Successful Treatment of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Bacteremia with the Addition of Rifampin to Daptomycin

OBJECTIVE: To report a case in which daptomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was successfully treated with the addition of rifampin to daptomycin. CASE SUMMARY: An 84-year-old male presented with fever and chills following cystoscopy. After culturing was conducted, the patient received single doses of vancomycin and gentamicin and then continued on vancomycin plus ceftazidime. Blood cultures grew MRSA, with vancomycin and daptomycin minimum inhibitory concentrations (MICs) of <= 1 mu g/mL and 0.25 mu g/mL, respectively. Vancomycin was continued, with trough concentrations maintained >15 mu g/mL, but results of blood cultures remained positive. On day 10, therapy was switched to daptomycin 6 mg/kg/day, but culture results remained positive. On day 13, testing for vancomycin heteroresistance was negative, with the MIC unchanged. The vancomycin MIC remained unchanged on day 19, but the daptomycin MIC had increased to 2 mu g/mL. Rifampin 300 mg orally twice daily was added on day 20; blood cultures obtained 2 days later were sterile. The patient was discharged to complete a 6-week course of antibiotics and was doing well 4 months following therapy. DISCUSSION: Analysis of MRSA isolates obtained on days 1 and 19 showed an increase in the daptomycin MIC from 0.25 to 2 mu g/mL. Because intervening isolates were not available for susceptibility testing, it is not possible to associate this increase with exposure to either vancomycin or daptomycin. Although in vitro synergy was not seen in this case, addition of rifampin to daptomycin therapy resolved the bacteremia. CONCLUSIONS: In patients with persistent MRSA bacteremia, isolates should be retested for susceptibility to both daptomycin and vancomycin, including assessment for vancomycin heteroresistance. Addition of rifampin to daptomycin may be effective for persistent MRSA bacteremia, even if daptomycin MICs are elevated. Prospective studies are needed to define the role of combination therapy.