侵袭性真菌感染患者细胞色素P_(450)2C19遗传多态性分析

目的 探讨细胞色素P_(450)2C19(CYP2C19)遗传多态性在侵袭性真菌感染患者中的分布情况.方法 采用PCR-限制性片段长度多态性(PCR-RFLP)技术检测134例侵袭性真菌感染患者和134例健康对照者CYP2C19基因2个主要单核苷酸多态性位点CYP2C19*2和CYP2C19*3的基因型,比较两组各等位基因频率及代谢型的比例.结果 侵袭性真菌感染病例组CYP2C19*1等位基因频率为58.2%,CYP2C19*2等位基因频率为36.6%,CYP2C19*3 等位基因频率为5.2%.对照组CYP2C19*1等位基因频率为63.4%,CYP2C19*2 等位基因频率为34.3%,CYP2C19*3 等位基因频率为2.2%,两组间差异无统计学意义.侵袭性真菌感染组纯合快代谢、杂合快代谢以及慢代谢型比例分别为33.6%、50.0%、16.4%,对照组比例为40.3%、48.5%、11.2%,两组差异无统计学意义.结论 在本组侵袭性真菌感染患者以及健康人群中存在明显CYP2C19遗传多态性,且近2/3患者为杂合快代谢型或慢代谢型.因此,在治疗过程中应重视CYP2C19遗传多态性对药物代谢的影响.     

高分辨熔解方法的建立及在真菌感染患者CYP2C19遗传多态性检测中的应用

目的 探讨高分辨熔解方法 (high resolution melting,HRM)检测真菌感染患者CYP2C19遗传多态性的可行性.方法 建立HRM方法 检测CYP2C19 * 2和CYP2C19 * 3两个多态性位点的基因型,并与传统方法 PCR-限制性片段长度多态性(PCR-RFLP)及序列分析结果 相比较,进一步应用于47例真菌感染患者基因型的检测与分析.结果 2种方法 检测CYP2C19 * 2和CYP2C19* 3基因型结果 完全一致,与DNA序列分析结果 也相吻合,而HRM方法 操作更为简便,耗时更短.47份临床标本检测结果 显示,CYP2C19的2个多态性位点存在不同基因型,CYP2C19 * 1/ * 1所占比例为48.9%(23/47),CYP2C19 * 1/ * 2为25.5%(12/47),CYP2C19 * 1/ * 3为6.4%(3/47),CYP2C19 * 2/ * 2为12.8%(6/47),CYP2C19 * 2/ * 3为6.4%(3/47).结论 HRM方法 能有效检测CYP2C19基因多态性,且较PCR-RFLP方法 更为简便、快速.此外,CYP2C19基因在真菌感染患者中存在明显的遗传多态性.     

医院获得性念珠菌血症109例临床特点及预后因素分析

Objective To understand the clinical epidemiology of nosocomial candidemia in Huashan Hospital during a 10-year period. Methods One hundred and nine cases of nosocomial candidemia in Huashan Hospital affiliated Fudan University during the period of 1998- 2007 were retrospectively reviewed. The underlying conditions, risk factors, clinical manifestations, treatment and outcome were described. The prognostic factors were analyzed by chi square test or Fisher exact probability test. Multivariate analysis was done by multiple Logistic regression. Results The average annual incidence of nosocomial candidemia during the study period was 0.28/10 000 patients per day.The most common pathogen was C. albicans (59/109,54.1%), followed by C. tropicalis (20/109,18.3%), then C. parapsilosis (11/109, 10. 1%), C. glabrata (11/109, 10.1%), and other Candida spp. (8/109, 7.3% ). Underlying diseases frequently identified included diabetes (50,45.9%), solid malignancy (32, 29.4%), head trauma (13, 11. 9%) and stroke (12, 11.0%).There were 37 cases who died or deteriorated. The overall mortality was 34.0% and the attributable mortality was 22. 0% (24/109). In multivariate prognostic analysis, retention of central venous catheters (OR: 5.42, 95% CI: 1.68-17.41, P＝0.005), corticosteroid medication (OR: 3.69,95% CI: 1.10-12.34, P=0. 034), and severe sepsis on the day of candidemia (OR: 2.94, 95% CI:1.72-15. 21, P = 0. 003) were factors independently correlated to increased mortality. Furthermore,adequate antifungal therapy was the only independent predictor of decreased overall mortality (OR: 0. 27,95% CI: 0. 09-0. 78,P=0.015). Conclusions The incidence of nosocomial candidemia in our hospital has been increasing during the past decade. Timely diagnosis and treatment plays a key role in the management of nosocomial candidemia,     

