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Subtherapeutic Rifampicin Concentration Is Associated With Unfavorable Tuberculosis Treatment Outcomes.
Ramachandran, Geetha; Chandrasekaran, Padmapriyadarshini; Gaikwad, Sanjay; Agibothu Kupparam, Hemanth Kumar; Thiruvengadam, Kannan; Gupte, Nikhil; Paradkar, Mandar; Dhanasekaran, Kavitha; Sivaramakrishnan, Gomathi Narayan; Kagal, Anju; Thomas, Beena; Pradhan, Neeta; Kadam, Dileep; Hanna, Luke Elizabeth; Balasubramanian, Usha; Kulkarni, Vandana; Murali, Lakshmi; Golub, Jonathan; Gupte, Akshay; Shivakumar, Shri Vijay Bala Yogendra; Swaminathan, Soumya; Dooley, Kelly E; Gupta, Amita; Mave, Vidya.
Afiliação
  • Ramachandran G; National Institute for Research in Tuberculosis, Chennai.
  • Chandrasekaran P; National Institute for Research in Tuberculosis, Chennai.
  • Gaikwad S; Byramjee Jeejeebhoy Government Medical College, Pune, India.
  • Agibothu Kupparam HK; National Institute for Research in Tuberculosis, Chennai.
  • Thiruvengadam K; National Institute for Research in Tuberculosis, Chennai.
  • Gupte N; Johns Hopkins School of Medicine, Baltimore, Maryland.
  • Paradkar M; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune.
  • Dhanasekaran K; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune.
  • Sivaramakrishnan GN; National Institute for Research in Tuberculosis, Chennai.
  • Kagal A; National Institute for Research in Tuberculosis, Chennai.
  • Thomas B; Byramjee Jeejeebhoy Government Medical College, Pune, India.
  • Pradhan N; National Institute for Research in Tuberculosis, Chennai.
  • Kadam D; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune.
  • Hanna LE; Byramjee Jeejeebhoy Government Medical College, Pune, India.
  • Balasubramanian U; National Institute for Research in Tuberculosis, Chennai.
  • Kulkarni V; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune.
  • Murali L; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune.
  • Golub J; District Tuberculosis Officer, Thiruvallur, India.
  • Gupte A; Johns Hopkins School of Medicine, Baltimore, Maryland.
  • Shivakumar SVBY; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
  • Swaminathan S; Johns Hopkins School of Medicine, Baltimore, Maryland.
  • Dooley KE; Johns Hopkins University-India Office, Pune.
  • Gupta A; Indian Council of Medical Research, New Delhi.
  • Mave V; Johns Hopkins School of Medicine, Baltimore, Maryland.
Clin Infect Dis ; 70(7): 1463-1470, 2020 03 17.
Article em En | MEDLINE | ID: mdl-31075166
BACKGROUND: The relationships between first-line drug concentrations and clinically important outcomes among patients with tuberculosis (TB) remain poorly understood. METHODS: We enrolled a prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. The maximum plasma concentration of each drug was determined at months 1 and 5 using blood samples drawn 2 hours postdose. Subtherapeutic cutoffs were: rifampicin <8 µg/mL, isoniazid <3 µg/mL, and pyrazinamide <20 µg/mL. Factors associated with lower log-transformed drug concentrations, unfavorable outcomes (composite of treatment failure, all-cause mortality, and recurrence), and individual outcomes were examined using Poisson regression models. RESULTS: Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were subtherapeutic in 85%, 29%, and 13%, respectively, at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with human immunodeficiency virus coinfection (median, 1.6 vs 4.6 µg/mL; P = .015). Unfavorable outcome was observed in 19%; a 1-µg/mL decrease in rifampicin concentration was independently associated with unfavorable outcome (adjusted incidence rate ratio [aIRR], 1.21 [95% confidence interval {CI}, 1.01-1.47]) and treatment failure (aIRR, 1.16 [95% CI, 1.05-1.28]). A 1-µg/mL decrease in pyrazinamide concentration was associated with recurrence (aIRR, 1.05 [95% CI, 1.01-1.11]). CONCLUSIONS: Rifampicin concentrations were subtherapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rifampina / Tuberculose Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: Asia Idioma: En Revista: Clin Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rifampina / Tuberculose Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: Asia Idioma: En Revista: Clin Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2020 Tipo de documento: Article