临床药师参与1例新型隐球菌性脑膜炎抗真菌治疗的病例分析

目的:探讨临床药师在新型隐球菌性脑膜炎患者抗真菌治疗中的药学服务方法。方法:临床药师参与1例新型隐球菌性脑膜炎患者的药物治疗过程,从协助医师优化抗真菌药物治疗方案、对患者进行药学监护、不良反应处理及用药教育等方面提供药学服务。使用两性霉素B期间,患者出现顽固性低钾血症,临床药师建议医师降低两性霉素B剂量,加用伏立康唑抗真菌治疗。结果:调整抗真菌治疗方案后,患者未再出现低血钾;经系统抗真菌治疗11周后,患者病情较前明显好转。结论:临床药师参与新型隐球菌性脑膜炎抗真菌治疗的心得是:遵循指南,但不失灵活处理;主动服务,细节保障用药安全。     

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。     

36例新型隐球菌性脑膜炎的临床分析

目的 探讨36例新型隐球菌性脑膜炎的临床特征，以提高对该病的认识。方法 分析36例新型隐球菌感染患者的临床资料。结果 新型隐球菌感染的患者临床表现均有不同程度的头痛、颅内压增高表现，葡萄糖降低尤为显著，IgG、IgM、IgA及微量总蛋白升高明显。治疗后脑脊液和血清标本中隐球菌荚膜多糖抗原滴度下降明显。新型隐球菌对两性霉素B(100%)、氟康唑(94.4%)和5-氟胞嘧啶(94.4%)抗真菌药敏感性较高。结论 对颅内压增高、脑膜刺激征阳性的患者反复多次进行脑脊液培养、墨汁染色和隐球菌荚膜多糖抗原检测，有助于新型隐球菌性脑膜炎的早期诊断和早期治疗；隐球菌荚膜多糖抗原滴度随着患者病情的好转而下降。两性霉素B联合氟康唑或5-氟胞嘧啶治疗新型隐球菌性脑膜炎仍然安全有效；早期控制感染和降低颅内压是治疗的关键。     

两性霉素B脂质体鞘内注射治疗新型隐球菌性脑膜炎疗效观察

目的：探讨两性霉素B鞘内注射治疗新型隐球菌性脑膜炎的可行性。方法：将常规静脉注射两性霉素B后、病情仍难以控制的（脑脊液中新型隐球菌性仍难以转阴,颅内高压持续不降）24例新型隐球菌性脑膜炎患者,随机分为两性霉素B鞘内注射组、两性霉素B脂质体鞘内注射组,鞘内注射剂量从0.1 mg开始,逐渐增加剂量,直到出现难以耐受的不良反应或每次注射剂量达到1 mg。结果：患者可以较好地耐受两性霉素B脂质体鞘内注射,鞘内注射两性霉素B脂质体发生不良反应的几率及严重程度明显低于普通两性霉素B。结论：两性霉素B脂质体鞘内注射治疗新型隐球菌性脑膜炎具有可行性。     

两性霉素B对艾滋病伴隐球菌性脑膜炎患者的临床治疗及其护理对策

目的:分析两性霉素B对艾滋病伴隐球菌性脑膜炎患者的临床治疗及其护理对策,为艾滋病伴隐球菌性脑膜炎的临床治疗提供参考。方法:选取2014年1月—2015年12月间收治的艾滋病伴隐球菌性脑膜炎患者8例,在采用两性霉素B治疗期间,并给予优质护理,即在治疗前、治疗期间和治疗后给予心理护理,并采用中心静脉置管术建立静脉通路,用药过程中发生药物不良反应给予相应措施护理。结果:经两性霉素B和相应支持治疗和优质护理的8例艾滋病伴隐球菌性脑膜炎患者,治愈为4例,好转为2例,另2例(1例因抗隐球菌等疗效不佳而自动出院,1例因隐瞒隐球菌性脑膜炎病史而导致延迟治疗而效果不佳,其治疗总有效率为75.00%。结论:采用两性霉素B治疗艾滋病伴隐球菌性脑膜炎患者,治疗期间配以优质护理,能减轻艾滋病伴隐球菌性脑膜炎患者的痛苦,缩短了疗程和提高临床疗效。     

两性霉素B对小儿隐球菌性脑膜炎的临床观察

目的　观察两性霉素 B对小儿隐球菌性脑膜炎的临床疗效。方法　 32例小儿隐球菌性脑膜炎患者 ,男 2 5例 ,女 7例 ,年龄 0 .5～ 1 1岁 ,给予两性霉素 B,静脉滴注 ,疗程为 3个月。结果　两性霉素 B对小儿隐球菌性脑膜炎疗效满意 ,总有效率 93.8%。     

