Prophylaxis of Fungal Infections with Itraconazole during Remission-Induction Therapy

Summary: Deep fungal infections are an increasing problem in the treatment of acute leukemias and malignant lympho-mas. Risk factors are known but unavoidable. Because of diagnostic difficulties most patients are treated empirically with intravenous amphotericin B. This drug's toxicity increases morbidity and mortality. An orally absorbable triazole derivative, itraconazole, may offer effective and safe prophylaxis against deep candidosis and aspergillosis in these patients.
Such infections have been treated successfully with oral itraconazole even when resistant to intravenous amphotericin B. In retrospective comparative studies there are significantly less deep fungal infections in patients given itraconazole. The significance of the difference varies between studies. Pharmaco-kinetic data confirm therapeutic plasma levels of itraconazole but with wide variation within and between patients.
The current large, multi-centre, randomised, double-blind, prospective trial of oral itraconazole versus placebo in the U.K. will test its prophylactic efficacy against deep fungal infections during treatment of haematological malignancies.     

颅内曲霉菌脓肿15例临床特征研究

目的　探讨颅内曲霉菌脓肿的发病机制与临床特点 ,选择有效治疗方法。方法　回顾性分析 15例颅内曲霉菌脓肿 ,探讨颅内曲霉菌脓肿的发病机理、临床症状、影像学特点、诊断与鉴别诊断、治疗方法。结果　本组发现感染来源为 :鼻源性 7例 ,耳源性 2例 ,肺源性 5例 ,脑外伤 1例。临床症状有头痛、发热 ,有时合并鼻窦炎、中耳乳突炎与颅底神经损害症状。 5例肺源性均有肺部曲霉菌病 ,4例有脑叶内环状强化病变。 7例鼻窦与 2例耳源性有鼻旁窦与乳突软组织团块影、颅底骨质破坏与硬膜外和 /或脑叶内环状强化病变 ,5例有颅底神经损害。治疗方法为联合应用开颅手术与各种抗真菌药物 ,死亡 5例 ,无复发。结论　曲霉菌可以通过多种途径感染中枢神经系统 (CNS) ,鼻窦炎与中耳乳突、肺部是常见的感染来源。本病好发于经常接触发霉稻草的农民与长期大量使用糖皮质激素与抗生素的患者。肺源性临床特点与细菌性脓肿相似 ,但鼻窦与耳源性有特殊表现。术前诊断困难 ,应尽早开颅手术加早期、长程、口服伊曲康唑治疗     

Enhancing the in vitro and in vivo activity of itraconazole against breast cancer using miltefosine-modified lipid nanocapsules

Itraconazole (ITC), a well-tolerated antifungal drug, exerts multiple anticancer effects which justified its preclinical and clinical investigation as potential anti-cancer agent with reduced side effects. Enhancement of ITC anti-cancer efficacy would bring valuable benefits to patients. We propose herein lipid nanocapsules (LNCs) modified with a subtherapeutic dose of miltefosine (MFS) as a membrane bioactive amphiphilic additive (M-ITC-LNC) for the development of an ITC nanoformulation with enhanced anticancer activity compared with ITC solution (ITC-sol) and unmodified ITC-LNC. Both LNC formulations showed a relatively small size (43–46 nm) and high entrapment efficiency (>97%), though ITC release was more sustained by M-ITC-LNC. Cytotoxicity studies revealed significantly greater anticancer activity and selectivity of M-ITC-LNC for MCF-7 breast cancer cells compared with ITC-sol and ITC-LNC. This trend was substantiated by in vivo findings following a 14 day-treatment of murine mammary pad Ehrlich tumors. M-ITC-LNC showed the greatest enhancement of the ITC-induced tumor growth inhibition, proliferation, and necrosis. At the molecular level, the tumor content of Gli 1, caspase-3, and vascular endothelial growth factor verified superiority of M-ITC-LNC in enhancing the ITC antiangiogenic, apoptotic, and Hedgehog pathway inhibitory effects. Finally, histopathological and biochemical analysis indicated greater reduction of ITC systemic toxicity by M-ITC-LNC. Superior performance of M-ITC-LNC was attributed to the effect of MFS on the structural and release properties of LNC coupled with its distinct bioactivities. In conclusion, MFS-modified LNC provides a simple nanoplatform integrating the potentials of LNC and MFS for enhancing the chemotherapeutic efficacy of ITC and possibly other oncology drugs.     

