血流感染回顾性临床研究及患者免疫功能与预后的基础研究
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摘要
[目的]
评价北京协和医院近三年血流感染的现状,包括患者的基础状态、临床表现及转归、病原学特点及预后相关因素,探查患者基础状态与血流感染预后的相关性。
[方法]
回顾性分析我院2008-2010年住院成人血流感染患者的临床资料和病原学资料。使用设计好的规范化表格收集数据,SPSS软件包对数据进行分析。
[结果]
三年间共收集成人血流感染患者927例,其中97.4%存在慢性基础疾病或需要长期住院治疗的疾病。191例患者为住院期间复数菌感染(20.6%)。引起成人血流感染的病原体中,革兰阳性菌和革兰阴性菌比例相当。共分离菌株1186株,77.2%为院内获得性感染；凝固酶阴性葡萄球菌263株(23.5%),其次是大肠埃希菌204株(18.2%),肠球菌属122(10.9%),不动杆菌属107株(9.5%),金黄色葡萄球菌98株(8.7%)；真菌71(6.0%)株,念珠菌属60株(84.5%)最多见。原发血流感染最为多见,其次是腹腔感染、下呼吸道感染继发血流感染及导管相关血流感染。254例患者住院期间死亡,粗病死率为27.4%；210例(22.7%)患者出现重度败血症或败血症休克,另有159例患者仅表现为一过性败血症,且其中约一半患者未曾接受合理抗生素治疗。血流感染合并重度败血症或败血症休克的患者病死率明显升高(OR=20.41,95%CI：13.93-29.92,x2=318.60,P<0.001)。多因素回归分析中,慢性肺病、中枢神经系统疾病、保留中心静脉置管、有创机械通气、患者年龄≥65岁、接受ICU治疗、复数菌感染均为血流感染不良预后的独立危险因素；而30天内手术史与血流感染不良预后独立负相关。
[结论]
绝大多数血流感染患者存在慢性基础疾病或需要长期住院治疗的疾病,血流感染患者的临床表现和预后不同,部分患者可表现出一过性败血症,即使不给予合理的抗感染治疗,亦能很快治愈；部分患者则表现出重度败血症甚至败血症休克,最终因败血症休克死亡。血流感染的临床表现和预后与患者的基础疾病状态相关。
[目的]
比较血流感染致败血症、重症败血症及败血症休克和非感染性SIRS患者外周血淋巴细胞亚群、炎症因子及趋化因子水平差异,以探讨患者免疫功能与血流感染败血症患者临床表现及转归的关系及败血症与非感染性SIRS患者免疫反应的差异。
[方法]
通过横断面研究,纳入血流感染所致败血症、重度败血症及败血症休克患者,以非感染性SIRS患者及健康志愿者作为对照组,使用流式细胞术对免疫细胞的比例和计数进行测定,使用流式液相多重蛋白定量技术(CBA)测定细胞因子水平,同时使用设计好的表格收集纳入患者的临床资料。所有数据使用SPSS软件包分析。
[结果]
我们收集败血症患者12例,重度败血症及败血症休克患者12例,均为血培养阳性明确血流感染患者,同时纳入11例恶性肿瘤和血管炎导致的非感染性SIRS患者作为对照。三组患者在年龄、基础疾病、所感染病原体、临床表现及外周血白细胞计数均未见显著差异；重症败血症及败血症休克患者淋巴细胞比例降低。三组患者在CD3+T细胞、CD4+T细胞、CD8+T细胞及B细胞的比例及绝对计数上均无显著差异。而无论是NK细胞占淋巴细胞百分比[10.15(7.70,15.35),4.35(2.05,8.05)vs.8.60(4.10,18.10),P=0.041]还是NK细胞绝对计数[114(56,165),50(14,73),103(59,167)cells/mm3；F=4.567,P=0.018],重度败血症及败血症休克组患者均明显降低,重度败血症及败血症休克患者的淋巴细胞降低以NK细胞降低为主。重度败血症及败血症休克较败血症组患者NKT细胞占CD3+T比例明显升高[7.55(4.60,27.70)vs2.45(1.32,4.56),P=0.013]。
无论是血流感染引起的SIRS还是非感染性疾病引起的SIRS反应,血浆IL-6、IL-8、INF-γ、MCP-1、IP-10、MIG、IL-10水平与健康对照组比较,基本都是升高的,而RANTES水平均较健康对照组降低。非感染性SIRS组患者的血浆MIG[3306.20(285.80,8732.34)vs.383.70(165.29,651.86)pg/ml,P=0.018]、IP-10[2269.67(1568.71,2921.59)vs.883.32(621.91,1536.92)pg/ml,P=0.010]和INF-Y[64.00(39.20,83.35)vs.33.99(8.29,70.06)pg/m1,P=0.001]水平均较血流感染所引起的败血症患者升高更为明显。对于败血症患者,血浆MIG、IL-6水平与疾病的预后相关,重度败血症及败血症休克组死亡患者较存活患者的MIG[1816.18(1027,63,2562.66)vs.94.51(23.30,2803.72)pg/ml,P=0.018]、IL-6[365.57(136.99,424.22)vs.40.52(31.56,131.60)pg/ml,P=0.028]水平明显增高。血浆IL-8[63.41(35.21,95.85)vs.169.02(103.01,302.46),p=0.025]和MCP-1[143.00(71.77,410.30)vs.356.22(260.42,549.26),P=0.016]水平与败血症严重程度相关,即重症败血症患者较败血症患者明显升高。
[结论]
重度败血症患者淋巴细胞降低以NK细胞降低更为突出,而重度败血症患者NKT样细胞占CD3+T细胞的比例较败血症组明显升高；血浆工L-8和MCP-1水平与败血症的严重程度相关；MIG和IL-6与重症败血症患者的不良预后相关。MIG、IP-10、INF-γ,在非感染性SIRS时升高较败血症更为明显,提示有进一步研究其作为区分败血症及非感染性SIRS指标的必要性。
