Cladophialophora bantiana brain abscess in an immunocompetent patient

Cladophialophora bantiana is a dematiaceous mold with a predilection for causing central nervous system infection, particularly in normal hosts. A case involving a 79-year-old immunocompetent woman who presented with left-sided weakness and a ring-enhancing brain lesion is reported. She underwent surgical excision, which revealed a brain abscess due to C bantiana. The patient was treated with liposomal amphotericin B for several weeks, then switched to voriconazole and flucytosine, but eventually succumbed to the infection. Therapy is not standardized for this rare mycosis, and mortality remains high, even in immunocompetent patients. Additional studies to understand the pathogenesis of this infection and to improve outcomes are needed.     

茄病镰刀菌引起坏疽性脓皮病

患者男，５８岁，铁渣灼伤左上睑后，于眼睑部，左颞部及鼻中迅速出现红肿，化脓，坏死，结痂，溃烂，深达皮下及肌层。皮损区直接镜检及组织病理切片均发现大量真菌菌丝，８次真菌学培养为同一菌株ＣＺ９２１３生长。该菌株形态特征，生理测定及动物试验等真菌学研究鉴定证实为茄病镰刀菌。     

低剂量两性霉素B联合氟胞嘧啶治疗隐球菌脑膜炎的临床分析

目的 探讨采用低剂量两性霉素B联合氟胞嘧啶治疗非获得性免疫缺陷综合征(AIDS)相关隐球菌脑膜炎(隐脑)的临床疗效及安全性.方法 回顾性分析复旦大学附属华山医院1998年1月至2007年12月间,低剂量两性霉素B(<0.7 mg·kg~(-1)·d~(-1))联合氟胞嘧啶治疗非AIDS相关隐脑1周以上、资料完整的31例病例,总结其临床特征,分析其临床疗效、药物不良反应及预后转归.结果 31例患者中,8例患者合并基础疾病,确诊时最常见的临床表现为头痛、发热、脑膜刺激征、呕吐,22例(78.6%)患者的颅脑MRI或CT检查发现异常.应用低剂量两性霉素B联合氟胞嘧啶治疗后,完全应答率19.4%(6/31),部分应答率54.8%(17/31),总有效率74.2%.除1例失访外,其余患者随访1年的归因病死率及全因病死率分别为0(0/30)和10.0%(3/30).此外,26例(83.9%)患者出现两性霉素B相关不良反应,以肝肾功能损害、心律失常、贫血为多见,但大部分不良反应均可耐受.结论 低剂量两性霉素B联合氟胞嘧啶治疗非AIDS相关隐脑,有较好的疗效和安全性.     

紫外分光光度法测定氟胞嘧啶片的溶出度

目的 建立测定氟胞嘧啶片溶出度的紫外分光光度法.方法 通过对不同方法、转速、溶出介质的选择,确定氟胞嘧啶片的溶出度方法.结果 采用2010年版<中国药典(二部)>附录XC第二法,以水1 000mL为溶出介质,转速为50 r/min,温度为(37±0.5)℃,采用紫外分光光度法,测定波长276 nm.结论 该方法简便快捷,可作为氟胞嘧啶片的溶出度测定方法.     

