两性霉素B治疗侵袭性真菌感染回顾性研究

目的评估两性霉素B（AmB）治疗侵袭性真菌感染的安全性、有效性及经济性。方法回顾性分析AmB优化生产工艺前后两年时间内侵袭性真菌感染住院治疗患者113例临床资料。结果临床有效率为76％以上。不良反应中,低钾血症发生率为33．6％、肌酐（Cr）、尿素氮（BUN）一过性升高发生率分别为29．0％和27．4％,发热等即刻反应总发生率为15．0％;未发现归因于AmB导致的死亡和不可逆的肾功能损害。工艺改进后,过敏等即刻反应明显下降（发生率由28．0％降至7．2％）。以感染性心内膜炎、骨髓炎、隐球菌脑膜炎等疾病为例,按12周标准疗程和常规剂量静脉注射计算费用,AmB的治疗费用约为4600元,氟康唑（进口）为38000元,伊曲康唑为99100元,AmB脂质体为190000元,伏立康唑为250000元,醋酸卡泊芬净为270000元。结论AmB仍是目前抗真菌药物中疗效最佳者;生产工艺改进后发热等即刻不良反应的发生率显著减少;绝大部分患者可以完成治疗,获得治愈;其明显的药效-经济学优势在侵袭性真菌感染特别是需长期治疗的疾病中具有不可替代的作用和地位。     

两性霉素B脂质体治疗侵袭性真菌感染临床分析

目的 观察两性霉素B脂质体(amphotericin B liposome,L-AmB)对外科ICU侵袭性真菌感染(invasive fungal innfections,IFI)的临床疗效及安全性.方法 13例外科ICU IFI患者使用L-AmB 1 nag/(kg·d)的剂量,观察治疗期间的临床疗效及不良反应.结果 13例患者中痊愈7例,显效3例,进步2例,无效1例,总有效率76.9%,不良反应较小.结论 小剂量的L-AmB 1 mg/(kg·d)应用于外科ICU IFI患者疗效确切,不良反应小,值得临床推广应用.     

米卡芬净治疗免疫功能低下患者侵袭性真菌感染的疗效及安全性分析

侵袭性真菌感染(IFI)是引起免疫功能缺陷的患者死亡的主要原因之一,寻找高效低毒的抗真菌药物对于提高免疫功能缺陷患者的长期存活十分重要。米卡芬净(mica-fungin)是一种1,3-β-D-葡聚糖合成酶抑制剂,其抗菌谱广,在体内、外对曲霉菌、念珠菌均有抗菌活性[1]。我们对7例IFI的患     

两性霉素B脂质体治疗恶性血液病侵袭性真菌感染的临床观察

目的:探讨两性霉素B治疗恶性血液病并发侵袭性真菌感染的有效性及安全性.方法:选择58例经临床资料和(或)生物学证实恶性血液病并发侵袭性真菌感染的患者,均使用两性霉素B脂质体治疗,起始剂量为0.1 mg· kg-1·d1,维持剂量为0.5～1.o mg· kg1·d1;静脉滴注时间＞4 h；用药时间12～60 d,中位数...     

两性霉素B对老年白血病化疗后肺部侵袭性真菌感染的疗效研究

目的探讨两性霉素B对老年白血病化疗后肺部侵袭性真菌感染患者的临床治疗效果。方法选取我院自2014年1月至2015年7月收治的65例白血病化疗后发生肺部侵袭性真菌感染的患者作为研究对象,随机的分为研究组35例,对照组各30例,研究组患者给与两性霉素B进行治疗,对照组患者给与米卡芬净进行治疗,观察两组患者的临床疗效和不良反应发生情况。结果治疗后研究组临床总有效率为85.71%(30/35),患者G试验转阴率为89.28%(25/28),对照组为56.67%(17/30),G试验转阴率为76.00%(19/25),组间比较差异显著(P0.05),具有统计学意义;两组患者不良反应发生率比较差异不显著(P0.05)。结论可选择两性霉素B对老年白血病化疗后肺部侵袭性真菌感染的患者进行治疗,其效果显著,经济性较高,可推广使用。     

