原位肝移植术后并发曲霉菌感染的诊断和治疗

目的 探讨原位肝移植术后并发曲霉菌感染的诊断和治疗措施. 方法对2000年1月至2006年12月中山大学附属第一医院施行的776例同种原位肝移植患者的临床资料进行回顾性分析,总结原位肝移植术后发生曲霉菌感染的诊治经过.结果 本组患者发生曲霉菌感染13例,感染发生率为1.68%(13/776);其中肺部感染7例,肝脏感染2例,颅内感染1例,多器官感染3例.两性霉素B脂质体是治疗肝移植术后曲霉菌感染的主要药物,对早期病例疗效满意.因曲霉菌感染死亡7例,病死率为53.8%(7/13).结论 防治肝移植术后曲霉菌感染的关键是做好早期诊断,及时治疗.抗真菌治疗应该清除病灶、调整免疫抑制剂及选用敏感抗真菌药物;抗真菌药物的使用应该早期、足量、全程用药.     

原位肝移植术后真菌感染的诊治

目的 探讨原位肝移植术后真菌感染的诊断和治疗。方法 58例肝移植患者术后怀疑真菌感染时，行体液（痰、血、尿、胆汁、引流液等）或导管真菌培养，结合胸腹部CT影像学检查、活组织检查及诊断性治疗结果综合判断，一旦诊断确定，即给予氟康唑治疗，无效者改用伊曲康唑和两性霉素B，同时调整免疫抑制治疗方案。结果 58例患者中，16例术后并发真菌感染21例次（5例患者发生两次以上、不同部位或不同菌株的感染），感染发生率为27．6％（16／58），感染发生在术后4～38d，感染好发部位依次为肺（28．6％）、肠道（19．0％）、泌尿系统（14．3％）、腹腔（14．3％）、切口（9．5％）、血液（4．8％）、胆管（4．8％）及肝脏（4．8％）。在21例次真菌感染中，念珠菌感染占85．7％，曲霉菌感染占14．3％。氟康唑治疗有效者占66．7％，伊曲康唑治疗有效者占14．3％，两性霉素B治疗有效者占14．3％，1例（4．7％）各种抗真菌药物治疗均无效，治疗总有效率为95．2％。结论 肝移植术后真菌感染的发生率较高，依据影像学检查、病原学检查及活组织检查综合判断真菌感染，及时选用氟康唑、伊曲康唑及两性霉素B治疗。     

肾移植术后侵袭性肺曲霉菌病的诊治

目的 探讨肾移植受者侵袭性肺曲霉菌感染的诊断与治疗. 方法肾移植术后侵袭性肺曲霉菌病患者10例.男7例,女3例.年龄28～56岁,平均43岁.感染发病时间为术后平均59 d.患者低氧血症和呼吸困难严重.10例均行纤维支气管镜、肺部CT检查和血清半乳甘露聚糖(GM)抗原检测.其中纤维支气管镜取分泌物培养阳性3例,肺部CT检查有明显影像学特征6例,血清GM抗原检测阳性5例.应用伊曲康唑和两性霉素B脂质体治疗,剂量为伊曲康唑第1天400mg静脉滴注,第2天起200 mg静脉滴注,共14 d;两性霉素B脂质体治疗剂量为50 mg加入5%葡萄糖注射液500 ml中慢速静脉滴注约8 h,共14～28 d.结果 3例应用伊曲康唑治愈,5例应用两性霉素B脂质体治愈,2例死亡.结论 侵袭性肺曲霉菌感染是肾移植术后肺部感染的严重并发症,早期诊断与正确治疗可降低病死率.     

原位肝移植术后48例次真菌感染的诊治体会

目的探讨原位肝移植术后真菌感染的诊断及治疗方法。方法回顾性分析147例肝移植受体术后发生真菌感染的诊治情况。结果147例患者中，29例发现真菌感染48例次，感染率为19．73％（29／147）。感染好发的部位依次为肺（33．34％，16／48），肠道（22．92％，11／48），泌尿系统（20．83％，10／48）。其中白色念珠菌感染占52．08％，光滑念珠菌感染占22．92％，热带念珠菌感染占12．50％，曲霉菌感染占8．34％，毛霉菌感染占4．17％。氟康唑治疗有效者占41．38％，伊曲康唑治疗有效者占27．59％，科赛斯治疗有效者13．79％，24例感染患者治愈，总有效率为82．76％。5例死亡，病死率17．24％。结论肝移植术后真菌感染的发生率较高，依据影像学检查和病原学检查等可早期诊断真菌感染，及时选用氟康唑、伊曲康唑及科赛斯等早期治疗是治愈真菌感染的关键。     

