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

Menzies, Dick; Benedetti, Andrea; Paydar, Anita; Martin, I.C.; Royce, Sarah; Pai, Madhukar; Vernon, Andrew; Lienhardt, Christian; Burman, William J.

doi:10.1371/journal.pmed.1000146

Cited by 182 publications

(152 citation statements)

References 58 publications

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“…Two studies which compared the use of RIF to the use of ethambutol (ETB) in the continuation phase after initial treatment with isoniazid (INH)-RIF-pyrazinamide (PZA)-ETB found that those on ETB-INH were 2 to 3 times more likely to experience treatment failure or TB relapse than those on RIF-INH for continuation therapy (135,204). Several meta-analyses have shown that treatment with a longer duration (6 months or longer) of a rifamycin drug (rifampin or rifabutin [RfB]) resulted in lower rates of failure and recurrence and improved survival during treatment, compared to only 2 months of treatment with a rifamycin drug (146,150,186). More recent data suggest that a duration of rifampin treatment even longer than the recommended 6 months may decrease failure and recurrence rates even further (146,239).…”

Section: Treatment Of Tb For Hiv-infected Patients: Rifampin Combinatmentioning

confidence: 99%

HIV and Tuberculosis: a Deadly Human Syndemic

2011

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SUMMARY A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.

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Section: Treatment Of Tb For Hiv-infected Patients: Rifampin Combinatmentioning

confidence: 99%

HIV and Tuberculosis: a Deadly Human Syndemic

2011

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“…Clinical data for the impact of drug pressure on de novo drug resistance evolution stem mostly from infections requiring long-lasting treatment such as HIV [32][33][34] and TB [35]. For HIV-1, studies considering resistance evolution in relation to patient adherence suggest that treatment that does not completely suppress pathogen replication facilitates de novo evolution of resistance [32 -34,36].…”

Section: Empirical Evidencementioning

confidence: 99%

The path of least resistance: aggressive or moderate treatment?

et al. 2014

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The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution.

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“…There is concern that the development of acquired rifamycin monoresistance (ARR), treatment failure, and relapse may be associated with intermittent dosing (4,20), insufficient companion drug exposure (33), or low rifamycin concentrations (9,21). RFP's sterilizing effect has been shown to be dose dependent in murine studies which suggest that daily doses of RFP may reduce treatment duration to just 3 months (25,26,37), and higher doses of RFP are associated with improved early bactericidal activity in humans (29).…”

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confidence: 99%

Effects of Four Different Meal Types on the Population Pharmacokinetics of Single-Dose Rifapentine in Healthy Male Volunteers

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Walt

Smith

et al. 2010

Antimicrob Agents Chemother

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Rifapentine and its primary metabolite, 25-desacetyl rifapentine, are active against mycobacterium tuberculosis. The objectives of this study were to describe the population pharmacokinetics of rifapentine and 25-desacetyl rifapentine in fasting and fed states. Thirty-five male healthy volunteers were enrolled in an open-label, randomized, sequential, five-way crossover study. Participants received a single 900-mg dose of rifapentine after meals with high fat (meal A), bulk and low fat (meal B), bulk and high fat (meal C), high fluid and low fat (meal D), or 200 ml of water (meal E). Venous blood samples were collected over 72 h after each rifapentine dose, and plasma was analyzed for rifapentine and 25-desacetyl rifapentine using high-performance liquid chromatography. Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM. Compared with the fasting state, meal A had the greatest effect on rifapentine oral bioavailability, increasing it by 86%. Meals B, C, and D resulted in 33%, 46%, and 49% increases in rifapentine oral bioavailability, respectively. Similar trends were observed for 25-desacetyl rifapentine. As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches.Rifapentine (RFP), a cyclopentyl rifamycin, is an orally administered drug registered by the Food and Drug Administration (FDA) for the treatment of pulmonary tuberculosis (TB). It exerts its antibacterial activity through inhibition of DNAdependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis (32). RFP has a microbiologically active metabolite, 25-desacetyl rifapentine (25-DRFP) (10). RFP has a long half-life (5, 17) and superior in vitro potency against M. tuberculosis in comparison with rifampin and rifabutin (10), making it an attractive candidate for shortening and simplifying antitubercular therapy.Currently, RFP is dosed at 600 mg either once weekly or twice weekly in human immunodeficiency virus (HIV)-negative patients with noncavitary TB (2). There is concern that the development of acquired rifamycin monoresistance (ARR), treatment failure, and relapse may be associated with intermittent dosing (4, 20), insufficient companion drug exposure (33), or low rifamycin concentrations (9, 21). RFP's sterilizing effect has been shown to be dose dependent in murine studies which suggest that daily doses of RFP may reduce treatment duration to just 3 months (25,26,37), and higher doses of RFP are associated with improved early bactericidal activity in humans (29). Clinical trials are currently evaluating new antituberculosis regimens containing higher doses of RFP used intermittently or daily doses of RFP. Concomitant food has a marked effect on RFP absorption (6). The effect of food on systemic RFP exposure may therefore impact treatment activity and safety. The aim of this study was to investigate the effect of meals differing in fat and bulk content on the rate and extent of RFP absorption and 25-DRFP disposition. The ...

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

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.

Cited by 182 publications

References 58 publications

HIV and Tuberculosis: a Deadly Human Syndemic

HIV and Tuberculosis: a Deadly Human Syndemic

The path of least resistance: aggressive or moderate treatment?

Effects of Four Different Meal Types on the Population Pharmacokinetics of Single-Dose Rifapentine in Healthy Male Volunteers

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