23例血液病患者侵袭性真菌感染临床分析

目的:分析23例血液病患者并发侵袭性真菌感染(IFI)的宿主因素、临床特点、抗真菌治疗及疗效。方法:回顾性分析23例侵袭性真菌感染的临床资料。结果:宿主免疫功能低下是导致IFI的重要因素之一。IFI中肺部感染最多见,占82.6%(19/23例)。发热、呼吸困难、低氧血症、肺部影像学变化是IFI最常见的临床特征,也是临床观察及判断疗效的重要指标。所有IFI患者发热占87.0%(20/23例),19例肺部真菌感染病例几乎均伴有发热、呼吸困难,并发低氧血症占84.2%(16/19例)。肺部真菌感染患者均出现肺部影像学改变,其中典型的光晕征或新月征占63.2%(12/19例)。上述临床特点不具备特征性,尽快获得病原学证据比较困难。目前综合上述临床特点、按照中国IFI诊断指南是临床诊断IFI的主要方法。本研究中抗真菌治疗总有效率(痊愈加显效)66.7%,抗真菌治疗药物安全性良好。结论:免疫功能状态与IFI发生及治疗疗效相关,早期诊断IFI困难。对真菌感染进行临床分层诊治是血液病发生IFI的重要诊治模式。     

两性霉素B脂质体与伏立康唑治疗侵袭性肺曲霉菌病临床对比观察

目的对比观察伏立康唑与两性霉素B脂质体治疗侵袭性肺曲霉菌病的效果和不良反应。方法研究对象为62例疑似或确诊侵袭性肺曲霉菌病患者,根据治疗药物不同分为伏立康唑组28例、两性霉素B脂质体组34例。伏立康唑组首日给予负荷剂量伏立康唑,6 mg/kg、2次/d;此后给予维持剂量,即3 mg/kg、2次/d。两性霉素B脂质体组给予两性霉素B脂质体治疗,起始剂量及维持剂量均为0.3 mg/kg、1次/d。有明确病原学证据时伏立康唑组剂量增至4 mg/kg、2次/d,两性霉素B组剂量增至0.6 mg/kg、1次/d。比较两组治疗效果及不良反应。结果伏立康唑组及两性霉素B组治愈率分别为28.6%、44.1%,P<0.05;总有效率分别为42.8%、58.8%,P<0.05。伏立康唑组用药期间未出现肾功能损害,两性霉素B脂质体组出现肾功能损害3例,P<0.05。结论两性霉素B脂质体治疗侵袭性肺曲霉菌病的有效率及治愈率均高于伏立康唑,但肾功能损害发生率高于伏立康唑。     

两性霉素B治疗侵袭性肺部真菌感染的安全性分析

目的探讨两性霉素B治疗侵袭性肺部真菌感染的疗效及其安全性。方法分析我院应用两性霉素B治疗确诊或拟诊为侵袭性肺部真菌感染者的临床资料。结果两性霉素B治疗34例侵袭性肺部真菌感染,疗效满意,有效率91.2%。不良反应发生率47%,畏寒、寒颤5.8%;消化道反应(恶心、呕吐、胸闷)23.5%;肾功能受损2.9%;肝损害,5.8%;低钾血症23.5%。结论两性霉素B治疗肺部侵袭性真菌感染,疗效高,是有效治疗曲霉菌和非白色念珠菌感染的首选之一。     

两性霉素B雾化吸入治疗肺真菌感染的临床观察

临床上常见肺部真菌感染患者多为免疫功能低下、慢性肺疾病、糖尿病等患者,感染相关死亡率高。两性霉素B是多烯大环内酯类抗生素,是目前公认治疗深部真菌感染的药物之一,但由于其不良反应大限制了其临床应用。为了探讨两性霉素B雾化吸入途径治疗肺真菌感染的疗效及安全性,我们选择了2006年9月-2011年3月在我院住院的50例肺真菌感染患者的治疗效果进行比较。现将结果报道如下。     

