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Free Content Intermittent tuberculosis treatment for patients with isoniazid intolerance or drug resistance

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Twenty tuberculosis (TB) clinics in the United States and Canada.


To evaluate the efficacy and safety of a 6-month intermittent regimen of rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB) in human immunodeficiency virus (HIV) negative patients with culture-confirmed pulmonary or extra-pulmonary tuberculosis and either isoniazid (INH) resistance or INH intolerance.


Patients were enrolled in a single-arm clinical trial to receive intermittent dosing after at least 14 initial daily doses of RMP+PZA+EMB. Treatment was continued twice (BIW) or thrice weekly (TIW) per physician/patient preference for a total of 6 months, with 2 years of follow-up for relapse after treatment.


From 1999 to 2004, 98 patients were enrolled, 78 with reported INH resistance and 20 with INH intolerance. BIW dosing was used in 77 and TIW in 21. Study treatment was completed in 73 (74%). Reasons for discontinuation were hepatic adverse events (n= 12), other adverse effects (n= 3) and other reasons (n= 10). Failure (n= 1) and relapse (n= 2) occurred in 3 (3.5%, 95%CI 1.2–9.8) of 86 patients eligible for efficacy analysis, all occurring in patients with cavitary, acid-fast bacilli smear-positive pulmonary TB.


Intermittent RMP+PZA+EMB appears to be effective in HIV-negative patients, but the regimen is poorly tolerated, possibly due to the prolonged use of PZA. Alternative regimens of lower toxicity are needed.

Keywords: anti-tuberculosis agents; mycobacterial infections; tuberculosis

Document Type: Research Article


Affiliations: 1: Denver Public Health Department, Denver, Colorado, USA 2: Centers for Disease Control and Prevention, Atlanta, Georgia, USA 3: Family Health International 360, Durham, North Carolina, USA 4: University of Washington, Seattle, Washington, USA 5: South Texas-Audie Murphy VA Hospital Research Collaboration, Harlingen, Texas, USA 6: University of Manitoba, Winnipeg, Manitoba, Canada

Publication date: May 1, 2014

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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