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1、重症患者如何合理应用抗真菌药物,嘉兴市第二医院ICU 蔡继明,Russell E. Lewis, PharmD；Current Concepts in Antifungal Pharmacology；Mayo Clin Proc. August 2011;86(8):805-817,重症患者侵袭性真菌感染流行病学现状 临床常用抗真菌药物特点 关于抗真菌药物的联合应用 重症患者念珠菌血症诊治策略 . 重症患者如何合理应用抗真菌药物？,重症患者侵袭性真菌感染诊断和治疗指南 重症医学分会,抗真菌治疗原则 由于真菌感染的复杂性，目前多提倡分层治疗，包括预防性治疗、经验性治疗、抢先治疗及目标性治疗,问题
2、,经验&预防用药？什么样的病人是真菌感染的高危人群？什么病人需要预防应用抗真菌药物？用什么药预防？预防什么？预防应用需要用多长时间？这样的预防有效吗？,相关概念,ProphylaxisEmpirical antifungal therapy in patients with neutropenia and fever Preemptive antifungal therapy in patients with some signs or markers of diagnostic probability Targeted therapy,Magorzata Mikulska & Claudio
3、 Viscoli，Current Role of Echinocandins in the Management of Invasive Aspergillosis，Curr Infect Dis Rep (2011) 13:517527,IFI危险因素,Meinolf Karthaus etal,germany;Wait and see or rush and switch? New questions for the management of patients with febrile neutropenia receiving antifungal prophylaxis，2011 B
4、lackwell Verlag Gmbh Mycoses 54 (Suppl 1), 16,ICU念珠菌血症危险因素,Invasive candidiasis in intensive care units in China: a multicentre prospective observational study； J Antimicrob Chemother 2013; 68: 16601668,ICU- IFI危险因素,How to select an antifungal agent in critically ill patients；Journal of Critical Car
5、e (2013) 28, 717727,相关研究,多烯类与棘白菌素在粒细胞减少癌症患者或HSCT的 抗真菌预防 氟康唑（75天）减少播散性念珠菌感染及相关死亡率 voriconazole Posaconazole. 待决问题何人何时何药其他,Meinolf Karthaus etal,germany;Wait and see or rush and switch? New questions for the management of patients with febrile neutropenia receiving antifungal prophylaxis，2011 Blackwel
6、l Verlag Gmbh Mycoses 54 (Suppl 1), 16,Preventing invasive fungal disease in patients with haematological malignancies and the recipients of haematopoietic stem cell transplantation: practical aspects; J Antimicrob Chemother 2013; 68 Suppl 3: iii5iii15,How to select an antifungal agent in critically
7、 ill patients；Journal of Critical Care (2013) 28, 717727,Lake Wakatipu and Queenstown.,问题,这个病人经验性治疗合理吗？院内外哪些患者我们需要经验性抗真菌治疗？ 目前社区、院内真菌感染流行现状怎样？ 哪些证据使我们认为该患者可能是真菌感染？危险因素、临床症状、实验室检查生物标记细菌学检查、辅助检查、组织学证据？这些结果可信吗？,侵袭性肺曲霉病念珠菌血症,肺曲霉流行病学,Isolation of Aspergillus spp. from the respiratory tract in critically
8、ill patients: risk factors, clinical presentation and outcome Critical Care 2005, 9:R191-R199,Methods 超过9个月 73 intensive care units (ICUs)多中心前瞻 ICU stay longer than 7 days的患者Results 总数1756 病人, 检出Aspergillus spp 36例（2%）.定植死亡率50%，感染死亡率 80% Conclusion 重症患者有感染且气道分泌物检出曲霉应该考虑治疗,重症患者 IPA预后,2006-2008意大利38家I
9、CU前瞻研究IPA（临床诊断）发生率6.31 per 1000 admissions； candidaemia 10.08 per 1000 admissions；30天死亡率前者明显高于后者63% vs. 46% 早前更有报道接近100%,Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (20062008) ；2011 Mycoses 55, 7379 Diagnosing invasive fungal diseas
10、e in critically ill patients Critical Reviews in Microbiology, 2011; 37(4): 277312,长期用皮质激素的COPD 高剂量全身使用激素3weeks (e. g. prednisone equivalent 20 mg/day) 慢性肾衰RRT Liver cirrhosis/acute hepatic failure 近期溺水 Diabetes mellitusR. J. Trof et al Management of invasive pulmonary aspergillosis in nonneutropeni
11、c critically ill patients Intensive Care Med (2007) 33:16941703,ICU肺曲霉病高危因素,Sources of Infection?Aspergillus species are found in : Soil Air; spores may be inhaled Water / storage tanks in hospitals etc Food Compost and decaying vegetation Fire proofing materials Bedding, pillows Ventilation and air
12、 conditioning systems Computer fans,Aspergillus spores,曲霉分类,曲霉属约有175个种,但仅一小部分与人类疾病相关： Aspergillus fumigatus烟曲霉 Aspergillus flavus黄曲霉Aspergillus terreus土曲霉 Aspergillus niger黑曲霉 Aspergillus nidula构巢曲霉,曲霉致病机制,曲霉无处不在 曲霉分生孢子很易播散，通过空气传播 曲霉条件致病：过敏反应、侵袭 机体条件：皮肤粘膜屏障破坏及中性粒细胞、巨噬细胞功能受损,肺曲霉病理&临床,血管侵袭性 aspergillo
13、sis 气道侵袭性aspergillosis 半侵袭性 Aspergillosis 曲霉肉芽肿(aspergilloma) Allergic bronchopulmonary aspergillosis,Spectrum of Pulmonary Aspergillosis: Histologic,Clinical, and Radiologic Findings RadioGraphics 2001; 21:825837,Angioinvasive aspergillosis,Angioinvasive aspergillosis in a 42-year-old man with acut
14、e myelogenous leukemia.(a) Chest CT scan (lung window) reveals a 2-cm nodular lesion with a wide halo of ground-glass attenuation representing adjacent hemorrhage.(b) Photograph of a cut section of the lung demonstrates a rounded tan nodule, a finding that is consistent with pulmonary infarction. (c
15、) Low-power photomicrograph (original magnification, 40;hematoxylin- eosin stain) shows vascular invasion by Aspergillus species (arrows).,In summary, the CT halo sign may be seen with awide spectrum of pulmo- nary diseases; it is most commonly associated with hemorrhagic nodules andis more rarely a
16、ssociated with tumor cell or inflam- matory infiltrate. Notwith- Standing this wide spect- rum of associated diseases, the CT halo sign is a useful diagnostic clue in the app- ropriate clinical setting and may be the first evidence of pulmonary fungal infec- tion.,Invasive aspergillosis in a 6-yearo
17、ld girl with neutropenia and acute lymphocytic leukemia. (a) Frontal chest radiograph shows a lingular infiltrate. (b) Frontal chest radiograph obtained 1 week later shows interval evelopment of at least two air crescent signs (arrowheads), which coincided with recovery of the patients white blood cell count.,
