Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

肺隐球菌病并发纵隔淋巴结结核误诊一例——病例报告及文献复习

肺隐球菌病是一种吸入隐球菌孢子而引起的肺急性、亚急性或慢性真菌病,易播散至中枢神经系统而导致隐球菌性脑膜炎,病死率和致残率高。近年肺隐球菌病的发病率呈增长趋势。肺隐球菌病的临床症状及体征、肺部影像学及实验室检查均缺乏特异性,因此极易漏诊、误诊。河北省胸科医院病理科近期会诊一例肺隐球菌病并发纵隔淋巴结结核患者,曾在外院就诊时经影像学及临床检查误诊为肺癌,术后病理误诊为肺结核,经我院会诊其病理切片及进行辅助检查(特殊染色、结核分枝杆菌核酸检测)后最终明确诊断。现结合相关文献回顾性分析其临床、影像及病理特点,以期提高其诊断水平,避免误诊误治。     

隐球菌荚膜抗原检测在隐球菌病中的诊断价值

隐球菌病是由隐球菌感染人体引起的一种侵袭性真菌病,是艾滋病患者及实体器官移植者中常见的感染和致死原因.10年来,隐球菌病的诊断方法 已从真菌培养、墨汁染色,到目前的隐球菌荚膜抗原(cryptococcal capsular antigen,CrAg)检测.CrAg检测操作简便快速,花费少,敏感性及特异性高,因此在世界范...     

Molecular typing and in vitro resistance of Cryptococcus neoformans clinical isolates obtained in Germany between 2011 and 2017

Cryptococcosis is a fungal infection of the central nervous system predominantly caused by Cryptococcus neoformans in immunocompromised patients. In several countries worldwide, up to 50% of isolates show in vitro resistance to clinically used antifungals including fluconazole. No prospective data on susceptibility to antifungal drugs are available for Germany. In this study, we characterised all C. neoformans isolates collected from individual patients’ samples at the German reference laboratory for cryptococcosis 2011 and 2017 (n = 133) by multi-locus sequence typing and phenotypic drug susceptibility testing. We identified serotype A/genotype VNI isolates belonging to clonal complexes previously described from Europe, Africa, Asia and South America as the most prevalent agents of cryptococcosis in Germany. Overall, we observed minimal inhibitory concentrations (MICs) above the epidemiological cut-offs (ECVs) in 1.6% of isolates regarding fluconazole and 2.3% of isolates regarding 5-flucytosine. Here, two C. neoformans var. grubii isolates displayed decreased drug susceptibility to fluconazole, one of them additionally to 5-flucytosine. We also found 5-flucytosine MICs above the ECV for two C. neoformans var. neoformans isolates. We identified a novel mutation in the ERG11 gene which might be associated with the elevated fluconazole MIC in one of the isolates. The clinical importance of the detected in vitro resistance is documented by patient histories showing relapsed infection or primary fatal disease. Of note, sertraline demonstrated antifungal activity comparable to previous reports. Systematic collection of susceptibility data in combination with molecular typing of C. neoformans is important to comprehensively assess the spread of isolates and to understand their drug resistance patterns.     

Chemotherapeutic activity of liposomal SJA-95: A new polyene macrolide antibiotic in experimental aspergillosis and cryptococcosis

The incidence of systemic fungal infections that has risen dramatically over the past three decades has propelled a continuous need for more potent antifungal drugs. The purpose of this research was to evaluate the chemotherapeutic activity of a new heptaene polyene macrolide antibiotic (SJA-95) and liposomal incorporated SJA-95 (lip. SJA-95) in a mouse model of aspergillosis and cryptococcosis respectively. Lip. SJA-95 was prepared in our laboratory by the proliposome method involving incorporation of the antifungal into the proliposome mixture and its subsequent conversion into a liposomal dispersion by a simple dilution step. Treatment with free SJA-95 and lip. SJA-95, both in aspergillosis and cryptococcosis, progressively prolonged the survival time and decreased the fungal loads in vital organs respectively. A higher LD₅₀ value of lip. SJA as compared to that of free SJA-95 was indicative of reduced toxicity of lip. SJA-95. Our findings suggest lip. SJA-95 treatment results in prolonged survival time, effective microbiological clearance and reduced toxicity that might help to establish its usefulness as a chemotherapeutic agent in systemic fungal infections with fewer adverse reactions.     

Longitudinal study of cryptococcosis in adult solid-organ transplant recipients

While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.     

肺隐球菌病1例报告并国内文献复习

目的：了解肺隐球菌病的发病特点，提高认识水平。方法：报告1例肺隐球菌病患者的临床资料，并通过检索中国医院数字图书馆系统，复习了60篇相关文献，总结其临床表现、影像学特点、诊断方法及治疗手段。结果：肺隐球菌病的临床表现无特异，影像学改变因患者的免疫功能不同而有差异，诊断依赖病理学，治疗尚存在争议。结论：肺隐球菌病的发病率逐年增高，应当受到重视，以提高诊断准确性。     

3例新型隐球菌脑膜炎的临床观察与护理

总结3例新型隐球菌脑膜炎的临床观察与护理,急性期早期加强颅内压的观察和护理,防止颅内压持续增高脑疝形成是治疗成功的关键。密切观察药物的毒副反应并及时处理,同时做好心理护理及基础护理。     

隐球菌脑膜炎的脑脊液细胞学（CSPC）观察分析

目的 观察隐球菌性脑膜炎的脑脊液细胞学表现及隐球菌镜下特征。方法 病人在入院后行腰穿检查，送检脑脊液常规墨汁涂片找隐球菌的同时，另外留取1-2ml标本行CSFC检查，用自然沉淀法收集脑脊液细胞于玻片上，经MGG染色后用光镜、油镜得出细胞反应类型及找隐球菌。结果 4例病人在常规墨汁涂片找到隐球菌；CSFC检查均检出隐球菌，其镜下特征为：深蓝、无核，大小与细胞相似，呈双层反光圈，多呈簇排列。其CSFC表现为混合细胞反应，且这种细胞反应持续时间长。结论 在常规墨汁涂片隐球菌的基础上，增加CSFC找隐球菌可提高隐球菌的阳性检出率及可靠性。