Impact of hypoalbuminemia on patients receiving ertapenem combination therapy for methicillin-susceptible Staphylococcus aureus bacteraemia

Abstract Background Ertapenem combination therapy has been associated with a faster time to blood culture sterilization in patients with MSSA bacteraemia. However, guidance documents advise avoiding ertapenem in patients with a serum albumin level of <2.5 g/dL for Gram negative infections given that ertapenem is highly protein bound and patients with hypoalbuminemia may experience suboptimal ertapenem exposures. Patients and methods This study was a retrospective, multicenter study of consecutive adult patients with MSSA bacteraemia for >48 h who were treated with cefazolin, oxacillin, or nafcillin in combination with ertapenem. Patients with hypoalbuminemia, defined as a serum albumin level of <2.5 g/dL, were compared to those with normal albumin levels. Patients received ertapenem 1 g every 24 h or 500 mg every 24 h if they had a creatinine clearance below 30 mL/min. The primary outcome was time from ertapenem administration to negative blood cultures. Results Among the 109 patients who received ertapenem for MSSA bacteraemia, 100 met the inclusion criteria. Thirty-eight percent were patients who inject drugs and 52% had definitive endocarditis. After propensity score weighting, patients with hypoalbuminemia had a significantly longer time to negative blood cultures compared to patients with normal albumin levels (HR=0.45, 95% CI: 0.27–0.72, P = 0.001). Conclusions Among patients with persistent MSSA bacteraemia who were treated with ertapenem combination therapy, patients with hypoalbuminemia had a significantly longer time to negative blood cultures. Pharmacokinetic studies are warranted to confirm if these findings are due to drug exposures or the underlying condition of patients with hypoalbuminemia.