1、倪語星上海交通大學醫學院附屬瑞金醫院臨床微生物科條件致病菌 致病性雙相真菌 l念珠菌 組織胞漿菌l曲霉 球孢子菌l隱球菌 芽生菌l接合菌 馬內菲青霉l鐮刀菌 孢子絲菌l暗色真菌l酵母菌l毛孢子菌l枝頂孢霉侵襲性真菌病(IFD)主要包括：l念珠菌病l隱球菌病l侵襲性曲霉病l廣譜抗生素應用l入住ICUl血液系統腫瘤病人（粒缺、骨髓移植）l器官移植lHIV感染l應用皮質激素l糖尿病l靜脈插管美國美國49家醫院血液分離病原菌及死亡率家醫院血液分離病原菌及死亡率次序次序病原菌病原菌菌株菌株數數% 死亡率死亡率(%)1凝固酶陰性葡萄球菌凝固酶陰性葡萄球菌3,908 31.9212金黃色葡萄球菌金黃色葡萄球

2、菌1,928 15.7 253腸球菌腸球菌1,354 11.1 324念珠菌念珠菌934 7.6 405大腸艾希菌大腸艾希菌7005.7 246克雷伯菌克雷伯菌6625.4277腸桿菌屬腸桿菌屬5574.5288假單胞菌屬假單胞菌屬5424.4339沙雷菌屬沙雷菌屬1771.42610草綠色鏈球菌草綠色鏈球菌1731.423Edmond et al. Clin. Infect. Dis. (1999). 29:239-24478 79 80 81 82 83 84 85 86 87 88 89 90 91 9202468Aspergillus spp.Candida spp.All other

3、Prevalence at Autopsy %Prevalence of invasive aspergillosis at necropsy at JW Geothe University Hospital,Frankfurt,Germany(Lancet ,2000;335:2076)54.84%12.9%3.23%9.68%19.35%國內西南醫院尸解資料，國內西南醫院尸解資料，(1971-2000)，郝飛教授提供，郝飛教授提供CryptococcusMucorCandidaAll others侵襲性真菌病的流行病學特點l危險因素不斷增多，發生率逐年增高趨勢，確切資料有待收集整理l白念珠

4、菌仍然是最常見臨床分離致病菌 l非白念珠菌增加（帶來的問題）l曲霉已成為重要的致死真菌l形態學檢查：經驗？陽性率？l培養+鑒定：時間長，敏感性？l血清學檢查：敏感性？特異性？l分子生物學檢查：標準化？GM試驗：試驗：血漿、血清、血漿、血清、BAL、胸水、胸水、CSF，用于曲霉檢測；，用于曲霉檢測；G試驗試驗: 用于曲霉、念珠菌檢測，用于曲霉、念珠菌檢測，對隱球菌、接合菌無意義；對隱球菌、接合菌無意義；乳膠凝集試驗乳膠凝集試驗: 檢測隱球菌；檢測隱球菌；Marr and Leisenring Clin Infect Dis 2005; 41:S381Musher et al. J Clin Mi

5、crobiol 2004: 42(12): 5517-22敏感性敏感性 (%)特異性特異性 (%)陽性預測陽性預測 (%) 陰性預測陰性預測 (%)血清血清47937382BAL8510010088Becker et al. Br J Haematol 2003; 121: 448u可作為推定診斷的標準可作為推定診斷的標準;uGM: 檢測半乳甘露聚糖，對檢測半乳甘露聚糖，對曲霉曲霉感染診斷特感染診斷特異性強，假陽性反應可以在青霉菌屬中出現；異性強，假陽性反應可以在青霉菌屬中出現；部分含青霉烷砜衍生物的抗菌藥物可以誘發部分含青霉烷砜衍生物的抗菌藥物可以誘發陽性反應；陽性反應；uG試驗試驗: 檢測

6、檢測(1,3)-D-葡聚糖，在很多真菌中葡聚糖，在很多真菌中都可以出現陽性反應，但在隱球菌、接合菌、都可以出現陽性反應，但在隱球菌、接合菌、毛霉、根霉呈陰性反應；毛霉、根霉呈陰性反應；Prospective utility of (1-3)-B-D-Glucan (BG), galactomannan (GM) and anti-Candidaalbicans germ tube antibodies (CAGT) for the diagnosis of invasive fungal disease (IFD) in haemato-oncology adult patientsA. Al

