Addition of rifampin to standard therapy for treatment of native valve infective endocarditis caused by Staphylococcus aureus

Staphylococcus aureus is a common cause of native valve infective endocarditis (IE). Rifampin is often added to traditional therapy for the management of serious S. aureus infections. There are no large, prospective studies documenting the safety and efficacy of adjunctive therapy with rifampin for treatment of native valve S. aureus IE. We reviewed all cases of definite native valve S. aureus IE confirmed by modified Duke criteria in a large urban hospital between 1 January 2004 and 31 December 2005. A retrospective cohort analysis was used to assess the impact of the addition of rifampin to standard therapy. There were 42 cases of S. aureus IE treated with the addition of rifampin and 42 controls. Cases received a median of 20 days of rifampin (range, 14 to 48 days). Rifampin-resistant S. aureus isolates developed in nine cases who received rifampin before clearance of bacteremia (56%), while significant hepatic transaminase elevations also occurred in nine cases, all of whom had hepatitis C infection. Unrecognized significant drug-drug interactions with rifampin occurred frequently (52%). Cases were more likely to have a longer duration of bacteremia (5.2 versus 2.1 days; P < 0.001) and were less likely to survive (79% versus 95%; P = 0.048) than controls. Our results suggest that the potential for hepatotoxicity, drug-drug interactions, and the emergence of resistant S. aureus isolates warrants a careful risk-benefit assessment before adding rifampin to standard antibiotic treatment of native valve S. aureus IE until further clinical studies are performed.