Invasive pulmonary aspergillosis

In susceptible patients, invasive aspergillosis has a high incidence and a mortality of up to 80%. The diagnosis of this condition is difficult, especially in the early stages of the disease and, as a consequence, antifungal therapy, despite its expense and toxicity, is often initiated empirically. Until recently, there were very few effective antifungal agents for established invasive aspergillosis, but the introduction of two new drugs, voriconazole and caspofungin, has increased the treatment options. These newer antifungal therapies, combined with improved early diagnosis due to the introduction of newer microbiologic techniques, offer the hope that there will be a significant improvement in the substantial morbidity and mortality associated with invasive aspergillosis over the next 5 years.     

Impact of alternate definitions of fever resolution on the composite endpoint in clinical trials of empirical antifungal therapy for neutropenic patients with persistent fever: analysis of results from the Caspofungin Empirical Therapy Study

BACKGROUND: Sensitivity analyses were incorporated in a Phase III study of caspofungin vs. liposomal amphotericin B as empirical antifungal therapy for febrile neutropenic patients to determine the impact of varying definitions of fever resolution on response rates. METHODS: The primary analysis used a 5-part composite endpoint: resolution of any baseline invasive fungal infection, no breakthrough invasive fungal infection, survival, no premature discontinuation of study drug, and fever resolution for 48 h during the period of neutropenia. Pre-specified analyses used 3 other definitions for fever resolution: afebrile for 24 h during the period of neutropenia, afebrile at 7 days post therapy, and eliminating fever resolution altogether from the composite endpoint. Patients were stratified on entry by use of antifungal prophylaxis and risk of infection. Allogeneic hematopoietic stem cell transplants or relapsed acute leukemia defined high-risk patients. RESULTS: In the primary analysis, 41% of patients in each treatment group met the fever-resolution criteria. Low-risk patients had shorter durations of neutropenia but failed fever-resolution criteria more often than high-risk patients. In each exploratory analysis, response rates increased in both treatment groups compared to the primary analysis, particularly in low-risk patients. CONCLUSIONS: Response rates for the primary composite endpoint for both treatment groups in this study were driven by low rates of fever resolution. Requiring fever resolution during neutropenia in a composite endpoint can mask more clinically relevant outcomes.     

卡泊芬净联合万古霉素治疗肾移植术后肺部感染的疗效观察

目的 评价卡泊芬净联合万古霉素治疗肾移植术后肺部感染患者的疗效。方法 选取西安交通大学第一附属医院2018年8月-2019年10月收治的肾移植术后肺部感染患者122例为研究对象,按照随机数表法将患者分为对照组和观察组,每组各61例。对照组患者静脉滴注注射用盐酸去甲万古霉素,250 mg/次,采用0.9%氯化钠注射液250 mL溶解,滴注时间>1 h,12 h/次。用药3 d后,根据血药浓度谷峰值调整给药剂量。观察组患者在对照组的基础上静脉滴注注射用醋酸卡泊芬净,首次给药剂量为70 mg,使用200 mL葡萄糖溶液溶解,第2天开始以维持剂量为50 mg治疗,1次/d。两组疗程均为14 d。观察两组患者的临床疗效,比较两组治疗前后的肾功能指标、肺功能指标及血气指标水平。结果 治疗后,观察组治疗后总有效率为91.80%,显著高于对照组的77.05%,两组总有效率比较差异具有统计学意义（P<0.05）;治疗后,观察组细菌完全清除率为34.43%,显著高于对照组的14.75%,两组细菌完全清除率比较差异有统计学意义（P<0.05）。两组患者治疗后尿微量白蛋白/肌酐比值（ACR）、血肌酐（Scr）、尿β2-微球蛋白均显著升高（P<0.05）,组间比较观差异无统计学意义。两组患者治疗后肺功能指标第1秒用力呼气容积用力呼气容积（FEV₁）、第1秒用力呼气容积占预计值百分比（FEV₁% pred）和FEV₁/FVC均显著升高（P<0.05）,治疗后,观察组肺功能指标水平显著高于对照组,差异具有统计学意义（P<0.05）。治疗后,两组患者的动脉血氧饱和度（SaO₂）、动脉血氧分压（pO₂）和氧合指数（OI）均显著升高,动脉血二氧化碳分压（pCO₂）显著降低,同组治疗前后比较差异具有统计学意义（P<0.05）;治疗后,观察组患者的SaO₂、pO₂、OI显著高于对照组,pCO₂明显低于对照组（P<0.05）。结论 卡泊芬净联合万古霉素治疗肾移植术后肺部感染具有可靠的应用价值,能够有效抑制患者肺部感染,卡泊芬净与万古霉素联合应用起效迅速,但仍需根据患者实际情况合理选择用药。     

