常用抗真菌药物治疗新型隐球菌性脑膜炎的疗效对比

新型隐球菌性脑膜炎是隐球菌属中某些变异菌侵犯中枢神经系统的一种深部真菌感染。传统治疗药物有氟胞嘧啶、两性霉素B、氟康唑及伊曲康唑,近年来。为了降低两性霉素B的毒性并提高其疗效,研制出两性霉素B脂质体。对上述抗真菌药物作用机制、药动学、临床疗效及不良反应的对比分析,可为临床新型隐球菌性脑膜炎更合理、更安全、更有效的治疗提供参考。     

Itraconazole维持治疗艾滋病患者的隐球性脑膜炎

隐球性脑膜炎是艾滋病患者的一种致命性机会感染,所以在选择性联合应用两性霉素B与氟胞嘧啶后必须给予维持治疗。作者使用伊曲康唑(itraconazole),以防止艾滋病患者的隐球菌性脑膜炎。研究对象为5例抗人免疫缺陷病毒抗体阳性的患者。所有患者均从脑脊液中培养中分离出隐球菌性新型细球菌。每例均接受诱导治疗(每日静注两性霉素B 0.3mg/kg;每日口服氟胞嘧啶150mg/kg)6～8周。4例维持治疗口服伊曲康唑100mg,每日2次;     

伴有爱滋病隐球菌性脑膜炎患者脑脊液中的两性霉素B浓度

对伴有爱滋病(AIDS)的隐球菌性脑膜炎最理想的临床治疗措施尚不清楚。但不具AIDS的此类疾病,传统疗法联用两性霉素B和氟胞嘧啶进行治疗。其原因之一是两性霉素B对脑部穿透力较差,氟胞嘧啶能迅速通过血脑屏障。但因氟胞嘧啶具有骨髓抑制作用,从而限制它在伴有爱滋病隐球菌性脑腹炎患者中的应用。因此有些医生仅单用两性霉素B来治疗上述疾病。由于隐球菌性脑腹炎患者经常复发,因     

伊曲康唑注射液治疗老年人侵袭性肺曲霉病

目的:研究伊曲康唑注射液治疗老年人侵袭性肺曲霉病的临床疗效及安全性。方法:对15例60 a以上应用伊曲康唑治疗的侵袭性肺曲霉病病人的资料进行分析。其中男性11例,女性4例,年龄(72±s 7)a;确诊病例3例,临床诊断很可能病例8例,临床诊断可能病例4例。伊曲康唑注射液d 1～2,每日400mg,分2次静脉滴注,以后200 mg·d-1静脉滴注。观察临床疗效、用药时间、预后及不良反应。结果:总有效率60％(9／15)。3例确诊病例中显效1例,进步1例,无效1例。临床诊断很可能病例中痊愈2例,显效2例,无效4例。临床诊断可能病例中痊愈3例,显效1例。曲霉菌完全清除9例,真菌交替3例,未清除3例。不良反应为头痛1例。结论:早期、足量、足疗程应用伊曲康唑注射液治疗老年人侵袭性肺曲菌病疗效好,安全。     

伊曲康唑与氟康唑在重症监护室早期经验性治疗真菌感染的疗效比较

目的比较伊曲康唑和氟康唑在重症监护室早期经验性治疗中的有效性和安全性。方法采取随机、对照、开放的临床试验，入选的40例患者具有真菌感染的高危因素，均出现不明原因发热，广谱抗生素治疗3～7 d无效。将入选患者随机分配为伊曲康唑治疗组和氟康唑治疗组各20例。伊曲康唑治疗组给予伊曲康唑注射液200 mg，q12 h，先治疗2 d，随后给予200 mg，qd，共5 d，再改用伊曲康唑口服液口服，每次200 mg，bid，治疗14 d；氟康唑治疗组给予氟康唑注射液400 mg静脉滴注，qd，共治疗21 d。观察患者体温变化、真菌感染情况、药物相关的不良反应和疗效。结果伊曲康唑组总有效率65.0%，不良反应率30.0%；氟康唑组总有效率50.0%，不良反应率5.0%，但两组总有效率和不良反应发生率均差异无显著性（均P＞0.05）。治疗过程中，氟康唑组出现2例深部真菌感染。结论伊曲康唑和氟康唑均可作为现阶段重症监护室早期经验性治疗的一线药物，但伊曲康唑疗效更佳。     

