Oral, Topical and Parenteral Antifungal Treatment with Itraconazole in Normal and in Immunocompromised Animals

Summary: Itraconazole was dissolved in polyethylene glycol for oral and topical treatment and in hydroxypropyl-β-cyclo-dextrin for oral, topical or parenteral treatment.
Topical and oral treatment was successful in microsporosis, trichophytosis, skin-and vaginal candidosis, pityrosporosis and eye mycosis by Candida, Fusarium and Aspergillus . Vaginal candidosis could be cured with a one-day topical or oral treatment.
The same results could not be obtained with any of the reference compounds (griseofulvin, terbinafine, ketoconazole or fluconazole) on amg per kg body weight base, nor on a% concentration base. Antifungal levels were determined by bioassay: biologically active antifungal levels were present in plasma and vaginal fluid of rats, after one oral dose of 10mg.kg^-1, for at least 72 and 96 hours respectively. This was in good correlation with findings on prophylaxis of vaginal candidosis. Itraconazole was also successfully used, in normal animals and animals immunodepressed with various agents, in disseminated and systemic diseases: trichophytosis, sporotrichosis, histoplasmosis, candidosis, aspergillosis and cryptococcosis. Oral and parenteral treatment with itraconazole was compared in various models to oral and parenteral fluconazole and to parenteral amphotericin B. The outcome with itraconazole was better than with the other antifungals. Meningeal cryptococcosis responded very well to itraconazole. Combination therapy of itraconazole and fluconazole was not superior to treatment with itraconazole alone. No side-effects were observed in relation to itraconazole treatment.b     

肺隐球菌病的影像学表现(附32例分析)

目的：总结肺隐球菌病的影像学表现。方法：肺隐球菌病32例，分别误诊为肺癌、炎症或结核。患者年龄4～64岁；X线检查30例，CT检查19例。结果：肺隐球菌病X线、CT表现有5种：①孤立块影或结节影；②多发结节或肿块影；③单发或多发斑片影；④斑片影与结节影混合病灶；⑤弥漫性粟粒影；这5种表现以第1种最多见，好发于肺外围。32例病例手术病理证实20例，穿刺活检证实5例，脑脊液涂片证实4例，痰培养证实3例。结论：肺隐球菌病的影像表现缺乏特异性，诊断依赖病理学检查及痰、脑脊液找到隐球菌证实，当肺部阴影诊断不明时在鉴别诊断上应考虑此病。     

Cryptococcus neoformans infection in malignancy

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV‐infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over‐represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.     

Molecular epidemiology reveals genetic diversity among 363 isolates of the Cryptococcus neoformans and Cryptococcus gattii species complex in 61 Ivorian HIV‐positive patients

Cryptococcal meningitis is a severe opportunistic infection in HIV‐infected patients. In Ivory Coast, despite the availability of antiretroviral treatment (ART), this infection is still prevalent. The study investigates the genetic diversity of 363 clinical isolates of Cryptococcus from 61 Ivorian HIV‐positive patients, the occurrence of mixed infections and the in vitro antifungal susceptibility of the isolates. Serotyping was performed via LAC1 and CAP64 gene amplification. Genotyping was performed using the phage M13 core (GACA)₄ and (GTG)₅ primers and restriction fragment length polymorphism analysis of the URA5 gene. By PCR fingerprinting, the presence of the three serotypes were demonstrated among the 363 isolates in the population studied: A (n=318; 87.6%), AD (n=40; 11%) and B (n=4; 1.1%). Using PCR fingerprinting with primers M13 (GACA)₄ and (GTG)₅, we grouped the isolates into 56 molecular subtypes. We observed a high frequency (39.3%) of mixed infections, with up to two different genotypes per sample. None of the isolates were resistant to amphotericin B. Only 0.3% and 1.1% of the isolates were resistant to fluconazole and flucytosine respectively. This study revealed the high genetic diversity among Cryptococcus isolates, the occurrence of mixed infections and a high antifungal susceptibility for the majority of Ivorian cryptococcal isolates.     

