国产两性霉素B治疗侵袭性真菌感染121例临床分析

目的 观察静脉用国产两性霉素B对血液病患者侵袭性真菌感染(IFI)的临床疗效及其安全性.方法 选择121例血液病患者静脉使用两性霉素B,剂量为5～50 mg/d,用药时间5～101d,中位数为19 d,并对用药前后患者肝、肾功能及电解质进行监测.结果 静脉使用两性霉素B临床总有效率为67.3%,真菌清除率为66.7%.不良反应包括寒战、高热、低钾血症、肝肾功能损害、胃肠道反应、静脉炎和皮疹.结论 只要合理应用,对其不良反应进行积极防治,两性霉素B仍是较为安全有效的一线抗真菌药物.     

两性霉素B治疗血液病患者粒细胞缺乏合并真菌感染111例临床分析

目的 比较两性霉素B与其脂质体治疗血液病粒细胞缺乏并发侵袭性真菌感染(IFI)在临床疗效及安全性上的差异.方法 82例IFI患者使用两性霉素B,29例IFI患者使用两性霉素B脂质体.两性霉素B的中位累计剂量为617(60～1895)mg,治疗中位时间18(7～60)d.脂质体的中位累计剂量为925(140～3420)mg,治疗中位时间13(7～50)d.结果 两性霉素B组及其脂质体组的临床总有效率分别为69%、58%,两组比较差异无统计学意义(P＞0.05).两组不良反应比较,寒战、发热的发生率分别为21%、10%,低血钾症分别为34%、14%,肝脏损害分别为22%、17%,肾脏损害分别为9%、3%.以上不良反应中除低钾血症(P=0.03)外,其他不良反应比较差异均无统计学意义(P＞0.05).结论 两性霉素B与其脂质体总体疗效相近,两性霉素B组严重不良反应发生率稍高.只要合理使用,大多数不良反应可以控制.     

两性霉素B治疗恶性血液肿瘤合并真菌感染临床分析

目的观察静脉用两性霉素B对血液系统恶性肿瘤患者真菌感染的临床疗效及安全性。方法32例恶性血液病患者（男22例，女10例，中数年龄33．5岁），出现真菌感染者使用两性霉素B，剂量为5～50mg／d，用药天数为7～93d，中数25d。结果两性霉素B临床总有效率为53．1％，真菌清除率为53．8％，不良反应发生率中寒战、发热9．4％，低血钾12．5％，肝功能损害为15．0％，肾功能损害为18．8％。结论两性霉素B因其抗菌普较广，且疗效好，在治疗深部真菌感染中为高效药物，但因其不良反应较大，限制其使用。我们的研究表明，只要合理用药，定期监测肝肾功能，该药仍是一相对较为安全有效的药物。     

两性霉素B治疗49例血液恶性肿瘤患者深部真菌感染分析

目的观察两性霉素B对血液恶性肿瘤患者深部真菌感染的临床疗效及安全性。方法49例血液恶性肿瘤患者合并真菌感染使用两性霉素B,剂量为每日0．5～1 mg/kg,用药10～61 d,中位数26 d,观察用药前及用药后1周患者症状、体征,血电解质及肝、肾功能的变化。结果两性霉素B临床总有效率为56．9%,真菌清除率42．4%,各种不良反应发生率在3．6%～24．5%,常见的不良反应依次为两性霉素B输注的畏寒、寒战、发热等全身反应,低钾血症,消化道反应,肾功能损害,肝功能损害,静脉炎。结论两性霉素B抗菌谱广,抗菌作用强,虽不良反应较为多见,只要合理用药及不良反应处理得当,大多数患者仍可耐受。     

两性霉素B治疗侵袭性真菌感染152例临床分析

目的 观察国产静脉用两性霉素B去氧胆酸盐治疗侵袭性真菌感染(IFI)的疗效及安全性.方法 两性霉索B第1、2,3天剂量5、10、20 mg,第4天起每天25-40 mg,稀释后静脉滴注12 h以上,144例用药7-66 d,平均25 d,累积剂量平均670 mg,结果 两性霉素B治疗IFI临床有效率78.4%,不良反应发生率寒颤、发热39.1%,低血钾42.2%,消化道反应24.5%,肾功能受损9.5%.结论 国产两性霉素B抗真菌谱广,疗效好,每天剂量稀释后静脉滴注12 h以上,注意监测血钾水平和肝肾功能变化,是较安全的.     

