a Department of Infectious Diseases , Örebro University Hospital , Örebro , Sweden.
b School of Health and Medical Sciences , Örebro University , Örebro , Sweden.
Infect Dis (Lond). 2019 Mar;51(3):216-226. doi: 10.1080/23744235.2018.1562205. Epub 2019 Jan 24.
Staphylococcus aureus bacteraemia is a disease with varying presentation, ranging from uncomplicated to life-threatening infections. In S. aureus bacteraemia, a high load of bacterial DNA in blood has been linked to mortality. We hypothesized that a high DNA load would also be linked to the presence of sepsis, and to high C-reactive protein (CRP) and lymphopaenia, indicating inflammation and immunosuppression.
Twenty-seven patients with culture-proven S. aureus bacteraemia, 13 (48%) with sepsis and six (22%) non-survivors, were enrolled in a prospective study. Blood samples were collected on days 0, 1-2, 3-4, 6-8, 13-15 and 26-30, and subjected to droplet digital PCR targeting the nuc gene to determine the nuc DNA load.
nuc DNA was detected on days 0-2 in 22 patients (81%), and on days 6-8 in three patients (all non-survivors). The nuc DNA load on days 1-2 was significantly elevated in patients with sepsis (median 2.69 versus 1.32 log10 copies/mL; p = .014) and in non-survivors (median 2.5 versus 1.0 log10 copies/mL; p = .033). Patients with a high nuc DNA load (>3.0 log10 copies/mL) on days 1-2 had significantly elevated CRP levels at all timepoints, and significantly decreased lymphocyte counts on days 0, 1-2, 13-15 and 26-30.
Our results indicate that a high initial load of S. aureus DNA in blood is associated with sepsis, mortality and persistent immune dysregulation in S. aureus bacteraemia patients. Further studies are needed to define the role of bacterial DNA load monitoring in the management of S. aureus bacteraemia.
金黄色葡萄球菌菌血症表现多样，从单纯感染到危及生命的感染不等。在金黄色葡萄球菌菌血症中，血液中细菌 DNA 负荷高与死亡率相关。我们假设高 DNA 负荷也与脓毒症的发生以及高 C 反应蛋白（CRP）和淋巴细胞减少有关，这表明存在炎症和免疫抑制。
我们对 27 例培养阳性的金黄色葡萄球菌菌血症患者进行了前瞻性研究，其中 13 例（48%）合并脓毒症，6 例（22%）死亡。在第 0、1-2、3-4、6-8、13-15 和 26-30 天采集血样，采用针对 nuc 基因的液滴数字 PCR 检测 nuc DNA 负荷。
22 例患者（81%）在第 0-2 天检测到 nuc DNA，3 例患者（均为死亡患者）在第 6-8 天检测到 nuc DNA。脓毒症患者（中位数 2.69 与 1.32 log10 拷贝/mL；p=0.014）和死亡患者（中位数 2.5 与 1.0 log10 拷贝/mL；p=0.033）第 1-2 天 nuc DNA 负荷显著升高。第 1-2 天 nuc DNA 负荷高（>3.0 log10 拷贝/mL）的患者所有时间点 CRP 水平均显著升高，第 0、1-2、13-15 和 26-30 天淋巴细胞计数显著降低。
我们的结果表明，血液中金黄色葡萄球菌 DNA 的初始负荷高与金黄色葡萄球菌菌血症患者的脓毒症、死亡率和持续免疫失调相关。需要进一步研究来确定细菌 DNA 负荷监测在金黄色葡萄球菌菌血症管理中的作用。
