Addition of Rifampin to Vancomycin for Methicillin-Resistant Staphylococcus aureus Infections: What Is the Evidence?

Abstract

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 randomized 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.