伏立康唑联合卡泊芬净治疗儿童白血病合并侵袭性真菌病疗效分析

目的:研究伏立康唑和卡泊芬净联合治疗儿童白血病化疗期间侵袭性真菌病(IFD)的临床疗效和安全性。方法:选取2015-2018年在我院接受抗侵袭性真菌感染治疗的41例白血病患儿,分为联合治疗组22例和伏立康唑组19例,其中联合治疗组患儿采用卡泊芬净联合伏立康唑治疗,伏立康唑组采用伏立康唑单独治疗,比较两组患儿用药后的治疗效果、感染死亡的风险因素和不良反应发生率。结果:联合治疗组与伏立康唑组临床有效率分别为77.3% 和36.9%,差异有统计学意义(P<0.05);联合治疗组死于感染相关因素的患儿少于伏立康唑组(P<0.05),治疗方式是IFD致死的风险因素(P<0.05);联合治疗组患儿出现肾功能和消化系统损伤的概率小于伏立康唑组(P<0.05)。结论:泊芬净和伏立康唑联合治疗儿童白血病合并侵袭性真菌感染的临床效果较好,可降低病死率和不良反应发生率。     

Trichosporon Asahii,Sepsis, and Secondary Hemophagocytic Lymphohistiocytosis in Children with Hematologic Malignancy

Trichosporon asahii (T. asahii) is an uncommon fungal pathogen rarely seen in patients with hematologic malignancies. Although appropriate therapy is started, infection with T. asahii usually leads to mortality. Here, we describe two patients developed severe T. asahii infection and secondary HLH. Despite rapid identification of T. asahii and negative blood cultures achieved by prompt initiation of treatment with voriconazole, fever and pancytopenia, persisted and both developed hepatosplenomegaly, and their clinical state worsened. Bone marrow aspiraton revealed hemophagocytosis. Elevated ferritin, triglyceride levels were seen. The first patient did not receive HLH directed therapy and died with multiple organ dysfunctions. Prompt diagnosis and treatment of secondary HLH led to rapid improvement in clinical and laboratory abnormalities in the second patient and kept her alive. We suggest that HLH may present as a secondary condition, accompanying a severe infection with T. asahii may, at least in part, contribute to high mortality rates in these cases.     

卡泊芬净在器官移植术后侵袭性真菌感染病人中的应用

目的对卡泊芬净治疗器官移植术后侵袭性真菌感染的疗效进行评价。方法采用病例对照研究方法,选择我院器官移植术后出现侵袭性真菌感染病人100例,分为3组。卡泊芬净组36例,氟康唑组36例,两性霉素B组28例,分别予卡泊芬净、氟康唑和两性霉素B治疗,观察抗真菌治疗疗效。结果卡泊芬净组、氟康唑组和两性霉素B组抗真菌治疗的有效率分别为76%、81%和67%,3组疗效无显著差异(P>0.05)。卡泊芬净组与氟康唑组、两性霉素B组用药过程中的不良反应发生率分别为6%、6%和14%。结论卡泊芬净对于器官移植术后病人侵袭性真菌感染有明显的治疗作用,疗效与两性霉素B和氟康唑相当。     

Caspofungin for invasive fungal infections: combination treatment with liposomal amphotericin B in children undergoing hemopoietic stem cell transplantation

Abstract:  Invasive fungal infections often prove difficult to eradicate especially in the stem cell transplant setting. Amphotericin has been the mainstay of treatment for years but has significant toxicity. Newer antifungal agents, such as caspofungin, have shown promising results in adults, particularly when used in combination with amphotericin as both drugs differ in their mode of action. However, there are few data from children and no previous published information about the use of Caspofungin after paediatric stem cell transplantation. We report our experience in children with proven invasive fungal infections after stem cell transplantation. This combination was non-toxic, and two of three patients survived their infections.     

New systemic antifungal drugs: mechanisms of action,drug interactions and side effects

New antifungal agents are needed to match the currently increasing rate of systemic fungal infections and the development of resistant fungal strains. This appears possible by the introduction of second generation azole antifungals which potently inhibit ergosterol synthesis, but also by a partial synthetic echinocandin analogue which acts by the suppression of the enzyme glucan synthase. Voriconazole and caspofungin have been approved for the treatment of invasive aspergillosis. Both drugs are well tolerated if contraindications and--with voriconazole--also possible drug interactions are respected. Possibly these drugs are also suitable for other severe fungal infections including systemic and oropharyngeal candidosis in the immunocompromised host.     

卡泊芬净在移植患者中应用的安全性评价

 目的拟对卡泊芬净在器官移植术后患者深部真菌感染治疗过程中的安全性进行评价。方法采用病例对照研究方法,以应用氟康唑或两性霉素B治疗的患者为对照组,数据采用SPSS14.0处理。结果试验组和对照2组患者治疗前后ALT,对照2组患者治疗前后血BUN治疗前后的差异有统计学意义(P<0.05)。试验组和对照2组用药后血浆电解质水平有所变化(P<0.05)。对照1组用药前后他克莫司血药浓度有统计学意义。3组不良反应发生率分别为5.6%,5.6%和14.3%。结论卡泊芬净用于治疗移植术后患者深部真菌感染有较好的安全性。