伊曲康唑针剂治疗深部真菌感染27例分析

对我科2004-11～2005-12采用伊曲康唑针剂治疗深部真菌感染27例分析如下。 1临床资料 1.1 一般资料 本组男21例，女6例，年龄25～82岁。1.2 方法 本组均采用伊曲康唑针剂静脉滴注。治疗第1、2天2次／d，每次1h静滴200mg伊曲康唑；从第3天开始，1次／d，每次1h静滴200mg。疗程15～20d。     

伊曲康唑治疗重症血液病患者真菌感染的临床观察

目的 探讨伊曲康唑对于重症血液病患者深部真菌感染的疗效.方法 12例重症血液病患者(急性再生障碍性贫血2例,急性非淋巴细胞白血病6例,急性淋巴细胞白血病4例),应用伊曲康唑静脉治疗深部真菌感染,部分患者有效后改为口服伊曲康唑混悬液序贯治疗.结果 12例患者中10例有效(有效率83.3%),1例因肾毒性停止治疗,1例为光滑念珠菌感染,根据药敏改为两性霉素B治疗后好转.结论 伊曲康唑治疗谱广,疗效肯定,不良反应少,可以作为重症血液病患者深部真菌感染的一线经验性用药,但需要注意其相关毒副作用,改善患者整体状况,以取得更佳疗效.     

卡泊芬净联合伊曲康唑治疗侵袭性肺部真菌感染的效果分析

目的评价醋酸卡泊芬净联合伊曲康唑治疗侵袭性肺部真菌感染的疗效与安全性。方法侵袭性肺部真菌感染患者35例,应用计算机随机分为两组,治疗组18例,给予醋酸卡泊芬净静脉滴注,首日70mg,次日起50mg／d,患者临床症状基本消失且体温正常5d、或连续痰标本涂片阴性后3d改为口服伊曲康唑胶囊200mg／d;对照组17例,静脉滴注伊曲康唑注射液,第1、2天每日2次,每次200mg,以后每日1次,每次200mg,连续12d;14d后改为口服伊曲康唑胶囊200mg／d。两组均以患者的临床症状、影像学和痰及肺泡灌洗液真菌连续培养均正常1周以上等作为停药指标。观察两组患者的疗效与不良反应发生情况。结果治疗组治愈8例,显效6例,总有效率为77．78％（14／18）;对照组治愈5例,显效6例,总有效率为64．30％（11／17）,两组总有效率差异有统计学意义（X^2=27．41,P=0．03）;治疗组与对照组不良反应各有2例,差异无统计学意义（P〉0．05）。结论两种方案对侵袭性肺部真菌感染均有效,卡泊芬净静脉滴注后2—4周口服伊曲康唑有较好的疗效,且安全性好。     

伊曲康唑治疗老年AECOPD肺部真菌感染疗效观察

目的 观察伊曲康唑治疗老年慢性阻塞性肺疾病急性加重(AECOPD)继发肺部真菌感染疗效及安全性.方法 将48例老年AECOPD患者随机分为2组,A组静脉注射伊曲康唑注射液,第1、2天200 mg,2次/d;第3～14天200 mg,1次/d;第.15天起服伊曲康唑口服液200 mg,2次/d;序贯治疗28 d.B组静脉注射氟康唑注射液,第1、2天200 mg,2次/d;第3～14天200 mg,1次/d;第15天起服氟康唑胶囊200mg,2次/d;序贯治疗28 d.2组分别于用药后7、14、28 d留取痰液行真菌培养,并观察不良反应.结果 A组临床真菌清除率为58.33％,B组临床真菌清除率为20.83％,两组药品不良反应发生率分别为12.5％和25.0％.结论 伊曲康唑治疗老年AECOPD继发肺部真菌感染疗效优于氟康唑,但心功能不全患者应慎用,使用过程中需严密监测药物的不良反应.     

