Research Article: Effect of Duration and Intermittency of Rifampin on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis

Date Published: September 15, 2009

Publisher: Public Library of Science

Author(s): Dick Menzies, Andrea Benedetti, Anita Paydar, Ian Martin, Sarah Royce, Madhukar Pai, Andrew Vernon, Christian Lienhardt, William Burman, Megan Murray

Abstract: In a systematic review of randomized controlled trials on tuberculosis treatment, Dick Menzies and colleagues find shorter courses of rifampin to be associated with poorer treatment outcomes.

Partial Text: 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 rifampin-containing regimens could achieve high cure rates with as few as 6 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.

In this review of 57 trials with rifampin-containing regimens, use of rifampin only initially rather than throughout treatment was associated with worse treatment outcomes (higher rates of failure, relapse, and acquired drug resistance). Thrice-weekly intermittent dosing schedules during the initial treatment phase were associated with increased adjusted risk of acquired drug resistance, but not relapse or failure. Initial drug resistance was strongly associated with increased risk of poor treatment outcomes, particularly if rifampin was used only in the initial intensive phase. These findings have important implications for TB treatment.



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