Association Between the blaZ Gene and the Cefazolin Inoculum Effect among Bloodstream Isolates of Methicillin-Susceptible Staphylococcus aureus

• A 12.4% prevalence of cefazolin inoculum effect (CzIE) was found among MSSA bloodstream isolates in Hangzhou. • The blaZ type A genotype is strongly associated with CzIE, showing a positivity rate of 42.9%. • Standardized MIC testing combined with sequencing reliably linked genotype to phenotype. Investigating the incidence of the cefazolin inoculum effect (CzIE) in methicillin-susceptible Staphylococcus aureus and its correlation with the blaZ gene. Genotyping and blaZ gene detection using Sanger sequencing were conducted on 113 MSSA isolates from bloodstream infections at a tertiary hospital in Hangzhou, Zhejiang Province, collected from January 2021 to October 2024. Cefazolin susceptibility was determined using the broth microdilution method under standard (5 × 10 5 CFU/mL) and high (5 × 10 7 CFU/mL) inoculum conditions. Statistical analysis was performed using SPSS Statistics 29.0. Among the 113 MSSA strains, 94 carried the blaZ gene, with the highest proportion being type C (57/94, 60.6%), followed by type A (21/94, 22.4%), type B (16/94, 17.0%), and no type D was detected. The overall CzIE prevalence was 12.4% (14/113). blaZ type A isolates exhibited a significantly higher CzIE rate (42.9%, 9/21) compared to type B (0%, 0/16) and type C (9.8%, 5/57) (P < 0.0167). The incidence of CzIE in MSSA was 12.4%. While blaZ type C was the most common, blaZ type A exhibited the most significant correlation with CzIE. Clinicians must remain alert for blaZ type A strains, as their significant inoculum effect may elevate the probability of cefazolin treatment failure in severe MSSA infections.