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

Kelly E. Dooley, Carole D. Mitnick, Mary Ann DeGroote, Ekwaro Obuku, Vera Belitsky, Carol D. Hamilton, Mamodikoe Makhene, Sarita Shah, James C.M. Brust, Nadza Durakovic, Eric Nuermberger

Research output: Contribution to journalReview article

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)572-581
Number of pages10
JournalClinical Infectious Diseases
Volume55
Issue number4
DOIs
StatePublished - Aug 15 2012

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Dooley, K. E., Mitnick, C. D., DeGroote, M. A., Obuku, E., Belitsky, V., Hamilton, C. D., Makhene, M., Shah, S., Brust, J. C. M., Durakovic, N., & Nuermberger, E. (2012). Old drugs, new purpose: Retooling existing drugs for optimized treatment of resistant tuberculosis. Clinical Infectious Diseases, 55(4), 572-581. https://doi.org/10.1093/cid/cis487