伊曲康唑治疗造血干细胞移植患者真菌感染的临床观察

目的观察造血干细胞移植(HSCT)患者出现真菌感染的临床特点,并探讨伊曲康唑抗真菌感染的疗效。方法对该院2008年1月至2010年10月334例接受HSCT术治疗的病例真菌感染的临床治疗情况进行回顾性分析。90例HSCT患者术后被诊断为真菌感染,全部病例均予静脉注射伊曲康唑治疗,125~250毫克/次,第1、2天给予2次/天,第3天后给予1次/天,病情稳定后改为伊曲康唑口服液治疗。结果 HSCT患者术后真菌感染的发生率为27%,接受伊曲康唑治疗的患者有效率75.6%。确诊患者中10例(76.9%)有效,临床诊断病例58例(75.3%)有效。结论 HSCT患者术后真菌感染发病率高;伊曲康唑疗效明确,可用于HSCT患者术后患者抗真菌感染的治疗。     

静脉输注伊曲康唑注射液的体会

伊曲康唑(Itracnazole,商品名Sporanox,斯皮仁诺)是一种第2代三唑类合成的广谱抗真菌药,在治疗各种真菌感染时有较好的疗效[1]。1临床资料病人,男,52岁,乙型肝炎并肝硬化(失代偿期),合并真菌性肺炎(曲霉菌)。静脉输注伊曲康唑注射液每天1次,每次200mg,时间为30d。后改为口服伊曲康唑胶囊200mg,每日2次。2护理因伊曲康唑易与其他药液发生反应,在使用此药过程中,若仅输注此种液体时,按伊曲康唑注射液说明书配制,每支250mg,用普通输液器连接此液体自带的延长管直接输注,注意用此药自带的稀释液稀释,用外包装袋避光输注,滴速1mL/min,输入200mg…     

伊曲康唑治疗深部真菌感染疗效观察

目的：探讨伊曲康唑治疗深部真菌感染的临床疗效。方法：23例深部真菌感染患者采用伊曲康唑针剂静脉滴注（症状好转后改为口服）治疗，疗程15-20d。结果：可评价病例22例中17例有效，其中治愈12例（54．5％），显效5例（22．7％），无效5例（22．7％），有效率为77．3％。结论：伊曲康唑治疗深部真菌感染疗效较好，不良反应轻，患者耐受好，可作为临床治疗深部真菌感染的首选。     

蟹黄肤宁软膏联合伊曲康唑治疗花斑癣疗效观察

目的观察蟹黄肤宁软膏联合伊曲康唑胶囊治疗花斑癣的疗效。方法将60例确诊的花斑癣病例,随机分为治疗组和对照组各30例。所有患者皮损处均外用蟹黄肤宁软膏(螃蟹壳、黄柏、苦参、昆布、哈壳),2次/d。治疗组加用口服伊曲康唑胶囊200 mg,2次/d,餐中或餐后立即服用,连服7 d,停药3周为1个疗程。结果治疗组和对照组总有效率比较,差异有统计学意义(χ2=14.568,P<0.005)。结论伊曲康唑联合局部抗真菌药物蟹黄肤宁软膏治疗花斑癣,疗效显著,安全性好。     

注射用伊曲康唑与5%葡萄糖存在配伍禁忌

真菌感染病人临床上常应用伊曲康唑注射液治疗,护士在配药过程中,发现伊曲康唑与5%葡萄糖有配伍禁忌。现介绍如下。1临床资料1例真菌感染病人,护士遵医嘱将伊曲康唑注射液30mL加入5%葡萄糖250mL中,液体即刻呈乳白色。立即通知医生,更换药物。2实验取伊曲康唑与5%葡萄糖各1mL混合,液体立即呈乳白色,振荡后不消失。3小结注射用伊曲康唑与5%葡萄糖有配伍禁忌,临床护士应注意观察,不断积累经验,完善药物配伍禁忌表的内容,用药前认真阅读药物使用说明书,以避免不必要的损失,保证安全用药。(收稿日期:2007-02-13;修回日期:2007-07-22)(本文编辑…     

