Ontology highlight
ABSTRACT: 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.
SUBMITTER: Pasipanodya JG
PROVIDER: S-EPMC3789573 | biostudies-literature | 2013 Nov
REPOSITORIES: biostudies-literature
Pasipanodya Jotam G JG McIlleron Helen H Burger André A Wash Peter A PA Smith Peter P Gumbo Tawanda T
The Journal of infectious diseases 20130729 9
<h4>Background</h4>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.<h4>Methods</h4>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. Patien ...[more]