Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea.
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Sci Rep. 2020 Nov 26;10(1):20697. doi: 10.1038/s41598-020-77729-0.
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.
金黄色葡萄球菌的辅助基因调节（agr）基因座是一种群体感应毒力调节因子。尽管有许多关于 agr 功能障碍对金黄色葡萄球菌感染结果的影响的研究，但迄今为止尚无系统评价。我们系统地检索了报告侵袭性金黄色葡萄球菌感染结果和其致病株中 agr 功能障碍比例的临床研究，并进行了荟萃分析，以获得 agr 功能障碍与功能正常的侵袭性金黄色葡萄球菌感染结果的比值比（odds ratio，OR）的估计值。通过我们的研究策略，共确定了 289 篇文章，其中 20 篇研究进行了荟萃分析，以分析 agr 功能障碍对侵袭性金黄色葡萄球菌感染结果的影响。agr 功能障碍通常与不良结局相关（OR 1.32，95%置信区间 1.05-1.66），并且在侵袭性耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）感染中，agr 功能障碍对结局的影响更为显著（OR 1.54，95%置信区间 1.20-1.97）。有 9 项研究对 agr 功能障碍对侵袭性金黄色葡萄球菌感染 30 天死亡率的影响进行了荟萃分析。具有 agr 功能障碍的侵袭性 MRSA 感染表现出更高的 30 天死亡率（OR 1.40，95%置信区间 1.03-1.90），而具有功能正常的 agr 的感染则较低。另一方面，具有 agr 功能障碍的侵袭性 MSSA 感染表现出较低的 30 天死亡率（OR 0.51，95%置信区间 0.27-0.95）。在 MRSA 感染部位的事后亚组分析中，agr 功能障碍与 MRSA 肺炎中的 30 天死亡率较高相关（OR 2.48，95%置信区间 1.17-5.25）。agr 功能障碍对侵袭性金黄色葡萄球菌感染结果的影响可能因各种情况而异，如苯唑西林敏感性和感染部位。agr 功能障碍通常与不良临床结局相关，其影响在 MRSA 和肺炎中更为显著。agr 功能障碍可能适用于难以根除病灶（如肺炎）的侵袭性 MRSA 感染的预后预测。
