The Efficacy of Cefazolin and Ertapenem combination treatment for Persistent MSSA Bacteraemia: A ten-year multicentre retrospective cohort study.
- 1The Prince Charles Hospital
Abstract
Objectives Persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is associated with significant morbidity and mortality. Cefazolin-ertapenem combination therapy has demonstrated synergistic activity in preclinical models and small case series, but comparative clinical evidence is lacking. Methods We conducted a multicentre retrospective review of all patients aged >18 years with persistent MSSA bacteraemia at two Queensland tertiary hospitals between January 2014 and December 2024. The primary outcome was time to blood culture sterilisation, compared between patients who commenced cefazolin-ertapenem combination therapy prior to first negative blood culture and a matched cohort of non-combination-treated patients. Secondary outcomes included 90-day all-cause mortality, 90-day relapse, development of multi-resistant organisms, Clostridioides difficile infection, and adverse drug events. Results A total of 288 episodes of persistent MSSA bacteraemia in 283 patients were identified. Twenty-six patients received cefazolin-ertapenem combination therapy. Among the 14 patients who commenced combination therapy prior to first negative blood culture, median time to sterilisation was 1 day (IQR 1 - 2), compared with 2 days (IQR 1 - 3) in the matched non-combination group. Cox regression in the matched cohort (n=114) demonstrated an increased rate of blood culture clearance with combination therapy (HR 1.8; 95% CI 1.2 - 2.7; P =0.004). In the full cohort, ninety-day mortality (20.0% vs 23.0%, P=0.73) and relapse rates (11.5% vs 8.3%, P =0.57) did not differ significantly between groups. Conclusions Cefazolin-ertapenem combination therapy was associated with accelerated blood culture sterilisation in persistent MSSA bacteraemia. Prospective randomised evaluation is warranted.
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BibTeX
@misc{lane2026efficacy,
title = {{The Efficacy of Cefazolin and Ertapenem combination treatment for Persistent MSSA Bacteraemia: A ten-year multicentre retrospective cohort study.}},
author = {A. Lane and K. Hay and S. Sivakumaran and H. Dolby and S. Winlaw and D. Wise and V. Muruganandah and S. Heraganahally and N.-I. Lalwani and M. Eustace and F. Chui and T. Kelly and A. Redmond and P. R. Chapman and A. Chaudhuri and K. Vemuri and A. Burke and J. McNamara and B. E. Barber and R. Horvath},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.26367257},
url = {https://www.medrxiv.org/content/10.64898/2026.11.04.26367257v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The Efficacy of Cefazolin and Ertapenem combination treatment for Persistent MSSA Bacteraemia: A ten-year multicentre retrospective cohort study.
AU - A. Lane
AU - K. Hay
AU - S. Sivakumaran
AU - H. Dolby
AU - S. Winlaw
AU - D. Wise
AU - V. Muruganandah
AU - S. Heraganahally
AU - N.-I. Lalwani
AU - M. Eustace
AU - F. Chui
AU - T. Kelly
AU - A. Redmond
AU - P. R. Chapman
AU - A. Chaudhuri
AU - K. Vemuri
AU - A. Burke
AU - J. McNamara
AU - B. E. Barber
AU - R. Horvath
PY - 2026
DA - 2026/11/04
PB - medRxiv
DO - 10.64898/2026.11.04.26367257
UR - https://www.medrxiv.org/content/10.64898/2026.11.04.26367257v1
AB - Objectives Persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is associated with significant morbidity and mortality. Cefazolin-ertapenem combination therapy has demonstrated synergistic activity in preclinical models and small case series, but comparative clinical evidence is lacking. Methods We conducted a multicentre retrospective review of all patients aged >18 years with persistent MSSA bacteraemia at two Queensland tertiary hospitals between January 2014 and December 2024. The primary outcome was time to blood culture sterilisation, compared between patients who commenced cefazolin-ertapenem combination therapy prior to first negative blood culture and a matched cohort of non-combination-treated patients. Secondary outcomes included 90-day all-cause mortality, 90-day relapse, development of multi-resistant organisms, Clostridioides difficile infection, and adverse drug events. Results A total of 288 episodes of persistent MSSA bacteraemia in 283 patients were identified. Twenty-six patients received cefazolin-ertapenem combination therapy. Among the 14 patients who commenced combination therapy prior to first negative blood culture, median time to sterilisation was 1 day (IQR 1 - 2), compared with 2 days (IQR 1 - 3) in the matched non-combination group. Cox regression in the matched cohort (n=114) demonstrated an increased rate of blood culture clearance with combination therapy (HR 1.8; 95% CI 1.2 - 2.7; P =0.004). In the full cohort, ninety-day mortality (20.0% vs 23.0%, P=0.73) and relapse rates (11.5% vs 8.3%, P =0.57) did not differ significantly between groups. Conclusions Cefazolin-ertapenem combination therapy was associated with accelerated blood culture sterilisation in persistent MSSA bacteraemia. Prospective randomised evaluation is warranted.
ER -