非艾滋病相关隐球菌脑膜炎的预后因素分析

目的 探讨影响非艾滋病(AIDS)相关隐球菌脑膜炎(隐脑)的预后因素.方法 收集复旦大学附属华山医院感染科11年(1997至2007年)间收治的154例非MDS相关隐脑病例,并随访1年,分析影响其病死率的危险因素.结果 随访1年中,全因病死率为28.7%(41/143,11例失访),归因病死率为19.6%(28/143).单因素分析结果 显示,与全因病死率增加显著相关的因素包括年龄≥60岁、血液恶性肿瘤、实体恶性肿瘤、发病至确诊时间>4个月、病程中出现意识障碍(昏迷、癫痫发作、脑疝),以及行脑脊液脑室外引流或分流术等.与全因病死率减少显著相关的因素包括初始治疗方案中含有两性霉素B者、初始治疗方案中含有氟胞嘧啶者,以及两性霉素B鞘内注射者.Cox多元回归分析结果 显示,与全因病死独立相关的因素包括年龄≥60岁、发病至确诊时间>4个月、昏迷、脑疝,以及初始治疗方案不含两性霉素B者;与归因病死独立相关的因素包括发病至确诊时间>4个月、脑疝以及初始治疗方案不含两性霉索B者.结论 非AIDS相关隐脑患者中年龄≥60岁、意识障碍、发病至确诊时间>4个月者预后不佳,应用两性霉素B的初始治疗对预后改善起着关键性作用.     

医院获得性念珠菌血症109例临床特点及预后因素分析

目的 了解医院获得性念珠菌血症的临床特征.方法 回顾性分析复旦大学附属华山医院10年(1998-2007年)间医院获得性念珠菌血症109例,描述其基础特征、相关危险因素、临床表现、治疗和转归等,并采用x2检验或Fisher精确概率法进行预后单因素分析,采用多元Logistic回归进行预后多因素分析.结果 念珠菌血症平均发病率为每天0.28/10 000例患者.血流感染致病菌株中白念珠菌59例,占54.1%;其次为热带念珠菌20例,占18.3%;光滑念珠菌11例,占10.1%;近平滑念珠菌11例,占10.1%;其他念珠菌8例,占7.3%.常见基础疾病包括糖尿病50例,占45.9%;实体恶性肿瘤32例,占29.4%;脑部外伤13例,占11.9%;脑卒中12例,占11.0%.出院时死亡或病情恶化37例,总病死率为34.0%,其中归因病死率22.0%(24/109).预后多元回归分析显示,与患者出院病死率增高独立相关的因素包括未置换深静脉导管(OR:5.42,95%CI:1.68～17.41,P＝0.005)、使用糖皮质激素(OR:3.69,95%CI:1.10～12.34,P＝0.034)以及血培养阳性当天重型脓毒症(OR:2.94,95%CI:1.72～15.21,P＝0.003),而接受合理抗真菌治疗者出院病死率较低(OR:0.27,95%CI:0.09～0.78,P＝0.015).结论 医院获得性念珠菌血症发病率近10年呈上升趋势,而早期诊断和及时治疗是降低其病死率的关键.