[Objective]
In order to evaluate the clinical and microbial characteristics of bloodstream infection, including the underlying state of the patients, clinical manifestations, microbial spectrum, and prognosis as well as the affecting factors, at Peking Union Medical College Hospital in these years, we conducted the retrospective part of the study, trying to explore the association of the state of patients with the clinical manifestation and prognosis.
[Methods]
Retrospectively, we collected the data of the patients with definite BSI, including clinical data microbial data, using standard chart that designed previously. SPSS software was used in the data analysis.
[Results]
Totally we included927cases of bloodstream infection,92.7%of whom were with chronic underlying diseases or the diseases needing long-term hospitalization. One hundred and ninety-one (20.6%) patients with polymicrobial bloodstream infection, we isolated1186strains of microbe from the positive blood cultures in927patients,77.2%being hospital acquired. The five most common isolates were coagulase-negative staphylococcus (23.5%), E.coli (18.2%), Enterococcus spp.(10.9%), Acinetobacter spp.(9.5%) and Staphylococcus Aureues (8.7%), while the G+cocci and the G-rods were comparable. Candida spp. accounting for84.5%, seventy-one isolate of fungi were isolated. According to the sources of bloodstream infection, primary bloodstream infection was the most common, followed by bloodstream infection secondary to abdominal infection, bloodstream infection secondary to lower respiratory tract infection and central-line associated bloodstream infection. There were254patients died during hospitalization with a crude mortality rate of27.4%. Among the927cases,210complicated with severe sepsis and septic shock, however, another159cases, about half of who didn't receive appropriate antibiotic treatment, only underwent a transient sepsis. The patients who complicated severe sepsis and septic shock were with a higher mortality rate (OR=20.41;95%CI,13.93-29.915; χ2=318.60, P=0.000). In the multivariate analysis, chronic lung diseases, diseases of central nervous system, reservation of central-line, invasive mechanical ventilation, age≥65years old, ICU treatment and polymicrobial bloodstream infection were the independent risk factors of poor prognosis, but the operation history within30days was inverse correlated to poor prognosis.
