两性霉素B脂质体治疗肺真菌病的疗效及安全性

目的:回顾性调查与分析两性霉素B脂质体治疗真菌感染的疗效及安全性.方法:收集2013年11月-2015年6月我院使用两性霉素B脂质体治疗肺真菌病的病例,以痊愈、显效、进步、无效4种评价标准对其疗效进行评价,并对不良反应进行分析.结果:12例患者中痊愈1例,显效7例,进步1例,无效3例,有效率为66.67％.12例患者均出现不同程度的药物不良反应,仅1例患者因严重肾功能损害停药.结论:两性霉素B脂质体作为肺真菌病的一线治疗药物,疗效可靠,不良反应可控.     

两性霉素B治疗艾滋病合并真菌感染的疗效及不良反应评价

目的:评价两性霉素B治疗艾滋病合并真菌感染的疗效及药品不良反应。方法:收集我院应用两性霉素B治疗艾滋病合并真菌感染的病例,评价总体疗效、患者致病菌分布和用药后清除率及不良反应。结果:共纳入患者89例,其中显效45例,好转32例,无效12例,有效率为86.5%。有76例找到或培养出真菌,其中64株被清除,12株未清除,总体清除率为84.2%。出现不良反应41例(46.1%),其中2例(2.2%)因严重肾功能损害更换用药,其余患者对症处理后均不影响治疗疗程。结论:两性霉素B治疗艾滋病合并真菌感染疗效确切,药品不良反应在可控制范围内。     

两性霉素B治疗血液系统恶性疾病并发深部真菌感染

目的 观察两性霉素B对血液系统恶性疾病并发深部真菌感染的临床疗效及安全性。方法25例恶性血液病患者均使用国产两性霉素B静脉滴注。首次剂量5mg，每天增加5—7．5mg，如能耐受则逐渐增加至治疗剂量25—45mg／d，疗程20—52d。结果24例患者中，16例有效（66．66％）。痊愈11例，显效5例，进步8例。结论两性霉素B抗菌谱较广，且疗效好，为治疗血液系统恶性疾病并发深部真菌感染的高效药物。因其不良反应较大，限制其使用。但只要合理用药，该药仍是一相对较为安全有效的药物。     

两性霉素B脂质体治疗14例肺毛霉菌病患者的疗效观察

目的调查与分析肺毛霉菌病患者应用两性霉素B脂质体的疗效及安全性。方法回顾性分析接受两性霉素B脂质体治疗的14例肺毛霉菌病患者的临床资料。结果 14例患者中5例痊愈,显效7例,进步1例,无效1例,有效率为85.7%。治疗过程中,仅1例在用药10 d出现肾功能损害,减量后症状消失,余均未见严重不良反应。结论两性霉素B脂质体作为肺毛霉菌病的一线药物,疗效可靠,不良反应少,严密观察和调整剂量可使患者疗效满意。     

鞘内注射两性霉素B联合5-氟胞嘧啶治疗小儿细菌性脑膜炎的疗效观察

【摘要】目的：对鞘内注射两性霉素B联合5-氟胞嘧啶治疗小儿细菌性脑膜炎的疗效进行观察和分析。方法：选择2013年3月到2014年3月在本院进行治疗的小儿细菌性脑膜炎60例,随机将其分为观察组和对照组两组各30例,对照组患者给予两性霉素B联合5-氟胞嘧啶治疗,观察组患者则在此基础上给予两性霉素B鞘内注射治疗,对两组患儿治疗后的疗效进行评价和比较。结果：对照组患儿6例显效,12例有效,12例无效,治疗有效率为60.0%,观察组患儿17例显效,12例有效,1例无效,治疗有效率为96.7%,观察组明显高于对照组（P＜0.05）;与对照组相比,观察组患儿的住院时间、体温恢复正常时间以及白细胞恢复正常时间均明显缩短（P＜0.05）。结论：鞘内注射两性霉素B联合5-氟胞嘧啶应用于小儿细菌性脑膜炎的治疗中能够显著提高疗效,对于促进患儿机体的早日康复也具有积极意义,建议在临床上推广应用。     

卡泊芬净治疗老年肺部真菌感染30例

目的调查卡泊芬净治疗肺部真菌感染的疗效及安全性。方法通过回顾性分析,了解卡泊芬净治疗老年肺部真菌感染患者的疗效和不良反应。结果30例患者经卡泊芬净治疗后,痊愈3例,显效5例,进步4例,无效18例,总有效率为26.67%;均未出现明显的不良反应。结论卡泊芬净是治疗老年肺部真菌感染安全有效的药物。     

