Follow-up Outcomes of Cefazolin Usage vs. Standard therapy in Infective Endocarditis (FOCUS-IE): A substudy of the SNAP MSSA Domain

• Methicillin susceptible Staphylococcus aureus (MSSA) remains one of the most common causes of infective endocarditis (IE), with an in-hospital mortality rate of ~30% even with oprimal medical therapy.
• Most guidelines continue to favour anti-staphylococcal penicillins (ASP) such as (flu)cloxacillin largely due to concerns of cefazolin's inability to overcome the inoculum effect demonstrated in in-vitro studies. However, these concerns are largely theoretical.
• The SNAP trial has now generated evidence for the use of cefazolin vs. (flu)cloxacillin in patients with MSSA. Given that endocarditis represents a clinically relevant high-inoculum infection state in which ASPs may theoretically outperform cefazolin, a dedicated subgroup analysis of SNAP patients with IE is both biologically and clinically essential.
• This study aims to determine whether cefazolin is non-inferior to (flu)cloxacillin with respect to 90-day mortality, among SNAP participants with MSSA IE.