人外周血内皮祖细胞转染自杀基因杀伤恶性胶质瘤细胞的体外研究

目的观察5-氟胞嘧啶诱导基因修饰型内皮祖细胞群发生自身死亡及其旁效应对共培养人脑胶质瘤细胞系U251的杀伤作用。方法采用密度梯度离心法分离经体外诱导培养的人外周血内皮祖细胞,经转染获得基因修饰型内皮祖细胞。RT-PCR法鉴定胞嘧啶脱氨酶(CD)基因在基因修饰型内皮祖细胞中的表达变化,观察野生型和基因修饰型内皮祖细胞在不同浓度5-氟胞嘧啶作用下的细胞存活率,以及基因修饰型内皮祖细胞所诱导的旁效应。结果真核细胞表达载体pCEA-CD-CAUP转染成功,CD基因在基因修饰型内皮祖细胞中表达阳性;在不同浓度5-氟胞嘧啶(0.01～1000.00μg/ml)作用下,基因修饰型内皮祖细胞存活率低于野生型内皮祖细胞,组间差异有统计学意义(均P<0.05)。不同比例的基因修饰型内皮祖细胞与人脑胶质瘤细胞系U251共培养72h后,其细胞生长抑制率均高于基因修饰型内皮祖细胞所占的比例,当基因修饰型内皮祖细胞比例占细胞总数的50%时,细胞生长抑制率即已>80%。结论人外周血内皮祖细胞转染CD基因后,在5-氟胞嘧啶的作用下可发生自身死亡并触发旁效应而杀伤共培养的人脑胶质瘤细胞系U251细胞,为抗血管生成药物与自杀基因联合应用治疗恶性胶质瘤的体内实验及后续研究提供了依据。     

Méningite à Candida albicans chez l’adulte,apport des nouveaux moyens diagnostiques

Candida albicans or non-albicans are a frequent source of infection but seldom displayed in cerebrospinal fluid although responsible of an important number of nosocomial meningitis. Diagnosis is difficult which often delays treatment, which in turn hinders prognostic. This clinical case shows a patient afflicted with a deadly C. albicans meningitis and allows us to focus on new diagnostic tools and advice against this infection.     

造血系统恶性疾病并发真菌败血症临床分析

目的 探讨造血系统恶性疾病并发真菌败血症的防治措施。方法 回顾性分析近6年来18例造血系统恶性疾病并发真菌败血症患者的临床情况。结果 真菌败血症占血液系统医院感染的3．7％，热带念珠菌是主要菌种，占72．2％，病死率达38．9％，真菌败血症的发生与原发病、强烈化疗、大剂量免疫抑制剂及抗生素长期反复应用有关；氟康唑、两性霉素B 5—氟胞嘧啶治疗有效率分别为14．3％、63．6％。结论 非白色念珠菌败血症有增多之势，尽早明确诊断、及时防治是关键，治疗首选两性霉素B 5—氟胞嘧啶。     

An accelerated stability study of 5‐flucytosine in intravenous solution

The stability of the antimycotic drug flucytosine (5FC) and the extent of 5fluorouracil (5FU) formation in 5FC intravenous solution was studied in an accelerated stability experiment. 5FC intravenous solution (10 mg/ml) was heated at 40, 60, 70, 80 and 90 C for a maximum of 131 days. At appropriate time intervals samples were taken and the concentrations of 5FC and 5FU were determined using a newly developed, stability indicating HPLCUV method. Heating the 5FC intravenous solution at 40, 60, 70, 80 and 90 C lead to 5FC decomposition of respectively 0, 8.9, 14.4, 52.5 and 61.6%. The Arrhenius plot of the 5FC decomposition is described by: Lnk5-FC decomposition = 80.1892 * 1/T 0.2396 and the 5FU formation is described by Lnk5FU formation = 13087 * 1/T + 34.4028. It is concluded that 5FC is very stable in intravenous solution at regular storing temperatures and can therefore be stored at ambient temperatures for several years before the critical limit of 95% 5FC is reached. However, the toxic and teratogen degradation product 5FU may be present in considerable amounts in the product, due to both impurities in the raw material and the formation from 5FC upon sterilisation and storage.     

