Division of Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Division of Infectious Diseases, Inflammation Center, Helsinki University Central Hospital, Meilahti Triangle Hospital, Helsinki, Finland.
PLoS One. 2021 May 27;16(5):e0252046. doi: 10.1371/journal.pone.0252046. eCollection 2021.
Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been shown to predict prognosis in sepsis. However, MMP-8 and TIMP-1 in Staphylococcus aureus bacteremia (SAB) lacks evaluation and their role in the pathogenesis of SAB is unclear.
MMP-8 and TIMP-1 and MMP-8/TIMP-1 molar ratio were determined at days 3, 5 and 28 from positive blood cultures in patients with methicillin-sensitive SAB and the connection to disease severity and early mortality was determined.
Altogether 395 SAB patients were included. Patients with severe sepsis or infection focus presented higher MMP-8 levels at day 3 and 5 (p<0.01). Higher day 3 and 5 MMP-8 levels were associated to mortality at day 14 and 28 (p<0.01) and day 90 (p<0.05). Day 3 MMP-8 cut-off value of 203 ng/ml predicted death within 14 days with an area under the curve (AUC) of 0.70 (95% CI 0.57-0.82) (p<0.01). Day 5 MMP-8 cut-off value of 239 ng/ml predicted death within 14 days with an AUC of 0.76 (95% CI 0.65-0.87) (p<0.001). The results for MMP-8/TIMP-1 resembled that of MMP-8. TIMP-1 had no prognostic impact. In Cox regression analysis day 3 or 5 MMP-8 or day 3 MMP-8/TIMP-1 had no prognostic impact whereas day 5 MMP-8/TIMP-1 predicted mortality within 14 days (HR, 4.71; CI, 95% 1.67-13.3; p<0.01).
MMP-8 and MMP-8/TIMP-1 ratio were high 3-5 days after MS-SAB diagnosis in patients with an infection focus, severe sepsis or mortality within 14 days suggesting that matrix metalloproteinase activation might play a role in severe SAB.
基质金属蛋白酶-8（MMP-8）和金属蛋白酶组织抑制剂-1（TIMP-1）已被证明可以预测脓毒症的预后。然而，金黄色葡萄球菌菌血症（SAB）中的 MMP-8 和 TIMP-1 尚未得到评估，其在 SAB 发病机制中的作用尚不清楚。
在培养出阳性血培养物后的第 3、5 和 28 天，测定耐甲氧西林敏感的 SAB 患者的 MMP-8 和 TIMP-1 以及 MMP-8/TIMP-1 摩尔比，并确定与疾病严重程度和早期死亡率的关系。
共纳入 395 例 SAB 患者。患有严重脓毒症或感染灶的患者，在第 3 和 5 天 MMP-8 水平更高（p<0.01）。第 3 和 5 天较高的 MMP-8 水平与第 14、28 天（p<0.01）和第 90 天（p<0.05）的死亡率相关。第 3 天 MMP-8 截断值为 203ng/ml 预测 14 天内死亡的曲线下面积（AUC）为 0.70（95%CI 0.57-0.82）（p<0.01）。第 5 天 MMP-8 截断值为 239ng/ml 预测 14 天内死亡的 AUC 为 0.76（95%CI 0.65-0.87）（p<0.001）。MMP-8/TIMP-1 的结果与 MMP-8 相似。TIMP-1 对预后没有影响。在 Cox 回归分析中，第 3 或 5 天的 MMP-8 或第 3 天的 MMP-8/TIMP-1 对 14 天内的死亡率没有影响，而第 5 天的 MMP-8/TIMP-1 预测了 14 天内的死亡率（HR，4.71；CI，95%1.67-13.3；p<0.01）。
在有感染灶、严重脓毒症或 14 天内死亡的耐甲氧西林敏感金黄色葡萄球菌菌血症患者中，MMP-8 和 MMP-8/TIMP-1 比值在诊断后 3-5 天升高，提示基质金属蛋白酶激活可能在严重 SAB 中发挥作用。