伏立康唑与伊曲康唑序贯治疗血液病侵袭性真菌感染的临床疗效及安全性观察

【目的】观察分析应用伏立康唑与伊曲康唑序贯治疗恶性血液病侵袭性真菌感染患者的疗效及安全性。[A-法】选择本院收治的43例恶性血液病侵袭性真菌感染患者的临床资料,采用伏立康唑与伊曲康唑序贯治疗的方法,先给予伏立康唑注射液,再口服伊曲康唑进行序贯治疗,1～2周作为一个疗程。观察伏立康唑与伊曲康唑序贯治疗的临床疗效及不良反应发生情况。【结果143例患者中确诊6例（14．O％）,临床诊断16例（37．2％）,拟诊21例（48．8％）。经伏立康唑与伊曲康唑序贯治疗后,痊愈9例（20．9％）,显效20例（46．5％）,进步7例（16．3％）,无效7例（16．3％）,总治疗有效率为67．4％（29／43）;其中确诊患者治疗有效率为50．0％（3／6）,临床诊断患者有效率为68．8％（11／16）,拟诊患者有效率为41．4％（15／21）;患者出现轻微程度的恶心呕吐、头痛、视觉障碍、腹泻、下肢肿胀共计15例,不良反应发生率为34.8％。3例（7％）患者出现轻微肝功能损伤,血清肌酐水平升高2例（4．6％）,谷丙转氨酶（GPT）／谷草转氨酶（GOT）升高1例（2．3％）,以上患者予以保肝治疗后肝功能恢复正常。【结论】伏立康唑与伊曲康唑序贯治疗恶性血液病侵袭性真菌感染临床疗效确切,不良反应低,可为此类患者临床合理安全用药提供新的借鉴。     

Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies

Invasive fungal infection remains the most common cause of infectious death in acute leukemia. In this open-label, randomized study, we compared the efficacy and safety of caspofungin with that of intravenous itraconazole for antifungal prophylaxis in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Of 200 patients, 192 were evaluable for efficacy (86 for itraconazole, 106 for caspofungin). Duration of prophylaxis (median, 21 days [range, 1 to 38 days]), demographics, and prognostic factors were similar in both groups. Ninety-nine patients completed antifungal prophylaxis without developing fungal infection (44 [51%] with itraconazole, 55 [52%] with caspofungin). Twelve patients developed documented invasive fungal infections, five in the itraconazole group (four with candidemia and one with Aspergillus pneumonia), and seven in the caspofungin group (two with candidemia, two with disseminated trichosporon species, two with Aspergillus pneumonia, and one with disseminated Fusarium spp). Two patients in the itraconazole group and four in the caspofungin group died of fungal infection (P = 0.57). Grade 3 to 4 adverse event rates were comparable between groups; the most common event in both was reversible hyperbilirubinemia. No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60. In conclusion, intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy, and both drugs were well tolerated.     

伊曲康唑注射液在血液肿瘤患者经验性抗真菌治疗的临床研究

本研究回顾分析了35例接受化疗或造血干细胞移植的血液肿瘤患者用伊曲康唑进行经验性抗真菌治疗的疗效,探讨其在侵袭性真菌感染中经验性治疗的有效性及安全性。根据IDSA指南推荐,对于使用广谱抗生素治疗4 d以上无效的发热患者,使用伊曲康唑注射液进行经验性抗真菌治疗。结果显示,接受伊曲康唑注射液经验性治疗的35例患者的临床总有效率为62.9%(22/35),联合终点治疗成功率为54.3%(19/35),不良反应事件有6例(17.1%),因不良反应停药2例(5.7%)。进一步分析表明,发热早期(<5 d)使用伊曲康唑经验性治疗反应率更高(P=0.031),临床拟诊患者伊曲康唑治疗有效率明显高于临床诊断及确诊患者(P=0.002),粒细胞缺少期使用唑类预防对伊曲康唑经验性治疗疗效无显著影响(P=0.054)。结论:伊曲康唑注射液是一种安全有效的抗真菌药,在血液肿瘤患者中可以作为经验性抗真菌治疗的首选。     

Efficacy and safety of intravenous voriconazole and intravenous itraconazole for antifungal prophylaxis in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome

Purpose

To compare the efficacy and safety of voriconazole with itraconazole as prophylaxis in leukemia patients.

Methods

Open-label, randomized study. Patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing induction chemotherapy or first salvage were eligible. Patients received voriconazole (400?mg intravenous (IV) every 12?h for two doses, followed by 300?mg BID) or itraconazole (200?mg IV twice daily for 2?days, followed by 200?mg IV daily).

