Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, SE 751 85, Uppsala, Sweden.
Section of Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Sci Rep. 2023 Feb 3;13(1):1964. doi: 10.1038/s41598-023-28880-x.
Early secondary sepsis (ESS), occurring after recent inflammatory activation is associated with a reduced inflammatory response. If this attenuation also is associated with decreased bacterial killing, the need for antibiotic efficacy might be greater than in primary sepsis (PS). This prospective, randomised interventional study compares bacterial killing in ESS and PS in a large animal intensive care sepsis model. 38 pigs were intravenously administered live Escherichia coli for 3 h. Before baseline ESS was pre-exposed to endotoxin 24 h, whereas PS was not. Bacterial growth was measured in organs immediately post-mortem, repeatedly during 6 h in blood in vivo and for blood intrinsic bactericidal capacity ex vivo. Splenic growth was lower in ESS animals, than in PS animals (3.31 ± 0.12, vs. 3.84 ± 0.14 log CFU/mL, mean ± SEM) (p < 0.01) with a similar trend in hepatic growth (p = NS). Blood bacterial count at 2 h correlated with splenic bacterial count in ESS (ESS: r = 0.71, p < 0.001) and to blood killing capacity in PS (PS: r = 0.69, p < 0.001). Attenuated inflammation in ESS is associated with enhanced antibacterial capacities in the spleen. In ESS blood bacterial count is related to splenic killing and in PS to blood bactericidal capacity. The results suggest no increased need for synergistic antibiotic combinations in ESS.
早期二次脓毒症 (ESS) 发生于近期炎症激活之后,与炎症反应减弱有关。如果这种衰减也与细菌杀伤减少有关,那么抗生素疗效的需求可能比原发性脓毒症 (PS) 更大。本前瞻性、随机干预研究在大型动物重症监护脓毒症模型中比较了 ESS 和 PS 中的细菌杀伤。38 头猪静脉给予活大肠杆菌 3 小时。在 ESS 之前,ESS 预先暴露于内毒素 24 小时,而 PS 没有。在死后立即测量器官中的细菌生长,在体内血液中重复测量 6 小时,并在体外测量血液固有杀菌能力。ESS 动物的脾生长低于 PS 动物(3.31 ± 0.12,vs. 3.84 ± 0.14 log CFU/mL,平均值 ± SEM)(p < 0.01),肝生长也有类似趋势(p = NS)。ESS 中 2 小时的血细菌计数与脾细菌计数相关(ESS:r = 0.71,p < 0.001),与 PS 中的血杀菌能力相关(PS:r = 0.69,p < 0.001)。ESS 中炎症反应减弱与脾内抗菌能力增强有关。ESS 中的血细菌计数与脾杀伤有关,而 PS 中的血杀菌能力与血杀菌能力有关。结果表明,ESS 中没有增加对协同抗生素组合的需求。