临床医生如何看待真菌感染与定植 ppt课件

1、111/9/2021 doctor xiong临床医生如何看待真菌感染与定植211/9/2021 doctor xiong11/9/2021内容提要 侵袭性曲霉感染误诊分析 念珠菌定植问题腹腔念珠菌感染诊治问题123311/9/2021 doctor xiong真菌概述酵母菌属酵母菌属曲霉菌属曲霉菌属深部真菌感染深部真菌感染念珠菌属隐球菌属411/9/2021 doctor xiong常见的侵袭性念珠菌感染部位511/9/2021 doctor xiongl 定植不是感染l 定植不是与感染没有一点关系定植感染污染：外来物质或能量的作用，导致生物体或环境产生不良效应的现象。定植：各种微生物经常从

2、不同环境落到人体，并能在一定部位定居和不断生长、繁殖后代，这种现象通常称为“定植”。感染：是指细菌、病毒、真菌、寄生虫等病原体侵入人体所引起的局部组织和全身性炎症反应。611/9/2021 doctor xiong侵袭性真菌病确诊(proven)诊断标准正常无菌部位并不包括所有与外界相通的器官，即呼吸道、泌尿生殖道、消化道等，因为上述器官是念珠菌属常见的定植部位。念珠菌病诊断与治疗：专家共识. 中国感染与化疗杂志.2011；11（2）：81-95711/9/2021 doctor xiong 念珠菌属于类酵母样菌，有酵母相和菌丝相p 酵母相为芽生孢子，在无症状寄居及传播中起作用，不引起症状p

3、菌丝相为芽生孢子伸长呈假菌丝，大量繁殖，侵袭组织能力加强，出现临床症状 需要注意的是，念珠菌中的光滑念珠菌不能产生假菌丝/菌丝，所以，临床不能因为“镜检念珠菌处于酵母相”就排除感染酵母相菌丝相念珠菌多为假菌丝念珠菌镜检假菌丝或菌丝811/9/2021 doctor xiong colonization with candida has been identified as an important risk factor with high predictive value for development of invasive disease (particularly with incre

4、asing numbers of colonized sites). 念珠菌定植 侵袭性念珠菌感染定植菌争议的焦点invasive candidiasis in the intensive care unit. crit care med 2006. 34(3):857-863eggimann p，garbino j，pittet depidemiology of candida species infections in critically ill non-immunosuppressed patientslancet infect dis，2003，3(11)：685-702pk911/

5、9/2021 doctor xiongp 多部位多部位念珠菌定植是发生侵袭性念珠菌感染的独立危险因素独立危险因素。p 念珠菌定植后导致侵袭性感染的途径途径可能有： 破坏胃肠道黏膜屏障入血； 从中心静脉导管入血， 从局部感染蔓延至全身。定植与感染的关系lipsett pasurgical critical care=fungal infections in surgical patientscrit care med，2006，34(9 suppl)：s215-224约有5086的重症患者发生念珠菌定植，但临床有530发展成严重侵袭性念珠菌感染。1011/9/2021 doctor xionga

6、lthough colonization does not define infection, these data support the well-known role of candida colonization as a key factor in the decision to start early antifungal treatment for icu patients.a bedside scoring system (“candida score”) for early antifungal treatment in nonneutropeniccritically il

7、l patients with candida colonization. crit care med 2006. 34(3):730-737.定植与感染的死亡率1111/9/2021 doctor xiongs.s. magill et al. diagnostic microbiology and infectious disease 55 (2006) 293 301进展为ic的百分比uthe anatomic site of candida colonization in 182 surgical intensive care unit (sicu) patients who part

8、icipated in a randomized trial of fluconazole to prevent candidiasis.ua total of 2851 surveillance fungal cultures collected from 5 anatomic sites were analyzed.usurveillance fungal cultures of particular anatomic sites may help differentiate patients at higher risk of developing ic from those at lo

