右旋糖酐在注射用醋酸卡泊芬净无菌检查中的应用

目的：通过无菌方法学验证试验,建立注射用醋酸卡泊芬净的无菌检查法。方法：样品分别用0.9%无菌氯化钠溶液溶解,采用薄膜过滤法处理,每膜分别用0.9%无菌氯化钠溶液和右旋糖酐40葡萄糖注射液冲洗若干次,并在培养基中加入右旋糖酐1g,以白色念珠菌为阳性对照菌。结果：各验证菌株均能够正常生长,方法可行。结论：通过添加外源的右旋糖酐,使真菌通过利用外源的肽聚糖用于自身细胞壁的合成,从而消除了醋酸卡泊芬净的抑菌作用,建立了抗真菌药物注射用醋酸卡泊芬净的无菌检查法。     

卡泊芬净治疗心脏术后侵袭性真菌病20例临床分析

目的:探讨卡泊芬净治疗心脏术后并发侵袭性真菌感染(IFI)的疗效与安全性。方法:回顾分析我院呼吸科、心外科和急诊重症监护室(ICU),接受过卡泊芬净治疗的心脏术后合并IFI患者临床资料。结果:2005年5月至2010年12月,共有20例接受了卡泊芬净治疗。男性12例,女性8例,中位年龄65岁(23～82)岁。确诊10例,皆为念珠菌血症(白念珠菌4例,近平滑念珠菌3例,光滑念珠菌、热带念珠菌和克柔念珠菌各1例);临床诊断肺IFI 5例(念珠菌3例,曲霉2例);拟诊肺IFI 5例,病原真菌不明。冠状动脉搭桥(CABG)术8例,瓣膜手术8例,胸主动脉瘤手术2例,先天性心脏病(先心病)和马方综合征手术各1例。卡泊芬净的使用时间中位数为18(1～55)d。1例于用药当天死于心脏骤停疗效无法判断,19例可评估患者中,痊愈10例(10/19,52.6%),显效4例(4/19,21.1%),总有效率为73.7%,进步3例,无效2例。死亡6例(6/20,病死率30.0%)。治疗过程中未发现与卡泊芬净有关的不良反应。结论:卡泊芬净是治疗心脏术后并发IFI的有效安全药物,值得进一步临床验证。     

Dosing of caspofungin based on a pharmacokinetic/pharmacodynamic index for the treatment of invasive fungal infections in critically ill patients on continuous venovenous haemodiafiltration

Introduction

The study objective was to evaluate the efficacy of different dosages of caspofungin in the treatment of invasive candidiasis and aspergillosis, in relation to the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment, using modelling and Monte Carlo simulations in critically ill adult patients on continuous haemodiafiltration.

In vitro biofilm characterization and activity of antifungal agents alone and in combination against sessile and planktonic clinical Candida albicans isolates

Thirty clinical isolates of Candida albicans were collected from blood or other sterile site infections. Biofilm dry weight and metabolic activity were measured for each isolate. Planktonic and sessile antifungal susceptibilities of each isolate were determined for amphotericin B deoxycholate, caspofungin, and voriconazole. Sessile susceptibilities were determined for the combination of caspofungin/voriconazole. No significant differences in biofilm dry weight or metabolic activity were found between bloodstream and other invasive isolates. Planktonic MIC90 values and sessile MIC90 (SMIC90) values were 0.25 and 2, 0.06 and >256, and 0.5 and 2 microg/mL for amphotericin, voriconazole, and caspofungin, respectively. The SMIC90 of the combination of caspofungin/voriconazole against sessile isolates was 0.5/2 microg/mL. Therefore, the source of invasive C. albicans clinical isolates did not affect in vitro biofilm formation. Susceptibility to antifungal agents decreased when C. albicans was associated with biofilm, and the combination of caspofungin/voriconazole did not appear to provide enhanced activity compared with caspofungin alone.     

白念珠菌生物膜对卡泊芬净的敏感性研究

目的探讨新生白念珠菌生物膜对卡泊芬净的敏感性。方法建立白念珠菌生物膜模型,采用标准化念珠菌生物膜抗真菌药物敏感实验法测定白念珠菌生物膜对卡泊芬净和两性霉素B的敏感性。结果30株白念珠菌生物膜中,6株对两性霉素B敏感（SMIC80≤1μg/ml）,24株对两性霉素B耐药（SMIC80〉1μg/ml）;28株对卡泊芬净敏感（SMIC80〈16μg/ml）,2株对卡泊芬净耐药（SMIC80≥16μg/ml）。经统计学分析,就白念珠菌生物膜的对抗真菌药物的敏感性而言,卡泊芬净和两性霉素B之间有统计学意义（χ^2=32.86,P〈0.05）。结论白念珠菌生物膜对两性霉素B耐药明显,而对卡泊芬净敏感。     

Refractory pulmonary aspergillosis treated with caspofungin after heart–lung transplantation

Invasive pulmonary aspergillosis (IPA) is a serious complication of lung transplantation. Pre-mortem diagnosis is difficult and is made according to defined criteria. Most patients with a post mortem diagnosis of IPA only reach the possible or probable levels of diagnostic certainty during life. Here, we report a case of probable IPA that was refractory to conventional treatment, including amphotericin, but which responded to therapy with caspofungin. A 23-year-old man underwent heart–lung transplantation for cystic fibrosis. Ten years after transplantation he developed IPA. His condition continued to deteriorate despite treatment with itraconazole, liposomal amphotericin and flucytosine together with treatment of a concomitant infection with Pseudomonas aeruginosa. Following treatment with caspofungin there was progressive and sustained clinical and radiological improvement. No adverse reaction occurred during treatment. Caspofungin should be considered as an alternative treatment for IPA in lung transplant recipients who fail to respond to other therapy.     

New systemic antifungal drugs: mechanisms of action,drug interactions and side effects

New antifungal agents are needed to match the currently increasing rate of systemic fungal infections and the development of resistant fungal strains. This appears possible by the introduction of second generation azole antifungals which potently inhibit ergosterol synthesis, but also by a partial synthetic echinocandin analogue which acts by the suppression of the enzyme glucan synthase. Voriconazole and caspofungin have been approved for the treatment of invasive aspergillosis. Both drugs are well tolerated if contraindications and--with voriconazole--also possible drug interactions are respected. Possibly these drugs are also suitable for other severe fungal infections including systemic and oropharyngeal candidosis in the immunocompromised host.     

卡泊芬净治疗高龄多器官功能衰竭合并肺部真菌感染的临床分析

目的：探讨卡泊芬净治疗老年合并多器官功能衰竭侵袭性肺部真菌感染的安全性及疗效。方法：选取老年合并多器官功能障碍综合征侵袭性肺部真菌感染的患者24例（n=24）,根据诊断分为临床诊断病例（n=14）、拟诊病例（n=4）、疑似病例（n=6）。分别给予卡泊芬净治疗,根据侵袭性真菌感染的疗效评价标准,判定卡泊芬净对老年多器官功能障碍综合征侵袭性肺部真菌感染的有效率。同时观察该药的安全性及用药相关不良反应。结果：24例患者中,所有患者总的有效率为75.0%（18/24）,其中临床诊断病例有效率为78.6%,拟诊病例有效率为50.0%,疑似病例有效率为83.3%。各组病例治疗过程中安全性好,无一例出现严重的药物反应或治疗相关意外。结论：卡泊芬净对高龄多器官功能衰竭合并肺部真菌感染疗效确切,安全性好,值得临床推广应用。