Short, highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis

A Van Deun, AK Maug, MA Salim, PK Das, MR Sarker, P Daru, HL Rieder

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    RATIONALE: Based on expert opinion, the global guidelines for management of multidrug-resistant tuberculosis impose lengthy and often poorly tolerated treatments. OBJECTIVES: This observational study evaluates the effectiveness of standardized regimens for patients with proven multidrug-resistant tuberculosis previously untreated with second-line drugs in low-income countries. METHODS: Consenting patients were sequentially assigned to one of six standardized treatment regimens. Subsequent cohorts were treated with regimens adapted according to results in prior cohorts, striving to minimize failure and default, while reducing total treatment duration without increasing relapse frequency. Measurements and results: We report the treatment outcome of all patients with laboratory-confirmed multidrug-resistant tuberculosis enrolled from May 1997 to December 2007. The final most effective treatment regimen required a minimum of nine months duration with gatifloxacin, clofazimine, ethambutol, and pyrazinamide throughout, supplemented by prothionamide, kanamycin, and high-dose isoniazid during an intensive phase of a minimum of four months, giving a relapse-free cure of 87.9% (95% confidence interval 82.7% to 91.6%) among 206 patients. Major adverse drug reactions were infrequent and manageable. Compared to the 221 patients treated with regimens based on ofloxacin and commonly prothionamide throughout, the hazard ratio of any adverse outcome was 0.39 (95% confidence interval 0.26-0.59). CONCLUSIONS: Serial regimen formulation guided by overall treatment effectiveness ultimately resulted in treatment outcomes comparable to those obtained with first-line treatment. Confirmatory formal trials in populations with high levels of human immunodeficiency virus co-infection and in populations with a higher initial prevalence of resistance to second-line drugs are required
    Original languageEnglish
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume182
    Issue number5
    Pages (from-to)684-692
    Number of pages9
    ISSN1073-449X
    DOIs
    Publication statusPublished - 2010

    Keywords

    • B780-tropical-medicine
    • Bacterial diseases
    • Tuberculosis
    • Mycobacterium tuberculosis
    • Multidrug resistance
    • Standardization
    • Regimens
    • Effectiveness
    • Cost-effectiveness
    • Treatment outcome
    • Gatifloxacin
    • Clofazimine
    • Ethambutol
    • Pyrazinamide
    • Prothionamide
    • Kanamycin
    • Isoniazid
    • Relapses
    • Bangladesh
    • Asia-South

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