Ertapenem and cefazolin combination therapy provided potent in vivo activity against methicillin-susceptible Staphylococcus aureus (MSSA). This activity was beyond what was predicted based on previous in vitro studies, according to study data published in Clinical Infectious Diseases.

The combination therapy was used successfully to salvage 11 MSSA clinical cases, including 6 patients with endocarditis. Patients were identified by the treating physicians; patient data, prior antibiotic history, hematology and chemistry laboratory data, and sources of infection were obtained retrospectively. Before combination salvage therapy, the median duration of bacteremia was 6 days while on antibiotics (range, 4-9 days). In 9 patients in whom  blood cultures were drawn daily, 8 (88%) saw bacteremia cleared within 24 hours. In 2 patients with tricuspid valve endocarditis, bacteremia cleared within 24 hours of therapy initiation in both. “In vitro synergy was modest,” reported investigators, “however, cefazolin plus ertapenem did exhibit synergistic action in a rat model of MSSA endocarditis as well.”

“Cefazolin plus ertapenem combination salvage therapy resulted in rapid MSSA bacteremia clearance in patients failing standard monotherapy, even in cases with large-burden endovascular infections on echocardiogram,” according to investigators. They also noted the considerable discordance between in vitro synergy testing by the disk diffusion, checkerboard, and time-kill assays raises questions as to how clinically relevant results of these assays are in assessing the apparent strong synergy of the antibiotics in vivo and in rat models. “Based on these cumulative results, cefazolin plus ertapenem appears to offer a viable salvage regimen option in patients with MSSA bacteremia refractory to standard β-lactam therapy, provided appropriate surgical source control has been performed,” said investigators.

Disclosure: A study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.


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Reference

Ulloa ER, Singh KV, Geriak M, et al. Cefazolin and ertapenem salvage therapy rapidly clears persistent methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis. 2020;71(6):1413-8. doi:10.1093/cid/ciz995.