Clinical Impact of the Cefazolin Inoculum Effect

The project will investigate the clinical impact of the cefazolin inoculum effect (CzIE) in deep-seated MSSA infections, defined as a cefazolin minimal inhibitory concentration of > 16 µg/ml when a high inoculum (10^7 CFU/ml) is used. It will also determine the clinical value and feasibility of a novel colorimetric nitrocefin-based rapid test (~3 h) for detecting CzIE, which has shown high sensitivity and specificity. The research will leverage the Staphylococcus aureus Network Adaptive Platform (SNAP) trial, a multicenter, pragmatic, multi-arm, open-label adaptive platform trial, focusing on the MSSA "domain" that evaluates cefazolin vs isoxazolyl-penicillins. The specific aims are to define the clinical impact of CzIE in MSSA bacteremia and to determine the clinical value and feasibility of the rapid test for CzIE detection.