植入型心脏电子装置无症状囊袋感染的危险因素、预后与炎症因子预测价值的分析

Analysis of Risk Factors and the Predictive Value of Inflammatory Factors of Cardiac Implantable Electronic Device Relevant Asymptomatic Pockets Infections

摘要: 目的：将心脏植入电子装置(cardiac implantable electronic device, CIED)囊袋微生物培养阳性但却不合并任何临床感染症状(囊袋周围皮肤出现红肿热痛、破溃、化脓等症状可以确诊囊袋感染或CIED相关的感染性心内膜炎)的情况定义为无症状囊袋感染，即亚临床囊袋感染。本研究旨在探索无症状囊袋感染的危险因素、预后以及炎症因子水平与无症状CIED囊袋感染之间的关系，寻求早期识别亚临床囊袋感染的方法。方法：连续入选2011年1月至2014年10月在卫生部北京医院及阜外医院行CIED的患者一共179例(排除临床确诊囊袋感染或植入性心脏电子装置相关感染性心内膜炎患者)，留取血培养和囊袋组织培养，收集相关临床资料，相关结果进行单因素及多因素回归分析。并对病人进行为期60个月的随访。在上述病人中随机抽取108例行5种炎性因子(CRP、IL-1、IL-6、MCP、PCT)测定，分析其中囊袋培养阴性组与囊袋培养阳性组的炎症因子的差异。抽取40例正常人的炎症因子与上述患者进行比较。结果：179例行心脏植入电子装置更换的患者，血培养均为阴性，所有入选患者中，囊袋组织培养结果阳性25例(14.0%)。检出率最高的致病菌为凝固酶阴性葡萄球菌，共19例(76.0%)。多因素Logistic回归分析发现男性(P = 0.001, OR = 14.001, 95%CI: 2.825~69.401)，术前三月内抗生素使用大于10天(P = 0.002, OR = 27.935, 95%CI: 3.446~226.437)，服用抗血小板药物(P = 0.008, OR = 3.761, 95%CI: 1.406~10.058)为无症状亚临床囊袋感染的独立危险因素。囊袋培养阳性组随访期内有4%的患者(1人/25人)因囊袋感染返院清创，阴性组无人报告临床囊袋感染。CIED更换患者的炎性因子的数值(CRP、IL-1、IL-6、MCP、PCT)明显高于正常人对照组(P = 0.001)，囊袋培养阳性的患者与囊袋培养阴性的患者的炎性因子之间不存在显著差异。剔除基础疾病后的亚组分析中，CIED更换患者的炎症因子仍明显高于正常对照组，囊袋培养阳性与囊袋培养阴性的患者之间炎性因子仍未见显著差异。结论：临床上无感染表现的CIED植入患者中，无症状囊袋感染发生率约14.0%，其独立的危险因素是男性，长期服用抗血小板药物与术前3月内使用抗生素大于10天。无症状囊袋感染的患者迟发临床囊袋感染的几率为4%。CIED更换者的炎性因子整体水平明显升高，提示患者可能处于炎症反应激活的状态，但利用炎性因子检测协助诊断CIED亚临床感染目前证据尚不充分。

Abstract: Objective: To investigate the risk factors, prognosis and the predictive value of 5 different inflammatory factors in CIED associated subclinical generator pocket infections (asymptomatic infection also called subclinical. Methods: A total of 179 patients undergoing replacement of CIED (cardiac implanted electronic devices) in Beijing hospital and Fuwai Hospital between January 2011 and October 2014 were recruited. Microbiological cultures of blood and generator pockets were consecutively obtained. Patients with clinical evidence of CIED infection were excluded. Patients were regularly followed up 60 months after discharge. Univariate and multivariable analyses were performed to identify significant risk factors for positive generator pockets culture patients. Five different inflammatory factors (CRP, IL-1, IL-6, MCP, PCT) were measured in 108 patients randomly selected from patients above, and the differences of inflammatory factors were analyzed between patients with positive pocket tissue cultures and patients with negative pocket tissue cultures. The inflammatory factors of 40 normal people were compared with the patients above too. Results: All blood cultures of the 179 patients were negative. Positive cultures from the generator pocket were found in 25 patients (14.0%). The most common bacteria isolated were coagulase negative staphylococci (76.0%). A multivariable logistic regression identified that male sex (P = 0.001, OR = 14.001, 95%CI: 2.825~69.401), antibiotic use 3 months before implantation (P = 0.002, OR = 27.935, 95%CI: 3.446~226.437), antiplatelet therapy (P = 0.008, OR = 3.761, 95%CI: 1.406~10.058) as independent risk factors for asymptomatic bacterial colonization of generator pockets. 4% patients with positive pocket culture showed clinical sign of infection during 60 months follow-up, while none of patients with negative pocket culture reported any sign of CIED relevant infections. Significant difference in inflammatory factors (including CRP, IL-1, IL-6, MCP, PCT) had been identified between patients who replaced CIED and the normal control group, however there was no relevance between inflammatory factors and generator pocket cultures even when all the fundamental clinical complications were excluded. Conclusion: 14.0% of patients undergoing CIED replacement have an asymptomatic bacterial colonization of generator pockets. Independent factors for positive pockets culture is male sex, antibiotic use 3 months before implantation, antiplatelet therapy 0.4% of patients with positive pocket culture develop clinical CIED infection. Inflammatory factors are significantly elevated in patients undergoing CIED replacement suggesting a strong inflammatory reaction in those patients, however, there is not sufficient evidence indicating predictive value of inflammatory factors in early diagnosis of subclinical CIED infections.