真菌病的早期诊断-课件.pptVIP

* 第8张幻灯片 作为棘白菌素的一种，卡泊芬净是这类独特的抗真菌药物中第一个面世的产品。11 这是一种抑制细胞壁?-(1,3)-D-葡聚糖合成的新型抑制剂，特异性作用于真菌细胞膜，对人类细胞无影响11,18 ?-(1,3)-D-葡聚糖对于念珠菌属细胞壁的完整性是至关重要的11,18 通过特异性抑制?-(1,3)-D-葡聚糖合成，卡泊芬净破坏真菌细胞壁的完整性（通透性），导致细胞溶解11,12,18,19 卡泊芬净以真菌细胞壁为作用靶位的特异性作用机制(MOA) 优于两性霉素B，后者通过与甾醇结合，同时增加真菌和人类细胞壁的通透性20 卡泊芬净的作用机制优于氮唑类，前者导致真菌溶解，而后者作用于麦角固醇合成，改变真菌细胞膜，最终仅能抑制真菌20 * * * GM试验可更早的排除患者发生侵袭性曲霉感染。 对中性粒细胞减少患者而言，GM检测曲霉的敏感率为89.7-94.4%,特异性高达94－98.8％；88.8%的患者GM检测阳性出现在初始经验性抗真菌治疗前平均6天，由此显示出抗原检测-GM试验(半乳甘露聚糖)对曲霉感染具有重大诊断价值。 * * The volume of distribution at steady state for voriconazole is estimated to be 4.6 L/kg, suggesting extensive distribution into tissues.1 VFEND? effectively penetrates infected organs and tissues, including the lungs, brain, and cerebrospinal fluid (CSF). The lungs are the most common sight of invasive aspergillosis infections.2,3 In a prospective, observational study of lung transplant patients receiving oral voriconazole prophylaxis, the total (free and protein-bound) voriconazole concentration in pulmonary epithelial lining fluid (ELF) exceeded that in plasma in all patients studied; the average ELF-to-plasma ratio was 11 (±8), indicating substantial penetration of drug into the lungs.2 Until recently, the mortality of central nervous system (CNS) aspergillosis exceeded 90%, with poor CNS penetration of antifungal drugs contributing to this poor prognosis.4 Clinical evidence indicates that voriconazole penetrates well into the CNS. In a study in immunocompromised patients, CSF and plasma concentrations of voriconazole were measured 1 to 10 hours after administration; CSF concentrations ranged from 0.08 μg/mL to 3.93 μg/mL, and the ratio of CSF to plasma concentration ranged from 0.22 to 1.0 (median 0.46).5 In a woman being treated for rhinocerebral aspergillosis, voriconazole levels in brain tissues were found to exceed those in plasma by 2- to 3-fold.5 Voriconazole has been used successfully in cases of CNS aspergillosis. In one report, two patients with cerebral aspergillosis achiev