151例侵袭性真菌感染的临床特点分析

目的探讨侵袭性真菌感染（IFI）的临床特点,高危感染因素及对不同药物的治疗反应。方法采取回顾性研究探讨151例确诊为侵袭性真菌感染患者的临床特点,高危易感因素,病原学分布情况及其对不同药物治疗的反应。评估不同药物治疗IFI的临床疗效和不良反应。对相应结果应用SPSS11．0软件包进行统计分析。结果151例IFI患者中感染前使用广谱抗生素者占49．02％,粒细胞缺乏者占45．10％。感染部位以单纯呼吸道感染为主（74．17％）。确诊和临床诊断的43例患者中共分离出致病真菌43例,其中自假丝酵母菌所占比例最大（占44．19％）。伏立康唑组的总有效率与两性霉素B组比较无显著性差异（P〉0．05）,但其不良反应发生率低于两性霉素B组（11．62％比63．08％,P〈0．05）。结论本组侵袭性真菌感染以念珠菌属感染为主,广谱抗生素的应用及粒细胞缺乏是侵袭性真菌感染的高危易感因素。伏立康唑的临床疗效与两性霉素B相当,但不良反应的发生率较两性霉素B少。     

Liposomal Amphotericin B (AmBisome) in the Treatment of Neonatal Candidiasis in Very Low Birth Weight Infants

Summary AmBisone (2.5–7 mg/kg/day as a continuous 1 h infusion) was evaluated prospectively from September 1994 to January 1998 in 24 very low birth weight infants (mean birth weight 847±244 g, mean gestational age 26 weeks) with systemic candidiasis. Mean age at onset of candidemia was 17 days. One patient had two episodes of candidiasis. Thirteen infants failed previous antifungal therapy with amphotericin B (with or without 5-flucytosine). Candida spp. were isolated from the blood in all 25 episodes and from skin abscesses and urine in four infants each, respectively. There were 13 isolates of Candida albicans, ten of Candida parapsilosis, two of Candida tropicalis and one of Candida glabrata. One infant had a mixed infection with C. albicans and C. parapsilosis. The mean duration of therapy was 21 days; the cumulative AmBisome dose was 94 mg/kg. Fungal eradication was achieved in 92% of the episodes; mean duration of AmBisome therapy until achieving eradication was 9 days. Twenty (83%) infants were considered clinically cured at the end of treatment. No major adverse effects were recorded; one infant developed increased bilirubin and hepatic transaminases levels during therapy. Four (17%) infants died; in two of them (8%) the cause of death was directly attributed to systemic candidiasis. Conclusion: AmBisome represents an effective, safe and convenient antifungal agent in the therapy of systemic fungal infections in very low birth weight infants. Received: March 21, 1999 · Revision accepted: March 3, 2000     

两性霉素B治疗恶性血液肿瘤合并真菌感染40例临床分析

目的：观察静脉用两性霉素B对血液系统恶性肿瘤病人真菌感染的临床疗效及安全性。方法：40例恶性血液病患者（男27例,女13例,中数年龄35．5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5－85d,中数21d.结果：两性霉素B临床总有效率为52．5％,真菌清除率为56．2％,不良反应发生率中寒战,发热2．5％,低血钾12．5％,肝肾功能损害各为15．0％。结论：两性霉素B因其抗菌谱较广,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。     

Fungal infections in lung transplantation

Lung transplant is a potential life-saving procedure for chronic lung diseases. Lung transplant recipients (LTRs) are at the greatest risk for invasive fungal infections (IFIs) among solid organ transplant (SOT) recipients because the allograft is directly exposed to fungi in the environment, airway and lung host defenses are impaired, and immunosuppressive regimens are particularly intense. IFIs occur within a year of transplant in 3–19% of LTRs, and they are associated with high mortality, prolonged hospital stays, and excess healthcare costs. The most common causes of post-LT IFIs are Aspergillus and Candida spp.; less common pathogens are Mucorales, other non-Aspergillus moulds, Cryptococcus neoformans, Pneumocystis jirovecii, and endemic mycoses. The majority of IFIs occur in the first year following transplant, although later onset is observed with prolonged antifungal prophylaxis. The most common manifestations of invasive mould infections (IMIs) include tracheobronchial (particularly at anastomotic sites), pulmonary and disseminated infections. The mortality rate of tracheobronchitis is typically low, but local complications such as bronchomalacia, stenosis and dehiscence may occur. Mortality rates associated with lung and disseminated infections can exceed 40% and 80%, respectively. IMI risk factors include mould colonization, single lung transplant and augmented immunosuppression. Candidiasis is less common than mould infections, and manifests as bloodstream or other non-pulmonary invasive candidiasis; tracheobronchial infections are encountered uncommonly. Risk factors for and outcomes of candidiasis are similar to those of non lung transplant recipients. There is evidence that IFIs and fungal colonization are risk factors for allograft failure due to chronic rejection. Mould-active azoles are frontline agents for treatment of IMIs, with local debridement as needed for tracheobronchial disease. Echinocandins and azoles are treatments for invasive candidiasis, in keeping with guidelines in other patient populations. Antifungal prophylaxis is commonly administered, but benefits and optimal regimens are not defined. Universal mould-active azole prophylaxis is used most often. Other approaches include targeted prophylaxis of high-risk LTRs or pre-emptive therapy based on culture or galactomannan (GM) (or other biomarker) results. Prophylaxis trials are needed, but difficult to perform due to heterogeneity in local epidemiology of IFIs and standard LT practices. The key to devising rational strategies for preventing IFIs is to understand local epidemiology in context of institutional clinical practices.     