9、w risk.p=0.02p=0.04p=0.0113.2%2.8%8.0%1.2%8.4%0.0%定植可进展为侵袭性念珠菌病1211/9/2021 doctor xiongu 对于怀疑系统性念珠菌感染的患者，应同时进行痰(或其他气道分泌物)、尿、胃液、粪(或直肠拭子)、口咽拭子5个部位的念珠菌定量培养。u 口咽和直肠拭子念珠菌只要1 cfu，胃液、尿105 cfu /l，痰107 cfu/l就认为念珠菌定植阳性。念珠菌定植指数(ci)pittet d，monod m，suter pm，et a1candida colonization and subsequent infections in

10、 critically ill surgical patientsann surg，1994，220(6)：7517581311/9/2021 doctor xiongu口咽和直肠拭予念珠菌102 cfu，胃液、尿、痰108 cfu/l才能判定念珠菌定植阳性，如ci0.5或cci0.4就认为有侵袭性念珠菌感染的可能。校正念珠菌定植指数(cci)piarroux r，grenouillet f，balvay p，et a1assessment of pre-emptive treatment to prevent severe candidiasis in critically ill surg

11、ical patientscrit caremed，2004，32(12)1244324491411/9/2021 doctor xiong念珠菌指数(cs)u将患者的危险系数相加，就得到该患者的cs。u研究结果显示，cs2.5时诊断侵袭性念珠菌感染的敏感性为81，特异性为74。cs=0.908肠外营养支持+0.997手术+1.112cci+2.038严重脓毒症。lean c， ruizsuntans s， saavedra p，et a1a bedside scoring system (”candida score”)for early antifungal treatment in no

12、nneutropenic critically i11 patients with candida colonizationcrit care med，2006，34(3)：7307371511/9/2021 doctor xiongp in addition to multifocal candida species colonization, three other risk factors were found to be significant predictors of proven candidal infection in the logistic regression mode

13、l: use of total parenteral nutrition； surgery on icu admission； clinical manifestations of severe sepsis.score1121a bedside scoring system (“candida score”) for early antifungal treatment in nonneutropenic critically ill patients with candida colonization. crit care med 2006. 34(3):730-737.1611/9/20

14、21 doctor xiong we shall only need the presence of sepsis and any one of the three other remaining risk factors or the presence of all of them together except sepsis in order to consider starting antifungal treatment for one particular patient.logistic regression modela bedside scoring system (“cand

15、ida score”) for early antifungal treatment in nonneutropenic critically ill patients with candida colonization. crit care med 2006. 34(3):730-737.1711/9/2021 doctor xiong2008年亚太危重病论坛也指出，重症高危患者如同时具有高度念珠菌定植应予以抗念珠菌治疗，同时亦应考虑局部区域的真菌流行病学资料。要正确看待ci、cci、cshsueh pr，graybill jr，playford eg，et a1consensus stat

16、ement on the management of invasive candidiasia in intensive care units in the asiapacific regionint j antimicrob agents，2009，34(3)：205209u使用定植指数推测侵袭性念珠菌感染诊断只是一种“可能性”诊断。u对于可能发生侵袭性念珠菌感染的高危患者实施动态监测，一旦病情 变化应及时给予抢先治疗，既要防止发生进一步的侵袭性念珠菌感 染，降低病死率，又要避免不必要的抗真菌药物临床应用，以降低患 者医疗费用和抗生素附加损害。1811/9/2021 doctor xiong

17、ueggimann等更明确地为抢先治疗下定义，即对具有多个侵袭性念珠 菌感染高危因素且ccl0.4的脓毒症患者早期给予抗念珠菌治疗。定植菌抢先治疗的定义u同时他认为实施抢先治疗可降低外科重症患者侵袭性念珠菌感染确诊 病例的发生和降低病死率。eggimann p，garbino j，pittet depidemiology of candida species infection in critically ill non-immunosuppressed patientslancet infect dis，2003，3(11)：6857021911/9/2021 doctor xiong痰培养

18、阳性的临床意义？u 如果患者存在明显的高危因素，有肺部感染的临床表现又不能用其他 病原菌感染解释，血清真菌感染标志物（如g试验）阳性，此时痰培 养念珠菌为唯一病原体且为反复培养阳性或为纯培养，可以作为针对 念珠菌诊断性或经验性治疗的依据，至少提醒临床医生应提高警惕， 特别是除肺外还有其他部位也分离到念珠菌时。u 怀疑念珠菌肺炎的患者在呼吸道标本检测的同时应做血液真菌培养，如 血培养分离出念珠菌，且与呼吸道分泌物培养结果相一致，有助于念珠 菌血症继发肺念珠菌病或肺炎合并念珠菌血症的诊断。2011/9/2021 doctor xiong11/9/2021内容提要 侵袭性曲霉感染误诊分析 念珠菌定植