回顾性分析新型隐球菌性脑膜炎的诊断与治疗

目的 分析隐球菌性脑膜炎临床资料并探讨隐球菌性脑膜炎的诊断与治疗。方法 总结近8年来本院隐球菌性脑膜炎的诊断、治疗和预后情况。结果 23例患者中有6，3，2，2例分别误诊为结核性脑膜炎、病毒性脑膜炎、血管炎、系统性红斑狼疮脑病。比较氟康唑和两性霉素B联用与两性霉素B和氟胞嘧啶联用，其治疗痊愈率无明显差别。结论 隐球菌脑膜炎误诊率较高，建议对可疑病例做反复腰穿、墨汁涂片和霉菌培养。     

两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并中枢神经系统新型隐球菌病的疗效分析

目的：观察两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并中枢神经系统新型隐球菌病的疗效。方法24例艾滋病合并中枢神经系统新型隐球菌病患者,随机分为观察组和对照组,各12例,观察组患者使用两性霉素B联合氟胞嘧啶与伏立康唑进行治疗,对照组患者使用两性霉素B联合氟胞嘧啶进行治疗,比较两种治疗方式的临床疗效、患者的不良反应及患者的死亡率。结果经过治疗后观察组患者的治疗效果优于比对照组,比较差异具统计学意义（P〈0.05）。在不良反应和死亡率上两组比较差异无统计学意义（P〉0.05）。结论针对艾滋病合并中枢神经系统新型隐球菌病患者采用两性霉素B联合氟胞嘧啶与伏立康唑进行治疗,临床治疗效果更为显著,可明显减轻患者痛苦及改善临床症状。     

恶性血液病肺部真菌感染疗效观察

目的 探讨恶性血液病合并肺部真菌感染临床治疗效果.方法 46例恶性血液病合并肺部真菌感染患者,经药敏试验测定后选伊曲康唑治疗.第1～2天使用伊曲康唑,静脉滴注给予200 mg,2次/d,第3天开始,直至用药2周,同样静脉滴注给予伊曲康唑200 mg,1次/d,治疗有效患者2周后给予伊曲康唑口服液,每次200 mg,2次...     

新生儿真菌感染的药物治疗

新生儿深部真菌感染近年逐渐增多,若不及时诊治将直接威胁到新生儿的健康乃至生命。本文对新生儿深部真菌感染的药物治疗进行全面介绍,并按类别详细分述了两性霉素B、氟康唑、伊曲康唑、5-氟胞嘧啶、卡泊芬净的临床应用。     

特比萘芬与伊曲康唑治疗甲癣疗效的Meta分析(英文)

目的:比较特比萘芬与伊曲康唑治疗甲癣疗效的差异。方法:检索Medline等数据库,查找所有比较特比萘芬9伊曲康唑治疗18～60 a无系统疾病所患甲癣的双盲随机对照试验的文献,记录这2种药物治疗甲癣的真菌学治愈率并对其进行汇总分析,得出合并后真菌学治愈率的优势比(OR)及其95％的可信区间(CI)。结果:经筛选,共得到6篇符合标准的双盲随机对照试验;特比萘芬250 mg·d-1连续疗法组的真菌学治愈率高于伊曲康唑400 mg·d-1冲击疗法[OR=5．01,95％CI(3．42～7．33)]和伊曲康唑200 mg·d-1连续疗法[OR=2．58,95％CI(1．91～3．49)]。结论:特比萘芬治疗甲癣的疗效优于伊曲康唑。     

Cryptococcal Meningitis in Patients with the Acquired Immunodeficiency Syndrome

The optimum therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS) remains unresolved. Traditional therapy consists of amphotericin B with or without flucytosine. Obstacles exist in administering these agents to patients with AIDS. Mortality rates during initial therapy are relatively high. Given the lack of proved benefit, we do not recommend adding flucytosine to amphotericin B routinely. The search for more efficacious and less toxic agents continues. The oral triazoles, especially fluconazole, have increased the options for treatment of this disease. New strategies and novel approaches in managing cryptococcal meningitis in patients with AIDS continue to be developed.     