Diagnostic Usefulness of a T-cell-based Assay for Extrapulmonary Tuberculosis in Immunocompromised Patients

Background

The low reactivity of the tuberculin skin test limits its clinical use in immunocompromised patients with extrapulmonary tuberculosis. A recently developed T-cell-based assay for diagnosing tuberculosis infection gave promising results. However, there were few data on the usefulness of this assay for diagnosing extrapulmonary tuberculosis in immunocompromised patients.

Methods

All adult patients with suspected extrapulmonary tuberculosis were prospectively enrolled at 2 university-affiliated hospitals over an 18-month period. In addition to the conventional tests for diagnosing extrapulmonary tuberculosis, enzyme-linked immunospot (ELISPOT) assay for the interferon-γ-producing T-cell response to early secretory antigenic target-6 and culture filtrate protein-10 was performed. The final diagnoses in patients with suspected extrapulmonary tuberculosis were classified by clinical category.

Results

There were 179 patients with suspected extrapulmonary tuberculosis enrolled: 59 (33%) were classified as immunocompromised. Of the 179 patients, 75 (42%) were classified as extrapulmonary tuberculosis, including 56 confirmed tuberculosis plus 19 probable tuberculosis, and 97 (54%) were classified as not tuberculosis. The remaining 7 (4%) had possible tuberculosis and were excluded from the final analysis. The tuberculin skin test (induration size ≥10 mm) was less sensitive in immunocompromised patients (38%; 95% confidence interval [CI], 19%-59%) than in immunocompetent patients (69%; 95% CI, 54%-81%, P = .01). In contrast, the ELISPOT assay retained a high sensitivity: (88%; 95% CI, 68%-97%) in immunocompromised patients compared with 96% (95% CI, 87%-100%) in immunocompetent patients (P = .32).

Conclusion

The immunosuppressive condition does not affect the diagnostic sensitivity of the ELISPOT assay for extrapulmonary tuberculosis.     

Granulocyte Colony Stimulating Factor Increases the Efficacy of Conventional Amphotericin in the Treatment of Presumed Deep-Seated Fungal Infection in Neutropenic Patients following Intensive Chemotherapy or Bone Marrow Transplantation for Haematological Malignancies

A prospective, comparative study of empiric amphotericin B with, or without, granulocyte colony stimulating factor was carried out to assess whether the addition of granulocyte colony stimulating factor to empiric amphotericin B improves the clinical response in neutropenic patients with suspected or proven fungal infection. Fifty nine neutropenic adults with haematological malignancy and antibiotic-refractory fever or clinical evidence of deep-seated fungal infection were studied. Patients received intravenous colloidal amphotericin B (1 milligram per kilogram body weight) with or without subcutaneous granulocyte colony stimulating factor (three to five micrograms per kilogram body weight). Thirty patients received amphotericin alone and 29 amphotericin plus granulocyte colony stimulating factor. Nearly twice as many patients responded to amphotericin B with concomitant administration of granulocyte colony stimulating factor (62%) as responded to amphotericin alone (33%; difference in proportions 0.29,95%CI 0.03–0.54). Clinical response in patients receiving granulocyte colony stimulating factor coincided with neutrophil recovery in most cases. Addition of granulocyte colony stimulating factor to empiric amphotericin B significantly reduced the number of patients requiring salvage therapy with lipid-associated or liposomal formulations of amphotericin B addition of granulocyte colony stimulating factor to empiric intravenous amphotericin B improves the response rate and thereby reduces the number of patients requiring salvage therapy with liposomal or lipid-associated preparations of amphotericin B.