Prevalence of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus Isolates Collected from Kingston Health Sciences Centre.

Background: Staphylococcus aureus is a bacterium that causes serious human infections, including bloodstream infections, pneumonia, deep abscesses, and bone and joint infections. Methicillin-susceptible S. aureus (MSSA) are S. aureus bacteria susceptible to the antibiotic methicillin. Cefazolin is the first-line antibiotic to treat MSSA infections. The cefazolin inoculum effect (CzIE) is a lab phenomenon in which S. aureus is susceptible to cefazolin at a standard bacterial inoculum but develops resistance at a higher cell inoculum. CzIE occurs when the bacteria produce beta-lactamases that degrade cefazolin, preventing the antibiotic from inhibiting cell wall synthesis and allowing bacterial growth. In theory, CzIE may lead to cefazolin treatment failure, but currently, there is insufficient evidence in the literature. Objective: We aimed to determine the prevalence of the CzIE in patients with serious MSSA infections at Kingston Health Sciences Centre (KHSC). Methods: Clinical MSSA isolates from patients with serious infections at KHSC were collected. The MSSA isolates were then tested for CzIE using broth microdilution testing at a standard inoculum (5×10^5 CFU/mL) and a high inoculum (5×10^7 CFU/mL). The CzIE was defined as a ≥ 4-fold increase in minimum inhibitory concentration (MIC) from the standard to the high and with a MIC above the resistant breakpoint of 16 µg/mL. Results: Of the 51 MSSA isolates tested to date, 17 (33%) displayed CzIE, with 13 of the 17 (76%) requiring 64 µg/ml of antibiotic to prevent growth. Conclusion: Our initial testing indicates that the CzIE is common in MSSA infections at KHSC. We will complete testing 100 MSSA isolates for a more precise estimate of CzIE prevalence, which will be followed up with a chart review of the patients to determine if there is a correlation between CzIE and cefazolin treatment failure.