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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Serum drug concentrations predictive of pulmonary tuberculosis outcomes
Journal of Infectious Diseases, Volume 208, No. 9, Year 2013
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Description
Background. Based on a hollow-fiber system model of tuberculosis, we hypothesize that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic variability.Methods. Clinical and pharmacokinetic data were prospectively collected from 142 tuberculosis patients in Western Cape, South Africa. Compartmental pharmacokinetic parameters of isoniazid, rifampin, and pyrazinamide were identified for each patient. Patients were then followed for up to 2 years. Classification and regression tree analysis was used to identify and rank clinical predictors of poor long-term outcome such as microbiologic failure or death, or relapse.Results. Drug concentrations and pharmacokinetics varied widely between patients. Poor long-term outcomes were encountered in 35 (25%) patients. The 3 top predictors of poor long-term outcome, by rank of importance, were a pyrazinamide 24-hour area under the concentration-time curve (AUC) ≤ 363 mg·h/L, rifampin AUC ≤ 13 mg·h/L, and isoniazid AUC ≤ 52 mg·h/L. Poor outcomes were encountered in 32/78 patients with the AUC of at least 1 drug below the identified threshold vs 3/64 without (odds ratio = 14.14; 95% confidence interval, 4.08-49.08). Low rifampin and isoniazid peak and AUC concentrations preceded all cases of acquired drug resistance.Conclusions. Low drug AUCs are predictive of clinical outcomes in tuberculosis patients. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3789573/bin/supp_208_9_1464__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3789573/bin/supp_jit352_jit352supp_table1.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3789573/bin/supp_jit352_jit352supp_table2.doc
Authors & Co-Authors
Pasipanodya, Jotam Garaimunashe
United States, Dallas
Ut Southwestern Medical Center
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
Burger, André
South Africa, Worcester
Brewelskloof Hospital
Wash, Peter A.
South Africa, Worcester
Brewelskloof Hospital
Smith, Peter John
South Africa, Worcester
Brewelskloof Hospital
Gumbo, Tawanda
United States, Dallas
Ut Southwestern Medical Center
Statistics
Citations: 400
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1093/infdis/jit352
ISSN:
00221899
Research Areas
Health System And Policy
Study Design
Case-Control Study
Study Locations
South Africa