Cefazolin and Ertapenem Salvage Therapy Rapidly Clears Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia

Abstract

Cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases. While in vitro synergy was modest, cefazolin plus ertapenem exhibited synergistic action in a rat model of MSSA endocarditis. The combination of cefazolin and ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis.

Keywords: Staphylococcus aureus; bacteremia; cefazolin; endocarditis; ertapenem.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Efficacy of antibiotic therapy in a rat endocarditis model of infection with methicillin-susceptible Staphylococcus aureus TX0117. The results of therapy with cefazolin, ertapenem, and cefazolin-ertapenem for TX0117-infected rats are shown. Horizontal bars represent the geometric mean colony-forming unit titers. No antibiotics, filled circles; cefazolin, filled asterisks; ertapenem, open diamonds; cefazolin + ertapenem, closed diamonds. *P < .05, by 2-tailed Mann-Whitney test. **P = .005, ****P < .0001, by Kruskal-Wallis 1-way analysis of variance. Abbreviations: abx, antibiotics; CFU, colony-forming units; CZ, cefazolin; ETP, ertapenem; ns, not significant.