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

Autor: Paul Daru, Hans L. Rieder, Salim Ah, Armand Van Deun, Pankaj Kumar Das, Mihir Ranjan Sarker, Aung Kya Jai Maug
Přispěvatelé: University of Zurich, Van Deun, A
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Male
Antitubercular Agents
Effectiveness
Kaplan-Meier Estimate
Multidrug resistance
Critical Care and Intensive Care Medicine
Gatifloxacin
Clofazimine
Cohort Studies
Kanamycin
Tuberculosis
Multidrug-Resistant
Prospective Studies
Bangladesh
Anti-Inflammatory Agents
Non-Steroidal
Middle Aged
Anti-Bacterial Agents
Treatment Outcome
Drug Therapy
Combination
Female
Asia
South
Delamanid
2706 Critical Care and Intensive Care Medicine
Ethambutol
Regimens
medicine.drug
Pulmonary and Respiratory Medicine
Adult
medicine.medical_specialty
Tuberculosis
Bacterial diseases
610 Medicine & health
Young Adult
Pharmacotherapy
Internal medicine
Intensive care
Isoniazid
medicine
Humans
Intensive care medicine
Tuberculosis
Pulmonary
business.industry
Mycobacterium tuberculosis
10060 Epidemiology
Biostatistics and Prevention Institute (EBPI)
Pyrazinamide
medicine.disease
Standardization
Regimen
2740 Pulmonary and Respiratory Medicine
Prothionamide
Cost-effectiveness
business
Relapses
Popis: 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
Databáze: OpenAIRE
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