Combination of ertapenem and penicillin M or cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: multicenter case series

• In several hospital centers, a combination of an anti-staphylococcal β-lactam with ertapenem has been used in treatment of persistent methicillin-sensitive Staphylococcus aureus bacteremia. • Due to the time required to obtain conclusive blood culture results, 40% of patients receiving dual therapy ultimately had negative blood cultures prior to its initiation • The aforementioned antibiotic combinations may raise tolerability concerns and are liable to induce severe encephalopathy. • Although the effectiveness of this dual therapy appears promising, applicable indications remain to be defined. Dual therapy (DT) combining penicillin M or cefazolin with ertapenem has been proposed as treatment of complicated Staphylococcus aureus bacteremia (SAB). We aimed to outline the relevant clinical characteristics and outcomes in real-life practice . We conducted a multicenter retrospective study involving SAB cases treated by means of DT in five French university hospitals between January 2022 and December 2024. Thirty-five patients were included, all of them suffering from complicated SAB. Although DT was prescribed for persistent bacteremia, due to protracted blood culture incubation, at the time when DT was finally initiated, only 21 patients (60%) had positive blood cultures,. Median bacteremia duration after DT was two days (IQR 1–3). Two serious adverse events (5.7%), both having to do with to encephalopathy, were reported. Seven patients (20%) died, five on account of SAB. Due to the time taken to obtain usable blood culture, 40% of the patients had already cleared bacteremia before DT could be initiated. Further studies are needed to better define the role of this strategy and to identify the patients most likely to benefit.