Kang JS, et al. J Korean Med Sci. 2019 Apr;34(18):e140. https://doi.org/10.3346/jkms.2019.34.e140

The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05–1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20–1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03–1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27–0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17–5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia.

Kang JS, et al. J Korean Med Sci. 2021 Sep;36(43):e273. https://doi.org/10.3346/jkms.2021.36.e273

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. 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. 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). In MSSA blood isolates, CIE might be associated with agr genotype rather than with dysfunctional agr.

Lee S, et al. J Korean Med Sci. 2017 Sep;32(9):1445-1450. https://doi.org/10.3346/jkms.2017.32.9.1445

Lee JE, et al. Infect Chemother. 2016 Dec;48(4):334-337. https://doi.org/10.3947/ic.2016.48.4.334