Old drugs, new purpose: retooling existing drugs for optimized treatment of resistant tuberculosis.

Published

Journal Article (Review)

Treatment of drug-resistant tuberculosis is hindered by the high toxicity and poor efficacy of second-line drugs. New compounds must be used together with existing drugs, yet clinical trials to optimize combinations of drugs for drug-resistant tuberculosis are lacking. We conducted an extensive review of existing in vitro, animal, and clinical studies involving World Health Organization-defined group 1, 2, and 4 drugs used in drug-resistant tuberculosis regimens to inform clinical trials and identify critical research questions. Results suggest that optimizing the dosing of pyrazinamide, the injectables, and isoniazid for drug-resistant tuberculosis is a high priority. Additional pharmacokinetic, pharmacodynamic, and toxicodynamic studies are needed for pyrazinamide and ethionamide. Clinical trials of the comparative efficacy and appropriate treatment duration of injectables are recommended. For isoniazid, rapid genotypic tests for Mycobacterium tuberculosis mutations should be nested in clinical trials. Further research focusing on optimization of dose and duration of drugs with activity against drug-resistant tuberculosis is paramount.

Full Text

Duke Authors

Cited Authors

  • Dooley, KE; Mitnick, CD; Ann DeGroote, M; Obuku, E; Belitsky, V; Hamilton, CD; Makhene, M; Shah, S; Brust, JCM; Durakovic, N; Nuermberger, E; Efficacy Subgroup, RESIST-TB,

Published Date

  • August 2012

Published In

Volume / Issue

  • 55 / 4

Start / End Page

  • 572 - 581

PubMed ID

  • 22615332

Pubmed Central ID

  • 22615332

Electronic International Standard Serial Number (EISSN)

  • 1537-6591

Digital Object Identifier (DOI)

  • 10.1093/cid/cis487

Language

  • eng

Conference Location

  • United States