The Cefazolin Inoculum Effect and the Presence of type A blaZ Gene according to agr Genotype in Methicillin-Susceptible Staphylococcus aureus Bacteremia

BACKGROUND: Recent data suggests the inoculum effect of methicillin-susceptible Staphylococcus aureus (MSSA) against beta-lactam antibiotics and their association with functionality or genotypic variation of agr locus. METHODS: MSSA blood isolates were collected at a tertiary care hospital in Korea from June 2014 to December 2017. The functionality of the agr operon was measured by δ-hemolysin assays. Multiplex PCR was performed to determine the agr genotype. The cefazolin minimum inhibitory concentrations (MICs) at a high inoculum concentration (~5 × 10(7) CFU/ml) were compared to the MICs at a standard inoculum concentration (~5 × 10(5) CFU/ml) to identify strains with the cefazolin inoculum effect (CIE). The DNA sequencing of blaZ gene was performed to classify the blaZ genotype. RESULTS: Among the 195 MSSA blood isolates, agr genotype I was most common (68.2%), followed by type III (16.4%), type IV (9.2%), and type II (6.2%). Sixty-seven (34.3%) MSSA isolates had dysfunctional agr, but neither CIE nor blaZ genotype was associated with dysfunctional agr. The MSSA with agr type III genotype exhibited significantly higher CIE positivity (agr III 43.8% vs. non-agr III 5.5%, P <0.01) and erythromycin/clindamycin resistance. In the subgroup analysis of type A blaZ possessing MSSA, almost all of the agr III MSSA isolates exhibited CIE, while only 20% of non-agr III isolates had CIE (P <0.01). CONCLUSION: In MSSA blood isolates, CIE might be associated with agr genotype rather than with dysfunctional agr.