19、问题腹腔念珠菌感染诊治问题123 1 32111/9/2021 doctor xiong吕新生，腹部外科2004年第17卷第3期 腹腔感染腹腔感染定义2211/9/2021 doctor xiong曹彬等. 侵袭性念珠菌院内感染的流行病学调查. 中华医学杂志 2008;88(28)1970-1973念珠菌腹腔感染位居第二位2311/9/2021 doctor xiong常见的腹腔念珠菌感染2411/9/2021 doctor xiong腹腔念珠菌感染的高危因素pimmunodeficiency.pprolonged exposure to antibiotics.pupper gi tract

20、 perforations (one should therefore always take into account the possibility of candida involvement in patients experiencing tertiary peritonitis) .1.sotto a, lefrant jy, fabbro-peray p, et al. evaluation of antimicrobial therapy management of 120 consecutive patients with secondary peritonitis. j a

21、ntimicrob chemother 2002; 50:569576.2.charles pe. multifocal candida species colonization as a trigger for early antifungal therapy in critically ill patients: what about other risk factors for fungal infection? crit care med 2006; 34:913914.2511/9/2021 doctor xiongphilippe montravers et al. candida

22、 as a risk factor for mortality in peritonitis. crit care med. 2006;34(3):646-52p 一项多中心、回顾性对照研究，在教学及非教学医院的17个icu进行 其中确诊院内腹膜炎的患者中，腹水病原菌分离率以白念最多腹水中病原菌分离率(%)白念珠菌n=39肠杆菌科n=31肠球菌n=19厌氧菌n=11大肠杆菌n=15白念是腹腔感染的主要致病真菌2611/9/2021 doctor xiongp胃肠道是念珠菌寄居的主要场所 大量的念珠菌定植 致病 p在空腔脏器穿孔或肠壁手术时，念珠菌可渗漏到腹腔多数可被腹膜迅速清除在一些病人中会进

23、行腹膜播种，可导致腹腔念珠菌感染，也可播散 至血流和腹部之外的组织和器官thierry calandra et al. clinical trials of antifungal prophylaxis among patients undergoing surgery. cid. 2004;39 (4):s185-192腹腔侵袭性念珠菌感染的发生机制2711/9/2021 doctor xiong分离的念珠菌在腹腔感染中起致病作用争议p 目前大量的研究显示 念珠菌腹腔感染死亡率高达：27%77% 强烈主张抗真菌的抢先治疗（经验治疗）thierry calandra et al. clinic

24、al trials of antifungal prophylaxis among patients undergoingsurgery. cid. 2004;39 (4):s185-192对腹腔念珠菌感染的看法腹腔分离的念珠菌是“无辜的牵涉者”2811/9/2021 doctor xiong在271例 icu腹膜炎患者中，83例念珠菌腹膜炎患者dupont h,et al. arch surg. 2002 dec;137(12):1341-6.死亡率(%)n=83n=188念珠菌腹膜炎非念珠菌腹膜炎11%念珠菌腹膜炎死亡率高2911/9/2021 doctor xiong比利时的ghent

25、大学医院感染疾病中心的icu，对1995.1-2002.12入住icu的急性重症胰腺炎胰腺坏死感染的患者46例进行分析，分析真菌感染发生率jan j. de waele et al. cid 2003;37(7):208-213胰腺真菌感染的真菌菌种分布:白念珠菌为主sap真菌感染几乎全部为念珠菌3011/9/2021 doctor xiongsap合并念珠菌感染与细菌感染的不同am j gastroenterol. 2009 aug;104(8):2065-70. p 1992-2001，207 例sap患者p 52例确认有细菌感染（ibi），其中30例 (15%) 合并真菌感染（ifi），