结节型与团块渗出型肺隐球菌病的临床特征分析

目的：将肺隐球菌病（pulmonary cryptococcosis，PC）患者肺部CT表现分为结节为主型或团块渗出为主型两组，分析两组患者的临床表现的差异，为早期诊断识别肺隐球菌病提供帮助。方法：回顾性分析2010年1月1日至2021年1月1日期间复旦大学附属中山医院非HIV感染PC的住院患者，依据首次诊断时胸部CT病灶表现，分为结节型组、团块渗出型组，收集并分析两组间年龄、性别、基础疾病、临床症状、炎症指标和隐球菌荚膜抗原(CrAg)等相关临床资料。结果：本研究共纳入患者187例（男女比例1.71：1），分为结节型组（121例，64.7%）、团块渗出型组（66例，35.3%）。与结节型组患者比较，团块渗出型组发病年龄更早[（46.61±15.35）岁 vs （53.31±12.39）岁，P<0.01]；咳嗽（57.6% vs 35.5%，P<0.01）、咳痰（36.4% vs 17.4%，P<0.01）、发热（36.4% vs 11.6%，P<0.01）更多见；血沉[（28.34±24.11）mm/H vs（16.08±16.41）mm/H，P<0.01]、C反应蛋白[（18.20±25.02）mg/L vs （6.35±12.71）mg/L，P<0.01]更高；淋巴细胞比例低于20%的发生率更高（46.9%vs 25.4%，P<0.01）；CrAg阳性率更高（93.4% vs 81.3%，P<0.05），CrAg滴度更高（采用-lg值表示，2.01±0.93 vs 1.08±0.81，P<0.05）。而两组间白细胞计数、中性粒细胞计数、中性粒细胞比例、淋巴细胞计数、降钙素原均无显著性差异（P>0.05）。结论：非HIV感染PC患者胸部CT结节型更多见（64.7%）。相较于结节型患者，团块渗出型PC患者年龄更小、临床症状更多、炎症指标更高、CrAg阳性率及滴度更高。     

基于CT平扫影像组学模型鉴别结节/肿块型 肺隐球菌病及肺腺癌与肺结核

目的 探讨基于CT平扫影像组学预测模型鉴别诊断结节/肿块型肺隐球菌（PC）与肺腺癌、肺结核（TB）的可行性。方法 回顾性分析28例结节/肿块型PC和30例肺腺癌、26例TB的平扫CT资料，提取病灶纹理特征，对其进行特征选择，获得PC组与肺腺癌组、PC组与肺TB组之间存在显著差异的特征参数。按7：3比例将所有样本分为训练集合测试集，采用随机森林法以较优特征参数建立预测模型，对训练集数据进行评估，之后于测试集数据进行验证；绘制相应ROC曲线，评估模型的鉴别诊断效能。结果 针对PC和肺腺癌、PC和肺TB分别获得7个和4个较优纹理特征参数。测试集验证结果显示模型鉴别PC与肺腺癌以及PC与肺TB的AUC、敏感度、特异度、准确率分别为0.96、1.00、0.78、0.89及0.99、0.88、0.89、0.88。结论 基于CT平扫图像影像组学可用于鉴别诊断结节/肿块型PC及肺腺癌与肺TB。     

Uncommon yeast infections in hematological patients: from diagnosis to treatment

Invasive fungal diseases have been recognized with increasing frequency as major pathogens in patients with cancer over the past few decades, as a result of new and more aggressive anticancer treatments and supportive care, and this has been especially reported for patients suffering from hematological malignancies. In these settings, typically uncommon yeasts and filamentous fungi have recently emerged as significant human pathogens, frequently as breakthrough infections in patients receiving empirical antifungal therapy or antifungal prophylaxis and with reported high crude mortality rates. The aim of this article is to discuss certain aspects of the approach to invasive fungal diseases due to uncommon yeasts (e.g., Trichosporon spp., Blastomyces spp. and Cryptococcus spp.) in patients with hematological malignancies, focusing on epidemiology, diagnosis, treatment outcomes and the role of novel antifungal drugs (i.e., new triazoles and echinocandins).     

兔肺隐球菌病的CT表现

目的建立标准化不同免疫状态新西兰大白兔肺隐球菌病模型,探讨肺隐球菌病急性期CT表现,并与病理进行对照。方法健康新西兰大白兔40只,随机分为免疫抑制组及免疫正常组。对免疫抑制组注射阿糖胞苷以诱导免疫抑制状态,对全部动物均注射抗生素以预防细菌感染;通过气道注射的方式接种隐球菌菌株,接种后隔天行CT扫描并与病理对照。结果两组病变类型均以实变为主,且多发生于胸膜下,免疫抑制组急性期易出现结节。免疫抑制组病灶多为多发且病程演变过程中病灶范围多有扩大。结论不同免疫状态兔肺隐球菌病急性期病变均以斑片浸润为主,但部分模型肺部亦出现结节、团块改变,提示在急性肺隐球菌病早期即可出现结节、团块样病变。