Old Drugs, New Purpose: Retooling Existing Drugs for Optimized Treatment of Resistant Tuberculosis | Zendy

Kelly E. Dooley | Zendy; Carole D. Mitnick | Zendy; Mary Ann DeGroote | Zendy; Ekwaro A. Obuku | Zendy; V. Belitsky | Zendy; Carol Hamilton | Zendy; Mamodikoe Makhene | Zendy; Sarita Shah | Zendy; James C. M. Brust | Zendy; N. Durakovic | Zendy; Eric L. Nuermberger | Zendy

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Old Drugs, New Purpose: Retooling Existing Drugs for Optimized Treatment of Resistant Tuberculosis

Author(s) -

Kelly E. Dooley,

Carole D. Mitnick,

Mary Ann DeGroote,

Ekwaro A. Obuku,

V. Belitsky,

Carol Hamilton,

Mamodikoe Makhene,

Sarita Shah,

James C. M. Brust,

N. Durakovic,

Eric L. Nuermberger

Publication year - 2012

Publication title -

clinical infectious diseases

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.44

H-Index - 336

eISSN - 1537-6591

pISSN - 1058-4838

DOI - 10.1093/cid/cis487

Subject(s) - medicine , pyrazinamide , tuberculosis , clinical trial , isoniazid , ethionamide , drug , bedaquiline , mycobacterium tuberculosis , dosing , pharmacology , rifampicin , extensively drug resistant tuberculosis , pharmacodynamics , intensive care medicine , pharmacokinetics , ethambutol , pathology

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.

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