卡泊芬净与米卡芬净治疗重症侵袭性真菌感染的临床疗效与药物利用评价

目的探讨卡泊芬净和米卡芬净治疗重症侵袭性真菌感染（invasive fungal infections,IFI）患者的临床疗效,评价药物利用。方法随机抽取四川省人民医院2009年1月至2011年12月分别经卡泊芬净和米卡芬净治疗的IFI病例各40例,分析评价卡泊芬净和米卡芬净治疗IFI的疗效、不良反应及药物利用情况。结果治疗总有效率卡泊芬净组为57.5%,米卡芬净组为55.0%,差异无统计学意义（P〉0.05）;两组首选治疗有效率均远高于三唑类（如氟康唑、伊曲康唑）、多烯类（如两性霉素B及其脂质体）治疗无效或不能耐受而进行的挽救治疗有效率,差异有统计学意义（P〈0.05）;不良反应发生率卡泊芬净组高于米卡芬净组,但差异无统计学意义（P〉0.05）;药物利用指数（DUI）卡泊芬净为0.985,米卡芬净为1.000,使用基本合理;日用药金额卡泊芬净为1942.04元/天,米卡芬净为1260.00元/天。结论卡泊芬净和米卡芬净治疗重症IFI的疗效相当,首选二者治疗的有效率均高于挽救治疗;二者不良反应发生率相近;DUI≤1.0,为合理用药。二者在疗效和不良反应相当的情况下,从经济学角度考虑米卡芬净更具优势。     

从两性霉素B治疗侵袭性肺曲霉病寻找临床切入点研究

目的：探讨从两性霉素B治疗侵袭性肺曲霉病寻找临床切入点的途径.方法：对慢性阻塞性肺疾病合并侵袭性肺曲霉菌病患者使用两性霉素B治疗过程中发生肾损害案例进行分析,提出适时药学监护.结果：及时根据肾功能指标调节药物剂量和处理两性霉素B相关不良反应,患者好转出院.结论：两性霉素B不良反应多,治疗过程中应加强药学监护,临床药师应从细节方面协助临床医师,保障安全、有效、合理用药.     

两性霉素B和伏立康唑治疗儿童急性淋巴细胞性白血病化疗期侵袭性真菌感染分析

目的:研究两性霉素B和伏立康唑治疗儿童急性淋巴细胞性白血病化疗期侵袭性真菌感染的临床效果。方法:回顾性分析2014年3月至2017年2月在我院确诊为急性淋巴细胞白血病并接受治疗的214例患者临床资料,有65例患儿在化疗期间发生侵袭性真菌感染(IFI),其中35例患儿接受伏立康唑治疗,为A组;30例患儿接受两性霉素B治疗,为B组。通过统计学分析影响IFI发生率的临床因素,并比较患儿用药8周后的治疗效果和不良反应的发生情况。结果:ALL患儿IFI发病率达到30.37%,患儿的IFI发生率与住院时间、中性粒细胞缺乏持续时间相关(P0.05)。A组与B组治疗的总有效率分别为72.28%和43.33%,2组相比差异具有统计学意义(P0.05)。伏立康唑治疗的患儿的肾功能损伤、消化功能障碍和神经毒性发生率分别为8.57%、5.71%和5.71%,明显低于两性霉素B治疗的患儿(P0.05)。A组患儿躯体健康和精力情况、情绪控制和总体健康评分指数明显高于B组患儿相应的评分指数,差异有统计学意义(P0.05)。结论:ALL患儿的IFI的发生率与患儿的住院时间、中性粒细胞水平相关,伏立康唑治疗的临床效果较好,且可降低不良反应发生率,有重要临床意义。     

