M ethicillin-resistant Staphylococcus aureus (MRSA) remains a preva- lent pathogen in the hospital setting, with an incidence of 25 cases per 1000 inpa- tients, 25% occurring in critical care units. 1 For treatment, vancomycin re- mains a first-line option for invasive MRSA infections such as bacteremia, endocarditis, and pneumonia. 1 Shortcomings of Vancomycin Although vancomycin continues to be a mainstay in MRSA treatment, signifi- cant shortcomings of the therapy have been demonstrated. Vancomycin is a glycopeptide antibiotic that exerts bacte- ricidal activity against most gram-posi- tive organisms (including MRSA) through inhibition of cell wall synthe- sis. 1,2 However, vancomycin has several pharmacokinetic and pharmacodynamic limitations, namely slow bactericidal ac- tivity, poor tissue penetration, reduced Addition of Rifampin to Vancomycin for Methicillin- Resistant Staphylococcus aureus Infections: What Is the Evidence? Simon Tremblay, Tim TY Lau, Mary HH Ensom Infectious Diseases The Annals of Pharmacotherapy ■ 2013 July/August, Volume 47 ■ 1045 theannals.com Author information provided at end of text. © 1967-2013 Harvey Whitney Books Co. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means without prior written permission of Harvey Whitney Books Co. For reprints of any article appearing in The Annals, please contact 415sales@hwbooks.com OBJECTIVE: To evaluate evidence supporting efficacy and safety of the combination of vancomycin and rifampin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. DATA SOURCES: MEDLINE (1946-February 2013), EMBASE (1974-February 2013) and Cochrane Database of Systematic Reviews were searched. STUDY SELECTION: All human prospective trials and retrospective studies evaluating clinical outcomes of vancomycin-rifampin combinations were included. Case reports, case series, and in vitro or animal data were excluded. DATA EXTRACTION: Full-text articles were included and abstracts excluded; 43 of 421 references were reviewed. Five articles met inclusion and were evaluated. DATA SYNTHESIS: A nonrandomized prospective trial reported complete clearance of MRSA bacteremia at 24 hours in all 14 burn patients receiving vancomycin- rifampin therapy. In a case-control study of 42 patients with MRSA endocarditis, adding rifampin prolonged bacteremia (5.2 vs 2.1 days, p < 0.001), decreased survival rates (79% vs 95%, p = 0.048), resulted in drug interactions (52% of cases), and increased hepatic transaminases (21% vs 2%, p = 0.014). In a retrospective analysis of 28 patients with persistent MRSA bacteremia requiring salvage therapy, switching from vancomycin-based to linezolid-based treatment was associated with better salvage success than adding rifampin (88% vs 0%, p < 0.001). In a ran- domized open-label trial of 42 patients with MRSA endocarditis, addition of rifampin to vancomycin did not affect cure rates (90% combination vs 82% monotherapy, p > 0.20), but increased duration of bacteremia (9 vs 7 days, p > 0.20) compared with vancomycin monotherapy. Another randomized open-label trial of combination versus monotherapy for MRSA pneumonia in 93 intensive care unit patients reported higher clinical successes (53.7% vs 31.0%, p = 0.047), similar 30-day mortality rates, and more adverse events with combination therapy (11 vs 6). CONCLUSIONS: Limited evidence exists to support the adjunctive use of rifampin to treat MRSA infections. The combination may increase drug interactions, adverse effects, and rifampin resistance. Further studies are needed to define the role of rifampin adjunct therapy. Ann Pharmacother 2013;47:1045-54. Published Online, 28 May 2013, theannals.com, doi: 10.1345/aph.1R726 by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from