Results

A total of 127 patients were enrolled. Four were excluded because they did not receive study drug (n?=?3) or received two antifungal agents during the first week on study (n?=?1), leaving 123 patients for analysis. None of the 71 patients receiving voriconazole developed proven or probable invasive fungal infection, compared to two (4%) of the 52 patients receiving itraconazole (P?=?0.17). Drug discontinuation because of adverse events occurred in 15 patients (21%) receiving voriconazole and six (11%) receiving itraconazole (P?=?0.23).

Conclusions

Voriconazole is a good alternative for prophylaxis in patients with leukemia. Elevated baseline bilirubin levels were associated with a higher risk of side effects in patients receiving IV voriconazole or IV itraconazole. Monitoring of liver function and drug levels should be considered for some patients.     

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。     

Clinical efficacy and safety of intravenous itraconazole in the management of invasive candidiasis in patients of surgery and critical care

Although itraconazole exhibits potent activity against Candida species, there have been few studies examining the use of intravenous itraconazole in the treatment of invasive candidiasis. A nationwide multicenter clinical study was conducted to evaluate the efficacy and safety of intravenous itraconazole in the management of invasive candidiasis, including non-albicans Candida species, in non-neutropenic patients undergoing surgery and critical care. Between September 2007 and August 2009, patients with proven and presumed candidiasis were enrolled at 22 participating institutions. Patients with presumed candidiasis had a deep-body temperature of 37.8°C or higher and were positive for serum β-D: -glucan or two or more colonization sites of Candida species. The main exclusion criterion was severe renal impairment (creatinine clearance <30 ml/min). The primary efficacy analysis was based on clinical and microbiological responses 5-10 days after the end of treatment, assessed by an independent data review committee. Of the 60 patients enrolled, 49 were included in the modified intention-to-treat population; 31 patients received a definitive diagnosis and 18 patients a presumed diagnosis. Intravenous itraconazole was used as first-line therapy to treat 39 patients and as second-line therapy for 10 patients. The isolated species included Candida albicans (25 strains with definitive diagnosis and 17 with presumed diagnosis) and non-albicans species (16 and 10, respectively). Treatment was successful in 61.5% patients (65.5% in first-line and 50.0% in second-line therapy); 60% of proven invasive candidiasis (IC) patients were judged as successful compared with 63.2% of presumed candidiasis patients. Eradication rate was 63.6% for C. albicans and 71.4% for C. glabrata. Adverse effects occurred in 9 of 60 patients (15.0%), commonly impaired liver function. The clinical efficacy and safety of intravenous itraconazole were suggested in the management of proven and presumed candidiasis including C. glabrata in non-neutropenic patients. The status of intravenous itraconazole in the Japanese guideline warrants reconsideration.     

Intravenous itraconazole.

OBJECTIVE: To review the pharmacology, mycology, chemistry, pharmacokinetics, efficacy, safety, tolerability, dosage, administration, and economic issues of intravenous itraconazole. DATA SOURCES: A MEDLINE search from 1978 to June 2000 of the English-language literature and an extensive review of meeting abstracts was conducted. Due to the paucity of published information concerning the pharmacokinetics, efficacy, and safety of the intravenous formulation of intravenous itraconazole, additional information was obtained from the manufacturer. DATA EXTRACTION: Data from in vitro and preclinical studies, as well as Phase II and III clinical trials, were included. DATA SYNTHESIS: The triazole antifungal agent itraconazole is available in a cyclodextrin-based intravenous formulation. Intravenous itraconazole is indicated for the treatment of pulmonary and extrapulmonary blastomycosis; histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis; and pulmonary and extrapulmonary aspergillosis in patients who are intolerant of or who are refractory to amphotericin B. This formulation provides quicker and more consistent therapeutic concentrations than the oral formulations. Clinical data comparing the efficacy of intravenous itraconazole with that of amphotericin B are lacking. CONCLUSIONS: Intravenous itraconazole offers a less toxic alternative for patients with pulmonary and extrapulmonary blastomycosis, histoplasmosis, and aspergillosis who cannot receive oral medications or who are intolerant of or refractory to amphotericin B.     

