Infect Chemother.  2019 Dec;51(4):376-385. 10.3947/ic.2019.51.4.376.

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

• Lee SO
• Lee S
• Park S
• Lee JE
• Lee SH

• KMID: 2466470
• DOI: http://doi.org/10.3947/ic.2019.51.4.376

Abstract

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 × 10⁷ CFU/ml) were compared to the MICs at a standard inoculum concentration (~5 × 10⁵ 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.

Keyword

Staphylococcus aureus; Quorum sensing; Cefazolin; Inoculum effect

MeSH Terms

Anti-Bacterial Agents
Bacteremia*
Cefazolin*
Genotype*
Korea
Microbial Sensitivity Tests
Multiplex Polymerase Chain Reaction
Operon
Quorum Sensing
Sequence Analysis, DNA
Staphylococcus aureus*
Staphylococcus*
Tertiary Healthcare
Anti-Bacterial Agents
Cefazolin

Figure

• 

  Figure 1 (A) Proportion of cefazolin inoculum effect (CIE) positivity, (B) blaZ genotype, (C) erythromycin resistance between agr type III and non agr type III methicillin susceptible Staphylococcus aureus.

• 

  Figure 2 (A) Proportion of cefazolin inoculum effect positivity according to the agr genotype, (B) erythromycin resistance, (C) agr functionality in subgroup analysis among Methicillin susceptible Staphylococcus aureus with type A blaZ gene.

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