[Conclusions]
Almost all the patients underwent bloodstream infection had at least one type of chronic underlying disease or the disease need long hospitalization, which may lay the patients in different immune states. Some patients experienced only a transient sepsis, while some manifested as severe sepsis and septic shock, due to the different immune states of the patients.
[Objective]
In order to find the immune differences between septic patients and severe septic patients, as well as septic patients and non-infective SIRS patients, we evaluate the subgroups of lymphocytes, proinflammatory cytokines and suppressive inflammatory factors between these patients.
[Methods]
In the prospective part of the study, we included the septic and severe septic and septic shock patients due to bloodstream infection, noninfective SIRS patients due to malignant disease or system arteritis. Evaluate the subgroup of lymphocytes and cytokines and chemokines by flow cytometry and CBA,
[Results]
In the cross-sectional study, prospectively, we included12cases with sepsis,12cases with severe sepsis and septic shock due to definite bloodstream infection. Simultaneously, we included11patients with non-infective SIRS due to lymphoma and arteritis as the control group. By comparison, there was no difference in the absolute counts in peripheral white blood cells, but the patients in severe septic group were with a lower lymphocyte percentage. There were no difference in the percentage and absolute counts of CD3+T cell, CD4+T cell, CD8+T cell, as well as B lymphocytes, but all the subgroups of lymphocytes mentioned above were lower than healthy patients. Both the percentage [10.15(7.70,15.35),4.35(2.05,8.05) vs.8.60(4.10,18.10), P=0.041] and absolute counts [114(56,165),50(14,73),103(59,167) cells/mm3; P=0.018] of NK cell were lower in the severe sepsis and septic shock patients. As the percentage of NKT/CD3+T, the patients with severe sepsis and septic shock were higher than the patients with sepsis [7.55(4.60,27.70) vs2.45(1.32,4.56), P=0.013].
The level of plasma IL-6, IL-8, INF-γ, MCP-1, IP-10, MIG, IL-10were higher in septic group, severe sepsis and septic shock group as well as the non-infective SIRS group than healthy controls. But the level of plasma RANTES were lower in the SIRS patients than healthy controls. The level of plasma MIG [3306.20(285.80,8732.34) vs.383.70(165.29,651.86) pg/ml, P=0.018], IP-10[2269.67(1568.71,2921.59) vs.883.32(621.91,1536.92) pg/ml, P=0.010] and INF-y[64.00(39.20,83.35) vs.33.99(8.29,70.06) pg/ml, P=0.001] were higher in the patients non-infective SIRS than the patients with sepsis, which may be potentially as the biomarkers to discriminate sepsis and non-infective SIRS when the clinical manifestations were similar to each other. IL-8[63.41(35.21,95.85) vs.169.02(103.01,302.46), P=0.025] and MCP-1[143.00(71.77,410.30) vs.356.22(260.42,549.26), P=0.016] were higher in the severe sepsis group than sepsis group. The level of plasma IL-6[365.57(136.99,424.22) vs.40.52(31.56,131.60) pg/ml, P=0.028] and MIG [1816.18(1027.63,2562.66) vs.94.51(23.30,2803.72) pg/ml, P=0.018] were related to prognosis in the patients with severe sepsis and septic shock, which were higher in the patients who were died due to bloodstream infection than the survivors. High level of IL-6and MIG in the early stage of severe sepsis and septic shock indicated a bad prognosis.
[Conclusion]
The patients with severe sepsis were with lower lymphocytes than the patients with sepsis, and the reduction of NK cell was the most prominent. However, the percentage of NKT like cell/CD3+T cell in patients with severe sepsis was higher than that in patients with sepsis. IL-8and MCP-1were higher in patients with severe sepsis than the patients with sepsis. The plasma level of MIG and IL-6were higher in the patients who died due to severe sepsis than survivors. Having the potential to be the discriminated biomarkers, the plasma level of MIG, IP-10and INF-γ in the patients with non-infective SIRS were higher than the patients with sepsis.
