2025/05/31 by Sunish Shah, Lloyd Clarke, G.K. Balasubramani +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Antibiotic Resistance in Bacteria #Antibiotics Pharmacokinetics and Efficacy #Antimicrobial Resistance in Staphylococcus
paper · doi:10.1093/jac/dkaf134
openalex publication_date 2025/05/31 · openalex created_date 2025/06/01 · openalex updated_date 2026/07/26
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.