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

被引：54

作者：

Dooley, Kelly E. ^{[1
]}

Mitnick, Carole D. ^{[2
]}

DeGroote, Mary Ann ^{[3
]}

Obuku, Ekwaro ^{[4
,5
]}

Belitsky, Vera ^{[6
]}

Hamilton, Carol D. ^{[7
]}

Makhene, Mamodikoe ^{[8
]}

Shah, Sarita ^{[9
]}

Brust, James C. M. ^{[9
]}

Durakovic, Nadza ^{[6
]}

Nuermberger, Eric

机构：

[1] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Baltimore, MD 21287 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Colorado State Univ, Mycobacterial Res Labs, Ft Collins, CO 80523 USA

[4] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[5] AIDS Relief Programme & Joint Clin Res Ctr, Kampala, Uganda

[6] Partners Hlth, Boston, MA USA

[7] Family Hlth Int, Durham, NC USA

[8] NIH, Bethesda, MD 20892 USA

[9] Albert Einstein Coll Med, Bronx, NY 10467 USA

来源：

CLINICAL INFECTIOUS DISEASES | 2012年 / 55卷 / 04期

基金：

美国国家卫生研究院;

关键词：

EARLY BACTERICIDAL ACTIVITY; MYCOBACTERIUM-TUBERCULOSIS; MULTIDRUG-RESISTANT; PULMONARY TUBERCULOSIS; ANTITUBERCULOSIS DRUGS; ETHAMBUTOL RESISTANCE; THERAPY; CYCLOSERINE; AMIKACIN; CAPREOMYCIN;

D O I：

10.1093/cid/cis487

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：572 / 581

页数：10

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