2026 Southeastern Residency Conference

Comparison of cefazolin plus ertapenem to alternative approaches in patients with persistent MSSA bacteremia while on cefazolin
Natalie Harris, PharmD1; Caroline Jozefczyk, PharmD, BCIDP2; Jake Crocker, PharmD, BCIDP2; Sarah Al Mansi, MD1; Brandon Bookstaver, PharmD, BCIDP1,3

• Prisma Health Richland Hospital, Columbia, SC
• Prisma Health Greenville Memorial Hospital, Greenville, SC
• University of South Carolina College of Pharmacy, Columbia, SC

Background: Persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia despite standard cefazolin therapy poses a significant clinical challenge. Historically, salvage approaches have involved anti-staphylococcal penicillins (ASPs), given the growing concern for cefazolin inoculum effect. With ASPs less favorable pharmacokinetic and safety profile, various combination regimens have emerged as potential alternatives. Data directly comparing salvage strategies remains limited. This study compared outcomes of cefazolin plus ertapenem versus alternative salvage therapies in persistent MSSA bacteremia.
Methods: This retrospective cohort study included adults who failed cefazolin and received salvage therapy for persistent MSSA bacteremia from March 1, 2021 to August 31, 2025. Patients were excluded if they transferred from another hospital, had polymicrobial bacteremia, died within 24 hours, or received empiric therapy for > 24 hours after positive blood cultures. The primary objective was to compare the duration of MSSA bacteremia after salvage therapy in patients receiving cefazolin plus ertapenem versus alternative salvage strategies. Secondary objectives included all-cause mortality, infection related re-admission, and adverse effects (ADEs) in both groups.
Results: Fifty-seven patients were included, with 30 in the cefazolin plus ertapenem cohort and 27 in the alternative cohort. The most common source was skin and soft tissue (n=19, 33.3%), and endocarditis was the most common complication (n=17, 29.8%). Most patients in the alternative salvage cohort received nafcillin (n/N=19/30, 70.4%). The average duration of bacteremia after salvage was 1.6 and 2.8 days in the cefazolin plus ertapenem and alternative cohorts, respectively. Patients receiving cefazolin plus ertapenem experienced higher rates of 90-day mortality (23.3% vs 22.2%) and infection-related re-admission (26.7% vs 11.1%), however, patients receiving alternative salvage therapy experienced more ADEs (51.9% vs 36.7%).
Conclusion: Cefazolin plus ertapenem shortened bacteremia duration and led to less ADEs compared with alternative regimens, supporting the use of this combination as a salvage therapy option in persistent MSSA bacteremia.