forename: Geetha
authors.initials: G
authors.lastname: Ramachandran
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Hemanth Kumar
authors.initials: HK
authors.lastname: Agibothu Kupparam
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Vedhachalam
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Kannan
authors.initials: K
authors.lastname: Thiruvengadam
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Rajagandhi
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Azger
authors.initials: A
authors.lastname: Dusthackeer
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Karunaianantham
authors.affiliation: Chennai Corporation, Chennai, India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Jayapal
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000627:therapeutic use*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D054796:Drug Dosage Calculations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007194:India; D007538:Isoniazid / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011718:Pyrazinamide / Q000097:blood / Q000627:therapeutic use*; D012293:Rifampin / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid; D012293:Rifampin
keywords: isoniazid; pharmacokinetics; pyrazinamide; rifampin; treatment outcome; tuberculosis