郑州2-真菌精品.pptVIP

* * So if we set the breakpoint for Candida and echinocandins closer to the ECVs for most species, say at 0.25, we’d either bisect or miss the entire MIC distribution for C. parapsilosis—and we know from existing clinical trials that C. parapsilosis clinical response rates to echinocandins have been in the 70% range, and again have insufficient data upon which to say their clinical response to echinocandins in likely to be worse than other species. So we may be headed for species specific echinocandin breakpoints. C. guilliermondii is another species which demonstrates these elevated echinocandin MICs. * * We determined the in vitro activities of anidulafungin, caspofungin, and micafungin against 526 isolates of Aspergillus spp. (64 A. flavus, 391 A. fumigatus, 46 A. niger, and 25 A. terreus isolates) collected from over 60 centers worldwide from 2001 through 2007. Susceptibility testing was performed according to the CLSI M38-A2 method. All three echinocandins—anidulafungin (50% minimum effective concentration [MEC50], 0.007ug/ ml; MEC90, 0.015ug/ml), caspofungin (MEC50, 0.015ug/ml; MEC90, 0.03 g/ml), and micafungin (MEC50, 0.007ug/ml; MEC90, 0.015ug/ml)—were very active against Aspergillus spp. More than 99% of all isolates were inhibited by 0.06ug/ml of all three agents 感染途径： 吸入空气中的孢子，此为主要途径； 创伤性皮肤接种； 　　 吃进带菌食物，经肠道播散全身引起感染 * 主要累及中枢神经系统，也可以累及肺部 仅新生隐球菌及其变种具有致病性 Kethireddy S, et al. Drug Metab Toxicol. 2007;3(4):573-81 CNS受累发病率 死亡率 隐球菌病 67-84% ＜1% 侵袭性念珠菌病 3-64% 11-67% 侵袭性曲霉病 4-6% 80-90% 吸入空气中的孢子 吸入空气中的孢子 在体内能逃避免疫追杀： 隐球菌抗原能够抑制或下调体液与细胞免疫反应 隐球菌荚膜多糖可封闭吞噬细胞的识别系统，从而抑制吞噬作用 荚膜物质也可抑制趋化反应 易侵犯中枢神经系统的原因： 脑脊液中缺乏抗体； 脑脊液中缺乏补体激活系统； 脑脊液中的多巴胺有利于隐球菌生长 注：荚膜作为新生隐球菌毒力的主要决定因素，有抵抗吞噬和下调免疫反应的双重作用 在肺部环境中，新生隐球菌可迅速合成荚膜，使肺泡巨噬细胞对其摄取，吞噬能力减弱 何礼贤 等.《侵袭性肺真菌病影像学图集》 临床常见病原真菌：念珠菌、曲霉菌、隐球菌 直接镜检与培养是鉴别真菌感染的经典方法 念珠菌感染常常为内源性，致血流感染，易引起播散； 曲霉菌具有强烈的嗜血管特性，主要侵犯肺部； 隐球菌能逃避免疫攻击，在肺部常隐匿起病，易侵犯中枢神经系统 五、抗真菌药物的临床应用 抗真菌药物分类 多烯类 两性霉素Ｂ及其脂质基制剂、制霉菌素、灰黄霉素等 吡咯类 克霉唑、咪康唑、酮康唑、氟康唑、伊曲康唑、伏立康唑、泊沙康唑 氟胞嘧啶 5-氟胞嘧