The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Serum Drug Concentrations Predictive of Pulmonary Tuberculosis Outcomes
Open accessAbstract
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.
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Cited by
Ellington, M. J., Ekelund, O., Aarestrup, F. M., Canton, R., Doumith, M., Giske, C., Grundman, H., Hasman, H., Holden, M. T. G., Hopkins, K. L., et al. (2017) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2016.11.012 · Cited by 603
Therapeutic Drug Monitoring in the Treatment of Tuberculosis: An Update
Alsultan, A., & Peloquin, C. A. (2014) · Drugs · doi:10.1007/s40265-014-0222-8 · Cited by 444
Horsburgh, C. R., Barry, C. E., & Lange, C. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1413919 · Cited by 323
A Dose-Ranging Trial to Optimize the Dose of Rifampin in the Treatment of Tuberculosis
Boeree, M. J., Diacon, A. H., Dawson, R., Narunsky, K., du Bois, J., Venter, A., Phillips, P. P. J., Gillespie, S. H., McHugh, T. D., Hoelscher, M., et al. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201407-1264oc · Cited by 309
Aklillu, E., Carrillo, J. A., Makonnen, E., Bertilsson, L., & Djordjevic, N. (2018) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-018-2448-y · Cited by 28
Metadata
- Authors
- Pasipanodya, J. G., McIlleron, H., Burger, A., Wash, P. A., Smith, P., & Gumbo, T.
- Venue
- Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-07-29
- Volume
- 208
- Issue
- 9
- Pages
- 1464-1473
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2107834145
- Cited by
- 444
- References
- 32
- FWCI
- 25.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pasipanodya, J. G., McIlleron, H., Burger, A., Wash, P. A., Smith, P., & Gumbo, T. (2013). Serum Drug Concentrations Predictive of Pulmonary Tuberculosis Outcomes. Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jit352
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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