Studies on the Antifungal Effect of Flucytosine (Ancobon®, Ancotil®)

Summary: The antifungal activity of Flucytosine (Ancobon®, Ancotil®) was tested against different pathogenic fungi. Five strains of each fungus species were used. Two different techniques were applied, namely the plate serial dilution and the time-concentration exposure procedure. Fungi of the yeast, yeast-like organisms, the tissue form of Blastomyces dermatitidis, and Sporotrichum schenckii were inhibited (fungistatic and/or fungicidal effect) at a concentration varying from 10–10,000μg/ ml medium. A concentration of 10 μg/ml medium proved to be fungicidal for Aspergillus fumi-gatus and Penicillium rubrum strains, however, a strain of both A. fumigatus A. candidum required a somewhat higher concentration of 20 μg/ml medium. The tested dermatophytes and nocardiae were not affected at all at the highest used concentration of the drug (2000–10,000 μg/ml medium). The growth of the facultative pathogenic fungi was totally inhibited at a concentration of 1000–2000 μg/ml medium. Using the time exposure procedure, the substance inhibited the growth of the tested yeast and yeast-like fungi at a concentration varied from 10–10,000 μg/ml in a time ranging from 1–6 hours. In this respect, C. rugosa, B. dermatitidis, Trichosp. cutane-um and G. candidum needed the highest used concentration (10,000 μg/ml) and the maximum exposure time (6 hrs.). A relatively longer exposure time up to 24 hrs. was required for the drug to inhibit the growth of the facultative pathogenic fungi. The substance did not exert any noticeable effect against the tested dermatophytes and nocardiae strains. The results are seen as encouraging and promising for the possible use of Flucytosine as a chemotherapeutic agent in veterinary medicine, especially in combating mammalian and avian respiratory tract infections caused by A.^: fumigatus and other allied fungi and also in cases of udder mycotic infections of both bovine and swine, particularly when C. tropicalis, C. guilliermondii and Torulopsis species are encountered. Zusammenfassung: Die antimykotische Wirksamkeit von Flucytosin (Ancotil®, Ancobon®) gegen verschiedene pathogene Pilze wurde untersucht. Fünf Stämme von jeder Pilz-Art wurden getestet. Zwei verschiedene Verfahren wurden angewendet, nämlich die Platten-Verdünnung und die Zeit-Konzentration-Expositionsmethode. Hefen, hefeähnliche Pilze, die Gewebe-Form von Blastomyces dermatitidis und Sporotrichum schenckii wurden bei unterschiedlichen Konzentrationen von 10–10 000 μg/ ml Nährboden) gehemmt. Eine Konzentration von 10 μg/ml Nährboden hatte eine pilzäbtotende Wirkung für Aspergillus fumigatus- und Penicillium rubrum-Stämme, jedoch brauchte je ein Stamm von beiden Arten (A. fumigatus und A. candidum) eine etwas höhere Konzentration von 20 μg/ml Nährboden, um das Gleiche zu erzielen. Die getesteten Dermatophyten und Nocardiae waren bei der hoheren angewendeten Konzentration der Substanz (2000–10 000μg/ml Nährboden) nicht beeinflußt. Das Wachstum der fakultativ pathogenen Pilze war generell bei einer Konzentration von 1000–2000 μg/ml Nährboden gehemmt. Unter den Bedingungen der Zeit-Konzentration-Expositionsmethode wurde das Wachstum der getesteten Hefen und hefeähnlichen Pilze bei einer Konzentration von 10–10 000 μg/ml in einem Zeitraum von 1–6 Stunden gehemmt. In dieser Beziehung bedurften C. rugosa, B. dermatitidis, Trichosp. cutaneum und G. candidum der höchsten angewendeten Konzentrationen (10 000 μg/ml) und Expositionszeiten (6 Stunden). Die Substanz hatte auf die getesteten Dermatophyten und Nocardiae keine be-merkbare Wirkung. Die Ergebnisse sind als ermutigend und vielversprechend für die mögliche Anwen-dung von Flucytosine als chemotherapeutisches Mittel in der Veterinär-Medizin, insbesondere für die Bekämpfung von Säugetier- und Geflügel-Atemwegsinfektionen, die durch A. fumigatus und ähnliche Pilze verursacht werden, anzusehen. Das gleiche gilt für mykotische Euterinfektionen von Rind und Schwein, wenn diese von C. tropicalis, C. guilliermondii oder Torulopsis-Arten hervorgerufen werden.