那他霉素联合伊曲康唑治疗真菌性角膜炎的疗效分析

目的观察那他霉素滴眼液联合伊曲康唑胶囊治疗真菌性角膜炎的临床疗效。方法选取2014 年3月-2016年5月浙江省宁波市眼科医院收治的真菌性角膜炎患者92 例,随机分为观察组（那他霉素滴眼液+伊曲康唑胶囊）和对照组（那他霉素滴眼液）,两组患者治疗14 d 后对比临床疗效、治疗前后角膜染色、共聚焦角膜显微镜等,并记录与治疗相关不良反应发生情况。结果观察组临床治疗总有效率为86.96%、对照组为63.04%,观察组高于对照组（p <0.05）。观察组治疗后角膜染色阳性率为13.04%、对照组为36.96%,观察组低于 对照组（p <0.05）。结论对于真菌性角膜炎患者在局部使用那他霉素滴眼液基础上,配合口服伊曲唑康胶囊能够提高临床疗效,用药方便,值得临床推广应用。     

伊曲康唑对灰指甲的治疗效果临床观察

目的：观察在临床治疗灰指甲中伊曲康唑的治疗效果。方法：选取2012年6月-2013年6月在我院接受治疗的灰指甲病患24例，按照伊曲康唑服用剂量的不同，将其分成治疗组与对照组，每组12例，为照组中的病患每天提供lOOmg的伊曲康唑，为治疗组申的病患每周提供200mg的伊曲康唑，对比两组病患的治疗效果。结果：经过1到3个月的治疗后，对比两组病患的治疗效果，总治愈率均为100％，镜检真菌结果为阴性，治疗效果相同，P〉O．05，缺少统计学差异意义。对比两组病患的副反应发生率，治疗组副反应发生率为O％，明显低于对照组16．7％的副反应发生率，P〈O．05，具有统计学差异意义。结论：在临床治疗灰指甲病患时，小剂量使用伊曲康唑不仅治疗效果好，而且毒副作用小，经济负担轻，可以加强推广使用。     

Itraconazole is not effective for the prophylaxis of fungal infections in patients with neutropenia

 Fungal infections are a major problem among patients with hematological malignancies. To evaluate the efficacy of itraconazole (200 mg twice daily) in the prophylaxis of fungal infections in neutropenic patients, we conducted a prospective trial. A total of 61 patients with acute leukemia (113 cytotoxic chemotherapy episodes) were enrolled in the study. One patient in the itraconazole group was excluded because itraconazole was not taken due to gastrointestinal hemorrhage. Because the duration of neutropenia (neutrophil count, <0.5 × 10⁹/l) did not reach 7 days, 3 (1 patient) and 13 (4 patients) cytotoxic chemotherapy episodes in the itraconazole and control groups, respectively, were excluded. After these exclusions, the study population consisted of 31 patients (54 cytotoxic chemotherapy episodes) who had taken itraconazole and 24 patients (43 cytotoxic chemotherapy episodes) who had not taken itraconazole. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (absolute neutrophil count, >1 × 10⁹/l) unless a systemic fungal infection was documented or suspected. Thirteen episodes (24%) in the itraconazole group and 7 episodes (16%) in the control group proceeded to intravenous amphotericin B (P > 0.05). Fungal infections occurred in 9 episodes (17%) in the itraconazole group and in 5 episodes (12%) in the control group (P > 0.05). Overall mortality was five deaths in the itraconazole group and two in the control group. These deaths were not due to clinically documented fungal infection. In our study, efficacy of itraconazole in the prophylaxis of fungal infections in neutropenic patients was not detected. Received: March 25, 2002 / Accepted: October 1, 2002     

伊曲康唑注射液治疗真菌感染17例临床分析

目的评价伊曲康唑注射液治疗侵袭性肺部真菌感染(IPFI)的疗效。方法收集广东省人民医院呼吸科2006年使用伊曲康唑注射液治疗侵袭性肺部真菌感染患者17例,对其疗效进行分析研究。PFI诊断根据“IPFI的诊断标准与治疗原则(草案)”,确诊病例9例,临床诊断5例,拟诊病例3例。结果17例患者中共培养出真菌14株,包括白色念珠菌5株,曲霉菌6株,未分类真菌3株。在接受治疗的17例患者中,痊愈9例,显效2例,进步3例,无效(死亡)3例,总有效率为64.7%。12例接受氟康唑针剂治疗后改为伊曲康唑者9例有效,3例死亡。死亡的3例中2例为肾移植术后感染,1例为糖尿病酮症酸中毒的患者。在治疗过程中仅3例患者有轻微恶心、呕吐,未观察到严重的副反应。结论伊曲康唑注射液是治疗侵袭性肺部真菌感染有效的药物,临床上可作为一线用药治疗使用。