临床药师参与1例新型隐球菌脑膜炎患儿治疗的药学实践

目的:探讨临床药师如何在新型隐球菌性脑膜炎患儿抗真菌治疗中进行药学实践。方法:临床药师参与1例新型隐球菌性脑膜炎儿童的药物治疗过程,从抗菌药物方案制定、给药剂量确定、疗效监护及不良反应处理等方面提供全程化的药学监护。结果:抗真菌治疗期间,患儿出现肾功能损害及低钾血症,临床药师建议医师降低两性霉素B剂量,停用甘露醇、呋塞米以避免加重肾功能损害,同时予以补钾治疗。调整治疗方案后,患儿肾功能恢复正常、未再出现低血钾。经系统抗真菌治疗,患儿病情较治疗前明显好转。此外,临床药师对维持治疗的抗真菌药物的选择给出药学建议,并被临床医师采纳。结论:临床药师全程参与新型隐球菌脑膜炎患儿的监护,为其治疗方案及不良反应的处理提供药学建议,对合理、安全的使用药物起到了良好作用,体现了药学服务的价值。     

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     

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。     

高剂量氟康唑对AIDS患者隐球菌性脑膜炎的抢救治疗

隐球菌性脑膜炎在AIDS患者中是威胁生命的感染,隐球菌性脑膜炎在AIDS病人的所有机会性感染中占5%～10%,即使采用常规疗法治疗AIDS患者该真菌感染的复发率还是高,4个月内复发接近34%,因此大部分病人采用抑制疗法来控制感染,但是复发还会发生。三唑氟康唑(Fluconazole)治疗隐球菌性脑膜炎显示出前景,并且较两性霉素B呈现出较好的耐受性。氟康唑较两性霉素B有     

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.     

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)     

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.     

隐球菌性脑膜炎患者真菌培养结果分析及潜在意义

目的探讨真菌培养结果对隐球菌性脑膜炎诊疗的意义。方法回顾性分析了隐球菌患者的脑脊液培养结果及印度墨汁染色结果,将两者对照研究。结果 45例隐球菌性脑膜炎患者首次脑脊液培养结果43例阳性,虽然高于印度墨汁染色38例阳性的结果,但差异无统计学意义（χ2=1.975,P=0.157）;治疗中期脑脊液培养结果30例为阳性,和印度墨汁染色的结果比较未见差异（χ2=1.661,P=0.195）;首次脑脊液培养结果显示26例患者对氟康唑耐药而未见对两性霉素B耐药者（χ2=33.804,P=0.000）;治疗末期脑脊液培养的结果先于印度墨汁染色转阴,10例印度墨汁染色持续阳性患者,脑脊液培养转阴患者停药后未见复发[P（1≤X）=0.002]。结论脑脊液培养对指导隐球菌脑膜炎患者抗真菌药物的使用有重要的价值,需高度重视;培养结果可能更适合作为停药的指标之一。     

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.     

两性霉素B所致肾小管酸中毒的临床分析

目的 :观察长期应用两性霉素B所致肾小管酸中毒 (RTA)的发生率 ,探讨其影响因素及防治原则。方法 :1995年～ 2 0 0 1年间我院应用两性霉素B治疗的隐球菌性脑膜炎病人 5 8例 ,观察其用药前后的临床表现、尿量、尿 pH值以及血、尿电解质变化 ,不典型者通过氯化铵试验证实RTA的存在。结果 :5 8例病人中有 8例发生RTA ,两性霉素B相关性RTA的发生率为 14 % ,出现RTA时累积剂量为 (2 915±s 2 30 4 )mg ,72 8～ 8135mg ,通过两性霉素B减量或停药 ,或者肾毒性药物如甘露醇、磺胺和氨基糖苷类药物的减量或停药 ,可使肾小管酸化功能好转。结论 :RTA的发生和两性霉素B的剂量、肾毒性药物的合用有关。减少或停用上述药物 ,可使肾小管的酸化功能好转     

Fluconazole: a new antifungal agent

The chemistry, activity, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and administration of fluconazole are reviewed. Fluconazole is a triazole antifungal agent labeled for use in the treatment of oropharyngeal and esophageal candidiasis and cryptococcal meningitis. Like the imidazoles, fluconazole inhibits the C-14 demethylation of lanosterol, but it has little or no effect on mammalian cytochrome P-450 enzymes. Fluconazole's activity in vitro does not reflect its effectiveness in vivo. Pharmacokinetic characteristics include water solubility and excellent bioavailability, low protein binding, extensive tissue distribution, and penetration into the cerebrospinal fluid. Fluconazole is eliminated primarily by the kidneys; dosage adjustments are necessary in patients with renal insufficiency. Studies have shown fluconazole to be effective in patients with cryptococcal meningitis and candidiasis, but the superiority of fluconazole over such agents as amphotericin B, ketoconazole, clotrimazole, and itraconazole remains to be proved. Fluconazole has shown varying degrees of success in the treatment of other systemic mycoses. The adverse effects of fluconazole are relatively infrequent and are primarily gastrointestinal. Tolbutamide, warfarin, rifampin, cyclosporine, and phenytoin interact with fluconazole. The drug is available in both oral and intravenous formulations. Fluconazole is a broad-spectrum antifungal drug that appears to be similar in efficacy to other antifungals in the treatment of some systemic mycoses. More studies must be completed before fluconazole can be recommended as a first-line antifungal therapy.