两性霉素B与氟康唑治疗慢性阻塞性肺疾病并真菌感染效果比较

目的观察两性霉素B与氟康唑治疗慢性阻塞性肺疾病(COPD)合并真菌感染效果比较。方法将我院呼吸内科收治的76例慢性阻塞性肺疾病并真菌感染患者按入院顺序分为对照组38例和治疗组38例;对照组患者给予两性霉素B,治疗组患者给予氟康唑,治疗结束后对比两组患者症状,进行综合效果评价。结果对照组治愈10例(26.3%),有效16例(42.1%),无效12例(31.6%),总有效率为68.4%;治疗组治愈21例(55.3%),有效11例(28.9%),无效6例(15.8%),总有效率为84.2%;治疗组总有效率明显高于对照组,差异有统计学意义。结论氟康唑治疗COPD合并真菌感染具有较好的临床疗效,疗效优于应用两性霉素B。     

两性霉素B治疗获得性免疫缺陷综合征合并深部真菌感染疗效及安全性的回顾性分析

目的 回顾性分析两性霉素B治疗AIDS合并深部真菌感染的疗效及安全性。方法 收集2019年1月1日至2023年5月31日在首都医科大学附属北京地坛医院接受两性霉素B治疗的AIDS合并深部真菌感染患者资料,对其用药期间的疗效及安全性指标进行监测。结果 共纳入患者25例。总有效率为84.0%,症状好转率为68.0%,22例发生不良反应,12例发生严重不良反应,不良反应类型以低钾血症、骨髓抑制、肾功能损伤和肝功能异常为主。结论 两性霉素B具有较高的临床疗效,但不良反应发生率高,临床使用时应密切监护。     

卵巢囊肿蒂扭转80例手术治疗的临床分析

目的：对采用手术治疗的方法治疗卵巢囊肿蒂扭转的临床效果进行比较分析。方法：选取本院2005年9月～2010年9月收治的160例卵巢囊肿蒂扭转的患者,随机分为观察组A（保守治疗）和观察组B（手术治疗）,各80例,观察对比两组治疗效果、手术并发症及不良反应发生率,进行统计学分析。结果：观察组A痊愈16例,显效15例,有效25例,无效24例,总有效率为38.75%;观察组B痊愈26例,显效28例,有效18例,无效8例,总有效率为67.50%,两组患者疗效及并发症对比差异有统计学意义（P〈0.05）。结论：应用手术治疗卵巢囊肿蒂扭转的临床效果显著,明显优于传统保守治疗,是此疾病的首选治疗方法,值得在临床上合理推广。     

阿立哌唑治疗精神分裂症的不良反应和疗效分析

目的探讨第二代抗精神病药物阿立哌唑在治疗精神分裂症中的不良反应与疗效。方法对60例住院的精神分裂症患者进行观察,给予阿立哌唑治疗4、8、12周,记录不良反应与疗效。于治疗前及治疗后4、8、12周周末采用副反应量表（TESS）及简明精神病评定量表（BPRS）对不良反应及临床疗效分别进行3次评定。结果 60例中有19例发生不良反应,发生率为32%。第4周已有痊愈8例,显著进步10例,进步10例,无效32例,有效率30.00%,显效率16.67%;第8周有痊愈11例,显著进步19例,进步16例,无效14例,有效率50.00%,显效率26.67%;第12周有痊愈18例,显著进步20例,进步15例,无效7例,有效率63.33%,显效率25.00%。结论阿立哌唑在治疗精神分裂症中不良反应较小,具有较高的安全性,由于其对锥体外系及体重的影响较小,故可提高患者的治疗依从性。     

注射用两性霉素B治疗艾滋病/HIV感染合并深部真菌感染的不良反应及防护

目的:为临床合理应用注射用两性霉素B(AMB)治疗人类免疫缺陷病毒(HIV)感染或艾滋病(AIDS)合并深部真菌感染提供参考。方法:收集某院2010年1月至2012年2月期间住院治疗的3 202例HIV/AIDS患者的临床资料,分析其中使用AMB治疗深部真菌感染患者的不良反应(ADR)发生及防护。结果:HIV/AIDS合并深部真菌感染患者948例,感染率为29.61%;899例使用AMB,其中18例出现ADR,发生率为2.00%。AMB静脉滴注的ADR主要表现为发热、腹泻、瘙痒、肝功能异常及血液系统毒性。及时停药或减量,同时对症治疗,可有效地减少、减轻药物的ADR。结论:AMB虽ADR多见,但其疗效确切,是治疗HIV/AIDS合并深部真菌感染比较安全、有效、经济的选择。只要合理用药,严密监测用药后患者病情进展,尽早发现ADR,及时采取有效措施,并将心理护理贯穿治疗始终,就能保证患者治疗的顺利进行。     

Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients

Invasive fungal infections are associated with a poor outcome and their incidence is rising. Amphotericin B has for a long time been the gold standard for treatment of these infections, but the conventional formulation is associated with a high incidence of adverse events. Lipid formulations of amphotericin, developed to overcome these drawbacks, are now routinely used in clinical practice for the treatment of invasive fungal infections in immunocompromised patients. Amphotericin B lipid complex (ABLC) is prepared from amphotericin complexed to two phospholipids, a process that confers a number of important pharmacodynamic and pharmacokinetic properties compared with conventional amphotericin B. The results of retrospective observational studies and the analysis of databases, including the large Collaborative Exchange of Antifungal Research (CLEAR) database, have shown ABLC to be associated with response rates of up to about 80% in patients with confirmed fungal infections and around 60% in those treated empirically. Intranasal administration of ABLC for prophylaxis of invasive fungal infection in immunocompromised patients is safe and appears to be a promising treatment strategy for the future. ABLC is associated with a substantially lower incidence of nephrotoxicity than conventional amphotericin. Infusion-related reactions also occur less frequently than with conventional amphotericin and can be managed using premedication protocols. When direct and indirect costs are measured, ABLC appears to be less expensive than conventional amphotericin. The number of approved antifungal agents that are effective treatments for invasive fungal infections is increasing. However, lipid formulations of amphotericin, such as ABLC, are effective and well tolerated and remain the standard of care in the treatment of invasive fungal infections. Treatment strategies such as intranasal administration for prophylaxis and combination therapy with newer agents are future directions for these agents.     

Best practice guidelines for the management of adverse events associated with amphotericin B lipid complex

Importance of the field: Amphotericin B lipid complex is a widely used lipid-based formulation of amphotericin B, which has a broad spectrum of activity against a variety of fungal pathogens. It has also been shown to be significantly less nephrotoxic than conventional amphotericin B. However, infusional drug reactions, similar to those seen when using conventional amphotericin B, have been reported in a significant number of patients, so it is important that these are prevented or managed effectively, particularly in light of the changing epidemiology of systemic fungal infections.

Areas covered in this review: This article reviews effective strategies that can be used to reduce the risk of drug delivery reactions associated with amphotericin B lipid complex. Preserving renal function and managing spikes in serum creatinine levels are also discussed.

What the reader will gain: The aim of this paper is to provide healthcare professionals with clear guidance on the management of adverse events associated with amphotericin B lipid complex. Recommendations are based upon the published evidence and clinical experience from a number of different centres.

Take home message: Amphotericin B lipid complex represents a valuable therapeutic option in the treatment of fungal infections but improved strategies for the management of infusion-related adverse events are required.     

Lipid-based amphotericin B for the treatment of fungal infections

The frequency of life-threatening fungal infections has increased dramatically over the past few decades. For more than 30 years amphotericin B has been the standard treatment for systemic and deep-seated fungal infections, primarily because of its broad spectrum of activity. Its usefulness is limited by a relatively high frequency of significant adverse events including infusion-related reactions and nephrotoxicity. In an effort to overcome these side effects, a number of lipid-based formulations were developed, each with its own composition and pharmacokinetic behavior. The clinical significance of these differences is unknown. Available clinical data suggest the formulations have a reduced propensity for causing nephrotoxicity. However, considering limited efficacy data, they should be reserved as second-line therapy for patients who cannot tolerate or fail an adequate trial of conventional amphotericin B or cannot benefit from other antifungal agents.     