26、 7例原发，23例继发ifi 57.7%3111/9/2021 doctor xiongantibiotic 40%100%tpn 42%85%5%68%am j gastroenterol. 2011 jul;106(7):1188-92. sap合并腹腔念珠菌感染：荟萃分析3211/9/2021 doctor xiongplocal treatment debridement or necrosectomy minimization of intraoperative hemorrhage maximization of postoperative removal of retroperi

27、toneal debris and exudatespsystemic antifungal treatment needs to be started early in the course of the disease.am j gastroenterol. 2011 jul;106(7):1188-92防治sap合并腹腔念珠菌感染的措施3311/9/2021 doctor xiong腹腔念珠菌脓肿腹腔脓肿p隔下脓肿 原发性通过血流传播所致 继发性为腹腔内化脓性感染的并发症，其中最常见的为急性阑尾炎穿孔、胃十二指肠溃疡穿孔以及肝胆系统的急性炎症，占隔下脓肿的60%85%p盆腔脓肿p肠袢间脓

28、肿3411/9/2021 doctor xiong念珠菌腹腔感染中腹腔脓肿占：36.8%thierry calandra et al. clinical significance of candida isolated from peritoneum in surgical patients. the lancet.1989;december 16.p1437-1440腹腔念珠菌脓肿发生率3511/9/2021 doctor xiong体会1. 诊断问题p社区获得性腹腔感染重症型（严重病理生理指标紊乱、高龄、免 疫抑制）与医院获得性腹腔感染的病原菌可能为真菌。p继发性腹膜炎经常规外科处理后，腹

29、腔感染症状缓解48h后复发 或腹腔感染症状持续存在时，病原菌可能为真菌感染。p高危腹腔感染此前应用过抗生素的病人，真菌感染的可能性更大。p腹腔感染部位取得的标本应足以代表临床感染。pg试验可以作为参考。3611/9/2021 doctor xiong体会2. 治疗问题p如果腹腔脓液培养结果示念珠菌生长，对重度社区获得性或医院 获得性感染病人推荐进行抗真菌治疗。p如果分离得到白念珠菌，推荐使用氟康唑。p对氟康唑耐药的念珠菌，推荐棘白菌素类抗菌药（如卡泊芬净、 米卡芬净）。p危重病人的初期治疗推荐棘白菌素，不推荐三唑类抗菌药。p由于两性霉素b不良反应较大，初期不推荐应用两性霉素b。p如果抗感染治疗

30、47d后，病人仍有持续或复发的腹腔感染征 象，应进行ct或超声等影像学检查明确诊断，并行经验性抗真菌 治疗。3711/9/2021 doctor xiong11/9/2021内容提要 侵袭性曲霉感染误诊分析 念珠菌定植问题腹腔念珠菌感染诊治问题1233811/9/2021 doctor xiongmeersseman et al. clinical infectious diseases 2007; 45:20516pcopd合并呼吸衰竭入住icu，接 受皮质激素治疗p胸片：两肺局灶性渗出、模糊、右 侧胸腔积液pbal培养：流感嗜血杆菌（+）、 霉菌（-）p血清gm（-）pbal gm 2.6

31、ng/mlp尸检：ipa例1. aecopd呼吸衰竭患者3911/9/2021 doctor xiongmeersseman et al. clinical infectious diseases 2007; 45:20516p肝移植受体者p胸片：右侧片状实变影，类似肺部感染pbal：细菌、霉菌（-）p血清gm（-）p尸检：播散性曲霉例2.肝移植患者4011/9/2021 doctor xiongmeersseman et al. clinical infectious diseases 2007; 45:20516p急性粒细胞白血病骨髓移植后接受高 剂量抗排异治疗4月p胸片：右侧肺片状渗出、

32、胸腔积液pct：右侧肺局部实变影伴有空洞、 有液平；第4、5肋骨破坏；左侧肺锲 型实变影p胸腔积液培养：烟曲霉例3.骨髓移植患者4111/9/2021 doctor xiongmeersseman et al. clinical infectious diseases 2007; 45:20516p晚期糖尿病肾移植2月p胸片及ct：两下肺斑片状阴影伴空 洞、右侧胸腔积液p血清gm 0.1ng/ml、pbal gm 5.7ng/mlp经支气管活检：烟曲霉p死于三尖瓣心内膜炎（曲霉）例4.肾移植患者4211/9/2021 doctor xiong这些病人如果没有活检或尸检的话，你会诊断侵袭性曲霉感

