The Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types Among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago [PublishAheadOfPrint]

Cefazolin efficacy with high inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred from an inoculum effect. This study investigated the local prevalence of a cefazolin inoculum effect (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, Illinois contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 hours by broth microdilution method using standard inocula (SI, 5 x 10⁵ CFU/mL) and high inocula (HI, 5 x 10⁷ CFU/mL). The CInE was defined as 1) a ≥ 4-fold increase in C-MIC between SI and HI and/or 2) a pronounced CInE: a nonsusceptible C-MIC of ≥ 16 μg/mL at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate was susceptible to cefazolin at SI and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ-positive, led by gene type C (40%). The CInE was seen in 45 blaZ-positive isolates (23%) with 44 (22%) presenting a ≥ 4-fold increase in C-MIC (SI to HI) and five (3%) with a pronounced CInE. Four out of the five, met both definitions of CInE with two expressing the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

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