7、hambra1, M.S. Cutara2, J.M. Moreno1, A. Del Palcio Perez-Medel1, I. Moragues3, J.Pontn3, A. Del Palacio11Hospital Universitario Doce de Octubre, MADRID, Spain 2Hospital Universitario SeveroOchoa, LEGANES, Spain 3Universidad del Pais Vasco, BILBAO, SpainInvasive Candidiasis S SP PPV NPVCAGT (%) 57 93

8、 44 96BG (%) 77 86 39 97Invasive Aspergillosis S SP PPV NPVGM (%) 92 94 73 98BG (%) 57 84 42 91CONCLUSIONS The incidence of IFD correlated directly and significantly (x2 p=0.0005) with risk stratification group: highest proportion in the high-risk group.Since all the biomarkers have inherent limitat

9、ions, a better diagnosis yield is achieved combining the biomarkers. All three biomarkers share high negative predictive value and can exclude reasonably IFD in haematology adult patients treated with wide spectrum antifungals.Evaluation of two serologic test for diagnosis invasive AspergillosisC. C

10、astro, A. Romero, A. Aller, T. Gonzalez, A. Gonzlez, E. Martn-MazuelosH. U. Valme, SEVILLA, SpainA total of 236 sera from 51 patients in risk of IA were tested for GM using Platelia Aspergillus kit (Bio Rad, France) which 36 sera (10 patients) were tested for BG also using Fungitell kit (Associates

11、of Cape Cod., USA). Patients were attended at the University Hospital of Valme from Seville from January of 2008 to December 2008. Patients with GM index 0.5 in two consecutive samples have been marked as GM positive and samples with results 80pg/ml were marked as BG positive. All GM positive patien

12、ts were classified according to EORTC/MSG criteria (2008) for probability of IA.lFrom 51 patient studied, 16 of them showed at least one positive specimen (33 sera). lOnly 6 patients showed two consecutive positive results (0.5 GM test) and they show clinical signs or microbiological criteria for AI

13、 proven (3 patients) and probable (3 patients). lThe BG assay were used in parallel with GM in 36 sera which 26 showed positive result from 9 patients, (3 with AI proven and 6 AI probable). l3 patients showed positive results before for BG test ( 3,5 days) and 6 patients presented simultaneously bot

14、h antigens. Never the GM test was the first serological test to show a positive result.lG試驗陽性的9名患者中，G試驗單獨陽性的有3個病人，兩種抗原同時陽性有6個病人，未出現單獨GM試驗陽性的情況。ConclusionCalculating significant sensitivity for both detection methods was not feasible due to a low number of proven/probable AI. BG detection showed posi

15、tive results before GM test and present the great advantage to be a “panfungal”antigen. BG detection should be used with other techniques for detection of invasive Aspergillosis infections. 病例選擇病例選擇 深部真菌感染患者深部真菌感染患者35例，年例，年 齡齡1288歲，來自我院歲，來自我院2004年年1月到月到5月住院患月住院患者，均經培養證實存在深部真菌感染，感染者，均經培養證實存在深部真菌感染，感染

16、部位包括呼吸道、泌尿道、血液及靜脈插管部位包括呼吸道、泌尿道、血液及靜脈插管引起的系統性感染。正常健康對照組引起的系統性感染。正常健康對照組30人，人，來自我院健康查體者。來自我院健康查體者。第四軍醫大學第四軍醫大學 l正常對照組血漿1-3-D葡聚糖含量最高為7.29 pg/ml ，最低為0.45 pg/ml，平均值為2.832.57pg/ml；l深部真菌感染組血漿1-3-D葡聚糖含量最高為168.9 pg/ml，最低為14.93pg/ml，平均值為54.0636.13 pg/ml。l經SPSS統計軟件T-檢驗分析，對照組與深部真菌感染組1-3-D葡聚糖平均值差異非常顯著（t=7.741,P0.001）。 l入選的深部真菌感染患者均經細菌培養證實為念珠菌感染，包括白色念珠菌23株、熱帶念珠菌8株、季也蒙念珠菌1株、克柔念珠菌1株和光滑球擬假絲酵母菌2株，無隱球菌感染。l如以10 pg/ml為cutoff值，則陽性率為100%; 以20 pg/ml為cutoff值，則陽性率為91.4。l葡聚糖檢測可在擬診早期為臨床醫生提供機體是否感染真菌的可靠信息，因此葡聚糖含量檢測不失為一種實用的真菌感染早期診斷方法。l使用青霉素類l加酶抑制劑l香菇多糖等會引起假陽性！PCR 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1