33、染吗？4311/9/2021 doctor xiongipa 误诊的原因p the diagnosis of ipa in non-neutropenic critically ill patients is difficult signs and symptoms are non-specific.p a positive result of a culture of a respiratory specimen or positive findings of a direct microscopic examination only one-half of patients with ip

34、a. p the predictive value of a positive culture result depends largely on whether the patient is immunocompromised and ranges from 20% to 80%.1.trof et al. intensive care med 2007;33:16947032.hope ww, walsh tj, denning dw. laboratory diagnosis of invasive aspergillosis. lancet infect dis 2005; 5:609

35、22.3.tarrand jj, lichterfeld m,warraich i, et al. diagnosis of invasive septate mold infections: a correlation of microbiological culture and histologicor cytologic examination. am j clin pathol 2003; 119:8548.4411/9/2021 doctor xiongmeersseman et al. clinical infectious diseases 2007; 45:20516ipa的危

36、险因素4511/9/2021 doctor xionggm 抗原的敏感性与特异性p correlates with fungal burden in animal and clinical studies sensitivity and specificity limitations in non-neutropenic patients (sot) detected in csf, bronchoalveolar lavage (bal) fluidsensitivity (%)specificity (%)hsct8992liver transplant55.6 93.9 98.5lung

37、 transplant95304611/9/2021 doctor xiongp serologic testing techniques of galactomannan (gm) hold promise for patients with hematologic malignancy.p gm studies of neutropenic patients have revealed high rates of sensitivity (67%100%) and specificity (86%99%). p however, in a retrospective observation

38、al study of a medical icu population, serum gm was elevated in only 53% of patients with ia. p detection of serum gm is probable not a sensitive marker for ia (especially in non-neutropenic patients). meersseman et al. clinical infectious diseases 2007; 45:20516gm试验在ipa的价值4711/9/2021 doctor xiongp g

39、m has to be stressed that the available data from patients with (haematological) malignancies and after solid organ transplantation can not be extrapolated to the critically ill patient in general. p in the meantime, due to lack of more reliable, non-invasive diagnostic tests, the gm assay could be

40、used as an additive tool in the diagnostic work-up of ipa.trof et al. intensive care med 2007;33:1694703gm试验可以作为ipa的辅助诊断4811/9/2021 doctor xiongipa高风险病人的诊治策略monique a s h mennink-kersten, j peter donnelly, and paul e verweijthe lancet infectious diseases vol 4 june 2004possibleprobableproven4911/9/2

41、021 doctor xiongp 38 patients probable (n = 28) proven (n = 10) . 37% patients 2 risk factors for ia. p all probable ia were diagnosed by bal. p proven ia was reached by positive histopathologic and culture results of samples autopsy (n = 4) percutaneous (n = 3) transbronchial biopsy (n = 3).a. hida

42、lgo et al. / european journal of radiology 71 (2009) 5560hrct与gm的相关性5011/9/2021 doctor xionghrct 分类p airway invasive aspergillosis 气道侵袭性曲霉病 aspergillus bronchiolitis （“tree-in-bud” pattern） aspergillus bronchopneumonia（air-space consolidation） p angioinvasive aspergillosis 血管侵袭性曲霉病 “halo” of ground-

43、glass “air-crescent sign”1.logan pm, primack sl, miller rr, muller nl. invasive aspergillosis of the airways: radiographic, ct, and pathologic findings. radiology 1994;193:3838.2. franquet t, muller nl, gimenez a, guembe p, de la torre j, bague s. spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic signs. radiographics 2001;21:82537.5111/9/2021 doctor xiong气道侵袭性曲霉病a. hidalgo et al. / european journal of radiology 71 (2009) 5560gm: 0.70.9gm: 0.61.05211/9/2021 doctor xiong血管侵袭性曲霉病a. hidalgo et al. / european journal of radiology 71 (2009) 5