棘白菌素类抗真菌药物预防侵袭性念珠菌血症有效性与安全性的Meta分析

目的:系统评价棘白菌素类抗真菌药物预防侵袭性念珠菌血症的有效性及安全性,为临床治疗提供循证参考。方法:计算机检索PubMed、Embase、Medline、Cochrane图书馆、中国期刊全文数据库、中文科技期刊数据库、万方数据,检索时限为建库起至2019年7月,收集棘白菌素类药物(试验组)对比常规抗真菌药物(两性霉素B及三唑类抗真菌药,对照组)预防侵袭性念珠菌血症有效性和安全性的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取并采用Cochrane系统评价员手册5.0.2进行质量评价后,采用Rev Man 5.2统计软件对突破性侵袭性真菌感染率、真菌感染死亡率、全因死亡率及因不良反应停药的发生率进行Meta分析。结果:共纳入7项RCT,合计3 219例患者。Meta分析结果显示,试验组患者突破性侵袭性真菌感染发生率[OR=0.58,95%CI(0.40,0.85),P=0.004]、真菌感染死亡率[OR=0.68,95%CI(0.51,0.92),P=0.01]和因不良反应停药的发生率[OR=0.52,95%CI(0.40,0.67),P<0.001]均显著低于对照组,差异均有统计学意义;两组患者全因死亡率比较,差异无统计学意义[OR=0.84,95%CI(0.67,1.05),P=0.13]。结论:与两性霉素B及三唑类抗真菌药比较,棘白菌素类药物用于预防侵袭性念珠菌血症可降低突破性侵袭性真菌感染发生率、真菌感染死亡率和因不良反应停药的发生率。     

Voriconazole: in the treatment of invasive aspergillosis

Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged > or =12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for > or =7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for > or=14 days). At the investigators' discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (approximately 30% of patients) and skin rashes (6%). Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.     

Lipid-based formulations of amphotericin B

Amphotericin B remains the drug of choice for the treatment of invasive fungal infections and visceral leishmaniasis. However, both the dose-dependent nephrotoxicity and the low response rates (10-80%) associated with amphotericin B limit its clinical use. The first marketed formulation of amphotericin B with deoxycholate, Fungizone, remains the "gold standard" in spite of its renal toxicity. Several investigations have been made to reduce the nephrotoxicity of amphotericin B by formulation strategies. Lipid-based formulations of amphotericin B were found to reduce toxicity and to increase tolerance and therapeutic efficacy. Three lipid formulations are now available in most countries: liposomal amphotericin B (AmBisome), amphotericin B lipid complex and amphotericin B colloidal dispersion. Amphotericin B colloidal dispersion was less nephrotoxic, but immediate reactions to this formulation were as frequent and severe as those to amphotericin B. Amphotericin B lipid complex appeared to be as effective as amphotericin B, with improved general and renal tolerability. Several comparative studies have confirmed that AmBisome has similar or superior efficacy relative to amphotericin B in various fungal infections, in visceral leishmaniasis and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. A significant drawback to the newer, less toxic, commercial lipid-based formulations is their cost. There is a need to develop more affordable lipid-based formulations of amphotericin B.     

Echinocandins: A ray of hope in antifungal drug therapy

Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3)-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall.Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT) and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis.The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.     

Caspofungin for the treatment of fungal infections: a systematic review of randomized controlled trials

During the last decade, owing to the low effectiveness and high toxicity of older antifungals, new antifungal agents have been released to the market for the treatment of patients with fungal infections. Several randomized controlled trials (RCTs) have been designed to evaluate the effectiveness of caspofungin in comparison with other antifungal agents. This review was conducted to examine further the role of caspofungin in the treatment of patients with fungal, mainly Candida, infections. Two reviewers independently performed the literature search, study selection and data extraction from relevant RCTs. A total of six RCTs comparing caspofungin with amphotericin B (deoxycholate in four and liposomal in one RCT) or fluconazole (in one RCT), which studied a total of 1974 patients, were included in our review. Success of the applied treatment in the clinically evaluable patients was achieved in 496/943 (52.6%) of the caspofungin-treated patients and in 381/852 (44.7%) of the amphotericin B- and lipid amphotericin B-treated patients. Discontinuation due to drug toxicity was significantly less common in patients receiving caspofungin than amphotericin B (odds ratio (OR) 0.25, 95% confidence interval (CI) 0.07-0.85, random effects model). Development of nephrotoxicity, hypokalaemia and fever also occurred significantly less often with caspofungin than amphotericin B (OR 0.23, 95% CI 0.14-0.36, fixed effects model; OR 0.3, 95% CI 0.12-0.76, random effects model; and OR 0.26, 95% CI 0.08-0.79, random effects model, respectively). No difference in mortality was noted. Caspofungin was associated with better clinical outcomes (higher cure and fewer adverse effects) than amphotericin B in the treatment of patients with fungal infections.