Abstract：

Objective To understand the clinical epidemiology of nosocomial candidemia in Huashan Hospital during a 10-year period. Methods One hundred and nine cases of nosocomial candidemia in Huashan Hospital affiliated Fudan University during the period of 1998- 2007 were retrospectively reviewed. The underlying conditions, risk factors, clinical manifestations, treatment and outcome were described. The prognostic factors were analyzed by chi square test or Fisher exact probability test. Multivariate analysis was done by multiple Logistic regression. Results The average annual incidence of nosocomial candidemia during the study period was 0.28/10 000 patients per day.The most common pathogen was C. albicans (59/109,54.1%), followed by C. tropicalis (20/109,18.3%), then C. parapsilosis (11/109, 10. 1%), C. glabrata (11/109, 10.1%), and other Candida spp. (8/109, 7.3% ). Underlying diseases frequently identified included diabetes (50,45.9%), solid malignancy (32, 29.4%), head trauma (13, 11. 9%) and stroke (12, 11.0%).There were 37 cases who died or deteriorated. The overall mortality was 34.0% and the attributable mortality was 22. 0% (24/109). In multivariate prognostic analysis, retention of central venous catheters (OR: 5.42, 95% CI: 1.68-17.41, P＝0.005), corticosteroid medication (OR: 3.69,95% CI: 1.10-12.34, P=0. 034), and severe sepsis on the day of candidemia (OR: 2.94, 95% CI:1.72-15. 21, P = 0. 003) were factors independently correlated to increased mortality. Furthermore,adequate antifungal therapy was the only independent predictor of decreased overall mortality (OR: 0. 27,95% CI: 0. 09-0. 78,P=0.015). Conclusions The incidence of nosocomial candidemia in our hospital has been increasing during the past decade. Timely diagnosis and treatment plays a key role in the management of nosocomial candidemia,     

感染相关性极度血小板增多症一例

患者男,59岁.因持续发热20余天入院.入院前20余天出现发热,体温最高达38.9℃,不伴畏寒、咽痛、咳嗽,无尿路刺激症状,无腹痛、腹泻,无关节、肌肉痛,无皮疹.     

医院获得性念珠菌血症109例临床特点及预后因素分析

Objective To understand the clinical epidemiology of nosocomial candidemia in Huashan Hospital during a 10-year period. Methods One hundred and nine cases of nosocomial candidemia in Huashan Hospital affiliated Fudan University during the period of 1998- 2007 were retrospectively reviewed. The underlying conditions, risk factors, clinical manifestations, treatment and outcome were described. The prognostic factors were analyzed by chi square test or Fisher exact probability test. Multivariate analysis was done by multiple Logistic regression. Results The average annual incidence of nosocomial candidemia during the study period was 0.28/10 000 patients per day.The most common pathogen was C. albicans (59/109,54.1%), followed by C. tropicalis (20/109,18.3%), then C. parapsilosis (11/109, 10. 1%), C. glabrata (11/109, 10.1%), and other Candida spp. (8/109, 7.3% ). Underlying diseases frequently identified included diabetes (50,45.9%), solid malignancy (32, 29.4%), head trauma (13, 11. 9%) and stroke (12, 11.0%).There were 37 cases who died or deteriorated. The overall mortality was 34.0% and the attributable mortality was 22. 0% (24/109). In multivariate prognostic analysis, retention of central venous catheters (OR: 5.42, 95% CI: 1.68-17.41, P＝0.005), corticosteroid medication (OR: 3.69,95% CI: 1.10-12.34, P=0. 034), and severe sepsis on the day of candidemia (OR: 2.94, 95% CI:1.72-15. 21, P = 0. 003) were factors independently correlated to increased mortality. Furthermore,adequate antifungal therapy was the only independent predictor of decreased overall mortality (OR: 0. 27,95% CI: 0. 09-0. 78,P=0.015). Conclusions The incidence of nosocomial candidemia in our hospital has been increasing during the past decade. Timely diagnosis and treatment plays a key role in the management of nosocomial candidemia,