评价北京协和医院近三年血流感染的现状,包括患者的基础状态、临床表现及转归、病原学特点及预后相关因素,探查患者基础状态与血流感染预后的相关性。
[方法]
回顾性分析我院2008-2010年住院成人血流感染患者的临床资料和病原学资料。使用设计好的规范化表格收集数据,SPSS软件包对数据进行分析。
[结果]
三年间共收集成人血流感染患者927例,其中97.4%存在慢性基础疾病或需要长期住院治疗的疾病。191例患者为住院期间复数菌感染(20.6%)。引起成人血流感染的病原体中,革兰阳性菌和革兰阴性菌比例相当。共分离菌株1186株,77.2%为院内获得性感染；凝固酶阴性葡萄球菌263株(23.5%),其次是大肠埃希菌204株(18.2%),肠球菌属122(10.9%),不动杆菌属107株(9.5%),金黄色葡萄球菌98株(8.7%)；真菌71(6.0%)株,念珠菌属60株(84.5%)最多见。原发血流感染最为多见,其次是腹腔感染、下呼吸道感染继发血流感染及导管相关血流感染。254例患者住院期间死亡,粗病死率为27.4%；210例(22.7%)患者出现重度败血症或败血症休克,另有159例患者仅表现为一过性败血症,且其中约一半患者未曾接受合理抗生素治疗。血流感染合并重度败血症或败血症休克的患者病死率明显升高(OR=20.41,95%CI：13.93-29.92,x2=318.60,P<0.001)。多因素回归分析中,慢性肺病、中枢神经系统疾病、保留中心静脉置管、有创机械通气、患者年龄≥65岁、接受ICU治疗、复数菌感染均为血流感染不良预后的独立危险因素；而30天内手术史与血流感染不良预后独立负相关。
[结论]
绝大多数血流感染患者存在慢性基础疾病或需要长期住院治疗的疾病,血流感染患者的临床表现和预后不同,部分患者可表现出一过性败血症,即使不给予合理的抗感染治疗,亦能很快治愈；部分患者则表现出重度败血症甚至败血症休克,最终因败血症休克死亡。血流感染的临床表现和预后与患者的基础疾病状态相关。
[目的]
比较血流感染致败血症、重症败血症及败血症休克和非感染性SIRS患者外周血淋巴细胞亚群、炎症因子及趋化因子水平差异,以探讨患者免疫功能与血流感染败血症患者临床表现及转归的关系及败血症与非感染性SIRS患者免疫反应的差异。
[方法]
通过横断面研究,纳入血流感染所致败血症、重度败血症及败血症休克患者,以非感染性SIRS患者及健康志愿者作为对照组,使用流式细胞术对免疫细胞的比例和计数进行测定,使用流式液相多重蛋白定量技术(CBA)测定细胞因子水平,同时使用设计好的表格收集纳入患者的临床资料。所有数据使用SPSS软件包分析。
[结果]
我们收集败血症患者12例,重度败血症及败血症休克患者12例,均为血培养阳性明确血流感染患者,同时纳入11例恶性肿瘤和血管炎导致的非感染性SIRS患者作为对照。三组患者在年龄、基础疾病、所感染病原体、临床表现及外周血白细胞计数均未见显著差异；重症败血症及败血症休克患者淋巴细胞比例降低。三组患者在CD3+T细胞、CD4+T细胞、CD8+T细胞及B细胞的比例及绝对计数上均无显著差异。而无论是NK细胞占淋巴细胞百分比[10.15(7.70,15.35),4.35(2.05,8.05)vs.8.60(4.10,18.10),P=0.041]还是NK细胞绝对计数[114(56,165),50(14,73),103(59,167)cells/mm3；F=4.567,P=0.018],重度败血症及败血症休克组患者均明显降低,重度败血症及败血症休克患者的淋巴细胞降低以NK细胞降低为主。重度败血症及败血症休克较败血症组患者NKT细胞占CD3+T比例明显升高[7.55(4.60,27.70)vs2.45(1.32,4.56),P=0.013]。
无论是血流感染引起的SIRS还是非感染性疾病引起的SIRS反应,血浆IL-6、IL-8、INF-γ、MCP-1、IP-10、MIG、IL-10水平与健康对照组比较,基本都是升高的,而RANTES水平均较健康对照组降低。非感染性SIRS组患者的血浆MIG[3306.20(285.80,8732.34)vs.383.70(165.29,651.86)pg/ml,P=0.018]、IP-10[2269.67(1568.71,2921.59)vs.883.32(621.91,1536.92)pg/ml,P=0.010]和INF-Y[64.00(39.20,83.35)vs.33.99(8.29,70.06)pg/m1,P=0.001]水平均较血流感染所引起的败血症患者升高更为明显。对于败血症患者,血浆MIG、IL-6水平与疾病的预后相关,重度败血症及败血症休克组死亡患者较存活患者的MIG[1816.18(1027,63,2562.66)vs.94.51(23.30,2803.72)pg/ml,P=0.018]、IL-6[365.57(136.99,424.22)vs.40.52(31.56,131.60)pg/ml,P=0.028]水平明显增高。血浆IL-8[63.41(35.21,95.85)vs.169.02(103.01,302.46),p=0.025]和MCP-1[143.00(71.77,410.30)vs.356.22(260.42,549.26),P=0.016]水平与败血症严重程度相关,即重症败血症患者较败血症患者明显升高。
[结论]
重度败血症患者淋巴细胞降低以NK细胞降低更为突出,而重度败血症患者NKT样细胞占CD3+T细胞的比例较败血症组明显升高；血浆工L-8和MCP-1水平与败血症的严重程度相关；MIG和IL-6与重症败血症患者的不良预后相关。MIG、IP-10、INF-γ,在非感染性SIRS时升高较败血症更为明显,提示有进一步研究其作为区分败血症及非感染性SIRS指标的必要性。