Treatment of cryptococcal meningitis with five anti-fungal drugs: the role of amphotericin B

Experiments are described of the treatment of two patients with cryptococcal meningitis using antifungal drugs and amphotericin B. The first patient was a 56-year-old man with a slight azotaemia caused by hypertensive nephrosclerosis. Lumbar puncture revealed a positive India ink stain and a positive culture for Cryptococcus neoformans; serum titre for cryptococcal antigen was elevated. Amphotericin B was not administered because of the patient's slight azotaemia. After admission, the patient received oral and intravenous fluconazole (400 mg per day), for a total dose of 40 g of fluconazole over 103 days from October 1 while simultaneously receiving treatment with oral itraconazole (200 mg per day) from October 1 to December 5. In addition, he was given intravenous miconazole (600-1000 mg per day, total 74.4 g) and intrathecal miconazole (5-20 mg per day, total 375 mg) from December 1 to March 4 1990. Concomitantly, oral flucytosine (6 g per day) was given from December 5 to March 1 1990. Lumbar puncture performed at the completion of these treatments indicated the India ink stain still was positive and the serum titre for cryptococcal antigen high. Finally, amphotericin B alone was administered to the patient intravenously and intrathecally from March 4 to May 1, with an initial dose of 5 mg i.v. gradually increasing by 5 mg increments up to 50 mg per day. The patient's clinical symptoms immediately improved; the India ink stain became negative for the first time after admission and the serum titre for cryptococcal antigen also gradually decreased. On May 1, the patient was completely cured of cryptococcal meningitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of cryptococcal meningitis in patients with AIDS

A case of cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome (AIDS) is described, as well as the epidemiology, pathogenesis, clinical manifestations, diagnosis, and therapeutic management of the disease. In July 1987 a 38-year-old white man was admitted to the hospital because of confusion, disorientation, and headache. His medical history was notable for a positive human immunodeficiency virus test. Culture of the cerebrospinal fluid was positive for Cryptococcus neoformans. The patient was started on amphotericin B 16 mg/day (0.3 mg/kg/day) intravenously and flucytosine 2 g every six hours (150 mg/kg/day) orally. Despite premedication with diphenhydramine and acetaminophen, he experienced rigors that were treated with hydrocortisone and meperidine. Three weeks later he was discharged on flucytosine 2 g orally every six hours and amphotericin B 50 mg intravenously every other day. One week later the patient developed fever and chills; blood cultures were positive for methicillin-sensitive Staphylococcus aureus, and his peripheral leucocyte count was 1.8 X 10(3)/cu mm. Flucytosine was discontinued, and he was treated with intravenous nafcillin while remaining on amphotericin B. In October the patient complained of nausea, vomiting, weakness, and agitation. A CSF latex agglutination titer for cryptococcal antigen was 1:32. He was treated with amphotericin B 50 mg daily until symptoms resolved and then continued on amphotericin B 50 mg twice weekly. Cryptococcosis is the most common life-threatening fungal infection among AIDS patients. In contrast to immunocompetent hosts, this population invariably develops disseminated disease, with 85% having meningeal involvement. The most effective therapy for cryptococcal meningitis in patients with AIDS has not been established.(ABSTRACT TRUNCATED AT 250 WORDS)     

伊曲康唑治疗血液病合并真菌感染30例

目的观察伊曲康唑治疗血液病合并真菌感染的疗效与安全性。方法选择医院2005年1月至2007年12月血液病合并侵袭性真菌感染患者30例,应用伊曲康唑序贯治疗。第1-2天200mg／次、2次／d静脉注射,第3-14天200mg／次、1次／d静脉注射,有效者第15天起改用伊曲康唑口服液200mg／次、2次／d,总疗程14～90d。结果痊愈8例,显效11例,进步4例,无效7例,总有效率为63．33％（19／30）;不良反应发生率16．67％（5／30）,主要表现为胃肠道反应、肝功能损害、皮疹、水肿,均为一过性。结论伊曲康唑治疗血液病合并真菌感染安全有效。     

Antifungal combination therapy: clinical potential

Combination antifungal therapy has been an area of research and clinical interest since systemic antifungals became available decades ago. In vitro and clinical data were generated for some of the more common invasive fungal infections, especially candidiasis, but until very recently few clinical studies were performed. The first invasive fungal infection to be examined in clinical trials with adequate statistical power was cryptococcal meningitis and several of these trials stand out as classical studies in the clinical evaluation of combination antifungal therapy. More recently, since the availability of the newer antifungal agents, including the echinocandins and extended-spectrum triazoles, there has been a growing interest in examining combination antifungal therapy for invasive fungal disease, especially invasive aspergillosis. This is by no means a comprehensive review of all existing experimental data. Instead, the focus is on the clinical data that have been generated to date and on providing insights into potential future clinical directions. For instance, recent clinical data for cryptococcosis confirm that amphotericin B plus flucytosine is the most active combination for patients with cryptococcal meningitis. A recently completed clinical trial in candidaemia suggests a trend towards improved outcomes among patients receiving amphotericin B plus fluconazole versus fluconazole alone. In aspergillosis, several experimental models suggest benefit of a variety of antifungal combinations, but have not been confirmed in prospective clinical trials. Ultimately, the goal is to provide the reader with a comprehensive but useful review to this complicated and often confusing therapeutic dilemma.     