去甲万古霉素在造血干细胞移植患者中应用的安全性和有效性研究

目的评价注射用去甲万古霉素在造血干细胞移植(HSCT)患者中应用的安全性和有效性,为临床用药提供依据。方法观察去甲万古霉素静脉用药的HSCT住院患者在用药期间发生的任何不良事件,判断不良事件与药物的关系、计算不良反应发生率,并观察疗效。结果2004年5月至2007年5月共入选病例95例,其中可进行临床和实验室安全性评价者93例。出现不良反应者共15例,不良反应发生率为16.1%。其中肾功能损害7例(7.5%)、肝功能损害4例(4.3%)、肝肾损害伴血尿者1例(1.1%)、肠道菌群失调1例(1.1%)、耳鸣1例(1.1%)、血栓性静脉炎1例(1.1%)。年龄≥45岁,合并应用其他易造成肾脏损伤药物(氨基糖苷类抗生素、两性霉素B、膦甲酸钠)都是造成肾脏损害的高危因素。而以上因素均不是肝脏损害的高危因素。可评价疗效的81例中,47例有效,总有效率58.0%。结论注射用去甲万古霉素在HSCT患者的临床应用中有一定的疗效,但不良反应发生率较一般人群高,合并应用其他易造成肾脏损伤药物(氨基糖苷类抗生素、两性霉素B、膦甲酸钠)易发生肾脏损害。     

两性霉素B雾化吸入加局部灌注联合伏立康唑治疗侵袭性肺部真菌感染研究

目的观察两性霉素B雾化吸入加局部灌注联合伏立康唑治疗侵袭性肺部真菌感染(IPFI)的临床效果。方法选取80例IPFI患者作为研究对象,采用简单随机分组法分为对照组和研究组,每组40例。对照组患者常规采用伏立康唑静脉滴注治疗,观察组患者在对照组基础上,采用两性霉素B雾化吸入联合纤维支气管镜局部灌注治疗。比较2组临床疗效、治疗时间和不良反应发生情况。结果研究组治疗时间为(14.82±3.36) d,显著短于对照组的(21.49±5.07) d(P 0.05);研究组临床总显效率为82.50%,显著高于对照组的60.00%(P 0.05);研究组不良反应总发生率为22.50%,低于对照组的32.50%,但差异无统计学意义(P 0.05)。结论两性霉素B雾化吸入加局部灌注联合伏立康唑是治疗IPFI的安全有效手段。     

不同时机两性霉素B脂质体治疗慢性阻塞性肺疾病合并侵袭性肺部真菌感染的疗效及安全性探讨

目的 探讨不同时机两性霉素B脂质体治疗慢性阻塞性肺疾病（COPD）合并侵袭性肺部真菌感染（IPFI）的疗效及安全性.方法 本文回顾性分析我科2010年8月至2012年2月,COPD合并IPFI的28例患者应用两性霉素B脂质体的临床资料,其诊断标准参见中华医学会呼吸分会制定的《慢性阻塞性肺病诊治规范2007修订版》和《侵袭性肺部真菌感染的诊断标准与治疗原则（草案）》,观察并探讨了不同时机两性霉素B脂质体治疗COPD合并IPFI有效性及治疗时机选择等,治疗期间监测肺影像学、肝肾功能电解质、体温等变化,以观察两性霉素B脂质体不良反应.结果 临床诊断、拟诊各22、6例;抢先/经验治疗组有效率为76.47％,高于挽救/目标治疗组的45.45％,差异有统计学意义（P＜0.05）;疗程比较方面：挽救治疗组疗程为（22.32 ±5.45）d,长于抢先治疗组的（13.40±4.34）d,差异有统计学意义（P＜0.05）;不良反应发生率比较：挽救治疗组不良反应率（57.14％）高于抢先治疗组不良反应率（39.29％）,且差异具有统计学意义（P＜0.05）.结论 两性霉素B脂质体是治疗COPD合并IPFI安全有效的药物,抢先治疗能提高疗效,且能减少不良反应发生率,临床工作中值得进一步研究证实.     

伊曲康唑治疗血液系统恶性肿瘤伴发真菌感染临床观察

目的观察伊曲康唑治疗血液系统恶性肿瘤患者伴发真菌感染的效果。方法选择我院2004年2月至2009年6月收治的恶性血液病合并侵袭性真菌感染患者(IFI)31例并分为两组,A组17例,予伊曲康唑注射液静脉注射2 d后改口服液续贯治疗,B组14例,予伊曲康唑注射液静脉注射14 d后改口服液续贯治疗。结果A组与B组IFI患者有效率分别为64.7%和64.3%。结论恶性血液病合并侵袭性真菌感染者应用改良伊曲康唑方案治疗有效,节约了医疗费用,其抗感染疗效与免疫力恢复速度密切相关。     

Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.     

Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B.

A study was performed to assess the in vivo relevance of the in vitro antagonism between fluconazole and amphotericin B against Candida albicans. Combinations of fluconazole and amphotericin B were explored for their efficacies against acute (100% mortality in 2 to 5 days) or less acute (100% mortality in 30 days) invasive candidiasis infections in mice with healthy immune systems and immunocompromised mice. Treatment efficacy was assessed by protection from mortality and/or a reduction in the fungal burden in tissue. In models of acute infection in mice with healthy immune systems or less acute infection in immunocompromised mice, combinations of fluconazole and amphotericin B were superior to fluconazole alone, and the effects were at least additive. Combination therapy was at least as efficacious as amphotericin B alone. In a different model of less acute infection in mice with healthy immune systems, combinations of fluconazole and amphotericin B showed no interactions and were no better than either drug alone. We conclude that combination therapy with fluconazole and amphotericin B is not antagonistic in vivo, in contrast to published in vitro studies, and, consequently, suggest that combination therapy should be considered in the management of clinical candidiasis.     

Invasive mold infections in cancer patients: 5 years' experience withAspergillus,Mucor, Fusarium andAcremonium infections

Twenty systemic mold infections due to hyphic fungi (molds) arising within the last 5 years in a 60-bed cancer department are analyzed. The most frequent risk factors were plants in ward (75%), prior therapy with broad spectrum antibiotics (70%), catheter insertion (70%), acute leukemia (65%) and neutropenia (60%). Before death, a definitive diagnosis was made in 40%, and a presumptive diagnosis in 60% of patients; post mortem the presumptive antemortem diagnosis was confirmed in all cases (100% of patients). Aspergillosis was the most common invasive fungal disease (55%), followed by mucormycosis (15%), fusariosis (15%), and acremoniosis (10%). Of 20 patients, 8 (40%) were cured or improved after antifungal therapy with amphotericin B, ambisome and/or itraconazole; 8/20 (40%) died of fungal infection and 4/20 (20%) of underlying disease with fungal infection. Even though the diagnosis was made and antifungal therapy started before death in 15/20 (75%), invasive mold infection had a 60% overall mortality in patients with malignant disease.     

The value of amphotericin B in the treatment of invasive fungal infections

Over the last 20 years, there has been an increase in the total number of invasive fungal infections (IFIs) and in infections caused by rare and emerging pathogens. This is due in part to the growing population of immunocompromised patients at risk of developing fungal infections. Three classes of antifungal agents are widely used for the treatment of systemic fungal infections: polyenes, azoles, and echinocandins. Polyenes were the first antifungal agents developed and have a long-standing history in the treatment of IFIs. The use of conventional amphotericin B has been limited because of toxic side effects, which have been reduced by the lipid formulations of amphotericin B. Treatment options for invasive mycoses have expanded with the recent introduction of the second-generation triazoles (voriconazole and posaconazole) and the echinocandins (caspofungin, micafungin, anidulafungin). Despite the increased number of antifungal drugs, resistance issues present a problem in the treatment of IFIs. Although some fungal pathogens display innate resistance, others have developed resistance secondary to selective pressure. This article briefly reviews the changing epidemiology of fungal infections and associated risk factors, resistance issues with commonly administered antifungal agents, and treatment options for IFIs, with a focus on polyenes.     

卡泊芬净治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染的临床观察

目的分析卡泊芬净治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染临床效果及安全性。方法选取2009年3月至2012年5月收治恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染患者50例,采用随机数字表法分为两性霉素B组和卡泊芬净组,分别采用两性霉素B和卡泊芬净静脉滴注治疗;比较两组患者临床治疗总有效率及不良反应发生率等。结果两性霉素B组总有效率(72.0%)与卡泊芬净组患者(76.0%)比较无显著差异(P>0.05);两性霉素B组不良反应发生率(36.0%)明显高于卡泊芬净组(P<0.05)。结论卡泊芬净早期治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染临床效果满意,且无严重不良反应。