[Objective]
In order to evaluate the clinical and microbial characteristics of bloodstream infection, including the underlying state of the patients, clinical manifestations, microbial spectrum, and prognosis as well as the affecting factors, at Peking Union Medical College Hospital in these years, we conducted the retrospective part of the study, trying to explore the association of the state of patients with the clinical manifestation and prognosis.
[Methods]
Retrospectively, we collected the data of the patients with definite BSI, including clinical data microbial data, using standard chart that designed previously. SPSS software was used in the data analysis.
[Results]
Totally we included927cases of bloodstream infection,92.7%of whom were with chronic underlying diseases or the diseases needing long-term hospitalization. One hundred and ninety-one (20.6%) patients with polymicrobial bloodstream infection, we isolated1186strains of microbe from the positive blood cultures in927patients,77.2%being hospital acquired. The five most common isolates were coagulase-negative staphylococcus (23.5%), E.coli (18.2%), Enterococcus spp.(10.9%), Acinetobacter spp.(9.5%) and Staphylococcus Aureues (8.7%), while the G+cocci and the G-rods were comparable. Candida spp. accounting for84.5%, seventy-one isolate of fungi were isolated. According to the sources of bloodstream infection, primary bloodstream infection was the most common, followed by bloodstream infection secondary to abdominal infection, bloodstream infection secondary to lower respiratory tract infection and central-line associated bloodstream infection. There were254patients died during hospitalization with a crude mortality rate of27.4%. Among the927cases,210complicated with severe sepsis and septic shock, however, another159cases, about half of who didn't receive appropriate antibiotic treatment, only underwent a transient sepsis. The patients who complicated severe sepsis and septic shock were with a higher mortality rate (OR=20.41;95%CI,13.93-29.915; χ2=318.60, P=0.000). In the multivariate analysis, chronic lung diseases, diseases of central nervous system, reservation of central-line, invasive mechanical ventilation, age≥65years old, ICU treatment and polymicrobial bloodstream infection were the independent risk factors of poor prognosis, but the operation history within30days was inverse correlated to poor prognosis.
