Document Detail

4 months of rifampin compared with 9 months of isoniazid for the management of latent tuberculosis infection: a meta-analysis and cost-effectiveness study that focuses on compliance and liver toxicity.
MedLine Citation:
PMID:  19911936     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: One-third of the world's population is infected with tuberculosis, and 9 months of isoniazid monotherapy is the treatment of choice for latent tuberculosis infection. However, this approach has been associated with hepatotoxicity and poor compliance. A shorter (4-month) rifampin regimen has been evaluated in recent clinical trials. METHODS: We performed a meta-analysis of the published studies to compare compliance, toxicity, and cost-effectiveness between the 2 strategies. Pooled effects were calculated as risk ratios (RRs) by means of random-effects and fixed-effects models. RESULTS: Pooled data from 3586 patients suggested that 4-month rifampin therapy was associated with a significant reduction in the risk of noncompletion (RR for random-effects model, 0.53; 95% confidence interval [CI], 0.44-0.63). Noncompletion rates were lower among patients who received 4-month rifampin therapy (range, 8.6%-28.4%), compared with noncompletion rates among patients who received 9-month isoniazid therapy (range, 24.1%-47.4%). Also, rates of hepatotoxicity (defined as grade 3 or 4 liver failure leading to drug discontinuation) were lower for patients who received 4-month rifampin therapy (range, 0%-0.7%), compared with the corresponding rates for patients who received 9-month isoniazid therapy (range, 1.4%-5.2%), and rifampin was associated with significant reduction in the risk of hepatotoxicity (RR for fixed-effects model, 0.12; 95% CI, 0.05-0.30). Notably, with the data from our meta-analysis, we calculated that the 4-month rifampin strategy is also cost-effective and results in $213 savings per patient treated ($90/patient when doctor fees are not included). CONCLUSIONS: The improved compliance, safety, and cost associated with the 4-month rifampin therapy suggest that the efficacy of this approach needs to be evaluated in detail. An extended posttreatment follow-up in future studies will clarify the unresolved issue of tuberculosis reactivation rates.
Panayiotis D Ziakas; Eleftherios Mylonakis
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Publication Detail:
Type:  Comparative Study; Journal Article; Meta-Analysis    
Journal Detail:
Title:  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America     Volume:  49     ISSN:  1537-6591     ISO Abbreviation:  Clin. Infect. Dis.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2010-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9203213     Medline TA:  Clin Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1883-9     Citation Subset:  IM    
Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-2696, USA.
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MeSH Terms
Antitubercular Agents / therapeutic use*
Cost-Benefit Analysis
Health Care Costs
Isoniazid / adverse effects,  economics,  therapeutic use*
Liver / drug effects*
Medication Adherence*
Rifampin / adverse effects,  economics,  therapeutic use*
Tuberculosis / drug therapy*
Reg. No./Substance:
0/Antitubercular Agents; 13292-46-1/Rifampin; 54-85-3/Isoniazid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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