Cryptococcal meningitis: diagnosis and treatment

In the last decade, largely due to the increasing number of immunocompromised patients, particularly those with AIDS, there has been a dramatic increase in the incidence of cryptococcosis. The majority of human cryptoccoccal infections are caused by C. neoformans. Pulmonary cryptococcosis is the commonest form of infection and meningitis is the most severe, being fatal in most cases. Diagnosis is usually by culture and/or serology. Combined therapy with amphotericin B and flucytosine remains the initial treatment of choice, although a short course of amphotericin B alone followed by high dose fluconazole or itraconazole and the combination of flucytosine with fluconazole or with itraconazole may be effective alternatives. Both azoles, given as single agent maintenance therapy, have been shown to be beneficial as they are more effective and less toxic than the weekly infusion of amphotericin B. Primary prophylaxis with fluconazole has been advocated but problems of resistance are a concern. To date, itraconazole has not been associated with problems of resistance.     

Antifungal agents used in systemic mycoses. Activity and therapeutic use

The development of the polyene antibiotic, amphotericin B, provided for the first time a drug which was clinically effective in many serious mycotic diseases. Unfortunately, it requires parenteral administration and is often toxic, factors which limit the total cumulative dose which can be given. Efforts to utilise combinations of amphotericin B with other agents were best realised with amphotericin B/flucytosine in cryptococcal meningitis, and to a lesser degree in systemic candidiasis. More recently, the introduction of new imidazoles has extended the range of applications of these drugs to fungal diseases. Two members of this group, miconazole and ketoconazole, are promising agents. Miconazole is a parenterally administered agent for patients acutely ill with candidiasis and other mycotic infections. It may be the drug of choice for Petriellidium boydii infections and it is an attractive alternative to amphotericin B for intrathecal administration to patients with fungal meningitis. Ketoconazole offers much less toxicity, the advantage of oral administration, and the possibility of indefinitely prolonged therapy. However, it does not attain high concentrations in either the urine or cerebrospinal fluid. With the imidazoles, we have entered a new era of antifungal therapy which may produce even better antifungal agents than those currently available.     

Treatment of acute cryptococcal disease

Successful treatment outcome for cryptococcal disease has been available since the introduction of the polyene antifungal, amphotericin B. Over the past 15 - 20 years, treatment of acute cryptococcal disease has dramatically improved. Several therapeutic strategies have been introduced which improve overall outcome of therapy and help decrease the duration of treatment. Not surprisingly, most data now exists on the treatment of AIDS-associated cryptococcal disease, especially cryptococcal meningitis. Currently, amphotericin B with or without flucytosine is regarded as the best initial therapy for patients with meningitis or more severe illness, although, the azoles and other formulations of amphotericin B can considered in other situations. The choice of treatment for cryptococcal disease depends on both the anatomic sites of involvement and the host’s immune status, all of which will be addressed in this article.     

Treatment of acute cryptococcal disease

Successful treatment outcome for cryptococcal disease has been available since the introduction of the polyene antifungal, amphotericin B. Over the past 15-20 years, treatment of acute cryptococcal disease has dramatically improved. Several therapeutic strategies have been introduced which improve overall outcome of therapy and help decrease the duration of treatment. Not surprisingly, most data now exists on the treatment of AIDS-associated cryptococcal disease, especially cryptococcal meningitis. Currently, amphotericin B with or without flucytosine is regarded as the best initial therapy for patients with meningitis or more severe illness, although, the azoles and other formulations of amphotericin B can considered in other situations. The choice of treatment for cryptococcal disease depends on both the anatomic sites of involvement and the host's immune status, all of which will be addressed in this article.     

Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity

The study investigated the oral absorption of two anti-fungal agents, fluconazole and itraconazole, under conditions of low intragastric acidity. Twelve healthy male volunteers received each of 4 dosing regimens: 200 mg itraconazole alone, 200 mg itraconazole and famotidine, 100 mg fluconazole alone, and 100 mg fluconazole and famotidine. Two oral doses of 40 mg famotidine were used to induce hypochlorhydria. Serum drug concentrations were measured (by high pressure liquid chromatography) for 48 h after a single dose of each anti-fungal agent. When dosed with famotidine, there was a significant 52.9% decrease of the peak intraconazole concentration (P < 0.011), and a significant 51.1% decrease of the 48-h integrated serum intraconazole concentration (P= 0.005). Famotidine-induced hypochlorhydria did not affect the absorption of fluconazole.