[Conclusions]
Almost all the patients underwent bloodstream infection had at least one type of chronic underlying disease or the disease need long hospitalization, which may lay the patients in different immune states. Some patients experienced only a transient sepsis, while some manifested as severe sepsis and septic shock, due to the different immune states of the patients.
[Objective]
In order to find the immune differences between septic patients and severe septic patients, as well as septic patients and non-infective SIRS patients, we evaluate the subgroups of lymphocytes, proinflammatory cytokines and suppressive inflammatory factors between these patients.
[Methods]
In the prospective part of the study, we included the septic and severe septic and septic shock patients due to bloodstream infection, noninfective SIRS patients due to malignant disease or system arteritis. Evaluate the subgroup of lymphocytes and cytokines and chemokines by flow cytometry and CBA,
[Results]
In the cross-sectional study, prospectively, we included12cases with sepsis,12cases with severe sepsis and septic shock due to definite bloodstream infection. Simultaneously, we included11patients with non-infective SIRS due to lymphoma and arteritis as the control group. By comparison, there was no difference in the absolute counts in peripheral white blood cells, but the patients in severe septic group were with a lower lymphocyte percentage. There were no difference in the percentage and absolute counts of CD3+T cell, CD4+T cell, CD8+T cell, as well as B lymphocytes, but all the subgroups of lymphocytes mentioned above were lower than healthy patients. Both the percentage [10.15(7.70,15.35),4.35(2.05,8.05) vs.8.60(4.10,18.10), P=0.041] and absolute counts [114(56,165),50(14,73),103(59,167) cells/mm3; P=0.018] of NK cell were lower in the severe sepsis and septic shock patients. As the percentage of NKT/CD3+T, the patients with severe sepsis and septic shock were higher than the patients with sepsis [7.55(4.60,27.70) vs2.45(1.32,4.56), P=0.013].
The level of plasma IL-6, IL-8, INF-γ, MCP-1, IP-10, MIG, IL-10were higher in septic group, severe sepsis and septic shock group as well as the non-infective SIRS group than healthy controls. But the level of plasma RANTES were lower in the SIRS patients than healthy controls. The level of plasma MIG [3306.20(285.80,8732.34) vs.383.70(165.29,651.86) pg/ml, P=0.018], IP-10[2269.67(1568.71,2921.59) vs.883.32(621.91,1536.92) pg/ml, P=0.010] and INF-y[64.00(39.20,83.35) vs.33.99(8.29,70.06) pg/ml, P=0.001] were higher in the patients non-infective SIRS than the patients with sepsis, which may be potentially as the biomarkers to discriminate sepsis and non-infective SIRS when the clinical manifestations were similar to each other. IL-8[63.41(35.21,95.85) vs.169.02(103.01,302.46), P=0.025] and MCP-1[143.00(71.77,410.30) vs.356.22(260.42,549.26), P=0.016] were higher in the severe sepsis group than sepsis group. The level of plasma IL-6[365.57(136.99,424.22) vs.40.52(31.56,131.60) pg/ml, P=0.028] and MIG [1816.18(1027.63,2562.66) vs.94.51(23.30,2803.72) pg/ml, P=0.018] were related to prognosis in the patients with severe sepsis and septic shock, which were higher in the patients who were died due to bloodstream infection than the survivors. High level of IL-6and MIG in the early stage of severe sepsis and septic shock indicated a bad prognosis.
[Conclusion]
The patients with severe sepsis were with lower lymphocytes than the patients with sepsis, and the reduction of NK cell was the most prominent. However, the percentage of NKT like cell/CD3+T cell in patients with severe sepsis was higher than that in patients with sepsis. IL-8and MCP-1were higher in patients with severe sepsis than the patients with sepsis. The plasma level of MIG and IL-6were higher in the patients who died due to severe sepsis than survivors. Having the potential to be the discriminated biomarkers, the plasma level of MIG, IP-10and INF-γ in the patients with non-infective SIRS were higher than the patients with sepsis.
引文
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