Pharmacokinetics and safety of a 7-day administration of intravenous itraconazole followed by a 14-day administration of itraconazole oral solution in patients with hematologic malignancy

The pharmacokinetics and safety of an intravenous hydroxypropyl-beta-cyclodextrin solution of itraconazole administered for 7 days followed by itraconazole oral solution administered at 200 mg once or twice daily for 14 days were assessed in 17 patients with hematologic malignancies. Steady-state plasma itraconazole concentrations were reached by 48 h after the start of intravenous treatment. The mean trough plasma itraconazole concentration at the end of the intravenous treatment was 0.54 +/- 0.20 microg/ml. This concentration was not maintained during once-daily oral treatment but increased further in the twice-daily treatment group, with a trough itraconazole concentration of 1.12 +/- 0.73 microg/ml at the end of oral treatment. As expected in the patient population studied, all patients experienced some adverse events (mainly gastrointestinal). Biochemical and hematologic abnormalities were frequent, but no consistent changes occurred. In conclusion, 7 days of intravenous treatment followed by 14 days of twice-daily oral treatment with itraconazole solution enables plasma itraconazole concentrations of at least 0.5 microg/ml to be reached rapidly and to be maintained. The regimen is well tolerated and has a good safety profile.     

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.     

An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia

OBJECTIVES: This trial studied the efficacy and safety of itraconazole and fluconazole in the prevention of invasive fungal infections in neutropenic patients with haematological malignancies. PATIENTS AND METHODS: An 8 week, open-label, randomized, parallel-group, multicentre trial comparing itraconazole oral solution (2.5 mg/kg twice daily; N=248) with fluconazole oral solution or capsules (400 mg daily; N=246) in 494 patients with anticipated profound neutropenia (i.e. neutrophil count expected to be <500 cells/mm3 for at least 10 days) from tertiary care centres. RESULTS: Invasive fungal infections were reported for 4 out of 248 patients (1.6%) in the itraconazole group and 5 out of 246 patients (2.0%) in the fluconazole group. Invasive Aspergillus infections were proven for 2 out of 248 patients (0.8%) in the itraconazole group and 3 out of 246 patients (1.2%) in the fluconazole group. For both the ITT and profoundly neutropenic populations, no differences were detected between treatment groups in proven or suspected invasive fungal infections or other endpoints. The mortality rates owing to proven invasive fungal infections were 2 out of 248 patients (0.8%) for the itraconazole group and 3 out of 246 patients (1.2%) for the fluconazole group. There was also no difference between treatment groups in the number of patients who recovered from neutropenia or in the duration of neutropenia. More discontinuation of drug intake owing to nausea and more hypokalaemia occurred in the itraconazole group, other adverse events and the total number of adverse events were similar in both groups. CONCLUSIONS: In this study there were no differences in the efficacy and safety of itraconazole and fluconazole prophylaxis in neutropenic patients with haematological malignancies.     

Serum itraconazole concentrations and clinical responses in Candida-associated denture stomatitis patients treated with itraconazole solution and itraconazole capsules

The aim of this study was to compare the concentrations of itraconazole in serum and saliva after treatment with itraconazole cyclodextrin solution or itraconazole capsules in Candida-associated denture stomatitis patients without evidence of immunodeficiency. Forty patients were randomly assigned to receive either itraconazole cyclodextrin solution or itraconazole capsules, both at a dosage of 100 mg bd for 15 days. On completion of treatment palatal erythema was assessed and an oral rinse and imprint cultures were collected. Serum and saliva samples were collected at the same time and itraconazole concentrations measured using reverse-phase high-performance liquid chromatography. Itraconazole susceptibilities of Candida albicans and Candida glabrata strains isolated at baseline were measured by a broth microdilution method. Serum itraconazole concentrations achieved did not differ significantly between the two preparations (P = 0.39) although a significantly higher number of patients in the itraconazole cyclodextrin group (P < 0.001) had detectable levels of itraconazole in their saliva compared with the capsule group. Mycologically cured patients had slightly, though not significantly (P = 0.28), higher serum itraconazole concentrations than those from whom yeasts were not eradicated. It was concluded that both formulations of itraconazole were equally effective in treatment of denture stomatitis. Among immunocompetent patients, the absorption of the liquid preparation is no greater than that of the capsules. Therapeutic success in this group was achieved with lower serum itraconazole concentrations than have been reported for immunocompromised groups.