Abstract
Treatment regimens for active tuberculosis (TB) that are intermittent, or use rifampin during only the initial phase, offer practical advantages, but their efficacy has been questioned. We conducted a systematic review of treatment regimens for active TB, to assess the effect of duration and intermittency of rifampin use on TB treatment outcomes. PubMed, Embase, and the Cochrane CENTRAL database for clinical trials were searched for randomized controlled trials, published in English, French, or Spanish, between 1965 and June 2008. Selected studies utilized standardized treatment with rifampin-containing regimens. Studies reported bacteriologically confirmed failure and/or relapse in previously untreated patients with bacteriologically confirmed pulmonary TB. Pooled cumulative incidences of treatment outcomes and association with risk factors were computed with stratified random effects meta-analyses. Meta-regression was performed using a negative binomial regression model. A total of 57 trials with 312 arms and 21,472 participants were included in the analysis. Regimens utilizing rifampin only for the first 1-2 mo had significantly higher rates of failure, relapse, and acquired drug resistance, as compared to regimens that used rifampin for 6 mo. This was particularly evident when there was initial drug resistance to isoniazid, streptomycin, or both. On the other hand, there was little evidence of difference in failure or relapse with daily or intermittent schedules of treatment administration, although there was insufficient published evidence of the efficacy of twice-weekly rifampin administration throughout therapy. TB treatment outcomes were significantly worse with shorter duration of rifampin, or with initial drug resistance to isoniazid and/or streptomycin. Treatment outcomes were similar with all intermittent schedules evaluated, but there is insufficient evidence to support administration of treatment twice weekly throughout therapy.
Highlights
When rifampin was first introduced, it held the promise of exceptional potency as an agent for treatment of Mycobacterium tuberculosis
A series of randomized trials, most conducted 20–35 y ago, established that rifampincontaining regimens could achieve high cure rates with as few as mo of therapy, even when given intermittently [1]. These trials ushered in the modern era of short-course chemotherapy and established the scientific rationale for the standardized regimens currently recommended by the World Health Organization (WHO) [2]
WHO recommends direct observation of all doses of rifampin to prevent rifampin resistance, which is associated with much worse treatment outcomes, especially when combined with isoniazid resistance as multi-drug resistance (MDR) [3,4]
Summary
When rifampin was first introduced, it held the promise of exceptional potency as an agent for treatment of Mycobacterium tuberculosis (the cause of tuberculosis [TB]). A series of randomized trials, most conducted 20–35 y ago, established that rifampincontaining regimens could achieve high cure rates with as few as mo of therapy, even when given intermittently [1] These trials ushered in the modern era of short-course chemotherapy and established the scientific rationale for the standardized regimens currently recommended by the World Health Organization (WHO) [2]. WHO recommends direct observation of all doses of rifampin to prevent rifampin resistance, which is associated with much worse treatment outcomes, especially when combined with isoniazid resistance as multi-drug resistance (MDR) [3,4] This direct observation is facilitated by shorter duration of rifampin, and/or by intermittent dosing schedules. Tuberculosis—a contagious infection, usually of the lungs—kills nearly two million people annually It is caused by Mycobacterium tuberculosis, bacteria that are spread in airborne droplets when people with tuberculosis cough.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call