肝移植术后肺部真菌感染的诊断和治疗

目的探讨肝移植术后肺部真菌感染的早期诊断及治疗方法。方法回顾分析20例肝移植术后肺部真菌感染患者的临床资料，分析其原发病、免疫状态、感染真菌的种类及抗真菌药物的应用。结果20例患者念珠菌感染17例，死亡2例，曲霉菌感染3例，死亡2例。氟康唑、伊曲康唑、两性霉素B治疗有效率70％，伏立康唑、卡泊芬净治疗有效率100％。结论肝移植术后真菌感染高发，以危重患者为主要目标人群，发生早，病情重。诊断分三级，达到临床诊断即应及早治疗。治疗以伏立康唑为首选，严重感染者联合应用卡泊芬净效果良好。     

肝移植术后侵袭性曲菌病的防治

目的探讨原位肝移植术后侵袭性曲菌病的防治。方法回顾性分析2000年1月至2005年1月完成的576例原位肝移植的临床资料,总结术后侵袭性曲菌病的预防和治疗经验。结果9例患者术后并发侵袭性曲菌病,发病率为1.74%(9/576),首发感染部位为肺部8例,中枢神经系统感染1例。6例患者停用免疫抑制治疗,3例患者将他克莫司(FK506)或CsA降低到最低有效血药浓度。6例患者选用两性霉素B脂质体(其中1例先试用氟康唑)、3例首选伊曲康唑进行治疗。5例肺部感染患者痊愈,2例因肺部感染无法控制死亡,2例因并发多器官曲霉菌感染死亡。结论早发现并及时调整免疫抑制治疗方案,早期、足量和足程使用抗真菌药物,积极行手术治疗是降低肝移植术后侵袭性曲菌病发病率和病死率的根本措施。     

肝移植术后手术部位曲霉菌及毛霉菌感染临床分析

目的 探讨原位肝移植术后手术部位曲毛霉菌感染的防治.方法 回顾性分析我院肝胆外科2例感染曲毛霉菌患者的临床资料,对其症状、诊断及治疗进行总结.结果 例1患者术后移植物动脉感染曲霉菌及毛霉菌,导致血管突发破裂出血,终因多器官功能衰竭死亡.另1例患者术后出现手术切口深部毛霉菌感染并合并肺曲霉菌感染,给予强效抗真菌支持治疗后无明显好转,最终死于全身严重感染及呼吸功能衰竭.结论 肝移植术后以手术部位为首发临床表现的曲毛霉菌混合感染临床表现隐匿,病情进展快,预后凶险.     

肾移植术后侵袭性肺曲霉感染15例临床诊治

目的：探讨肾移植受者术后侵袭性肺曲霉（ IPA）感染的诊治。方法回顾性分析济南军区总医院泌尿外科2008年7月至2013年5月肾移植术后15例IPA感染受者的临床资料。结果15例受者均为首次肾移植,均为肾移植术后半年内发生IPA感染,最早于术后16 d发现。经半乳甘露聚糖试验（ GM试验）检出IPA 9例,肺部CT检查检出4例,血培养检出3例,痰培养检出5例。9例合并CMV或细菌感染,2例合并假丝酵母菌属感染,4例为单纯性IPA感染。13例IPA感染受者给予伏立康唑注射液治疗（3例为确诊病例,10例为临床诊断病例）,其中2例合并或序贯给予米卡芬净;另2例临床诊断病例给予伊曲康唑注射液治疗。共有9例受者治愈,6例死亡。结论 GM试验、肺部CT检查等对肾移植术后IPA感染具有一定的诊断价值,结合临床表现,能够较早诊断IPA感染,有助于及时进行早期治疗,提高患者生存率。     

肺移植术后曲霉菌感染(附4例报告和文献复习)

目的探讨肺移植术后曲霉菌感染的预防、监测和治疗方法。方法2003年1月至2004年9月，6例重度肺气肿病人成功实行同种异体单肺移植术，其中4例术后痰培养发现曲霉菌。结果2例临床上无肺部感染症状，口服伊曲康唑治疗近2个月。1例术后1个月纤维支气管镜提示支气管吻合口局部侧壁软化、狭窄，被坏死组织覆盖，活检找到霉菌，置入镍钛网状支架后症状改善。另1例术后并发自体肺严重曲霉菌浸润性肺部感染，咳出桔红色痰，量最多达180ml／d。X线胸片提示有空洞表现，经伊曲康唑静脉注射和应用两性霉素B雾化吸入治疗6周后，症状消失、X线胸片空洞关闭而治愈。结论应用伊曲康唑和两性霉素B雾化吸入，对肺移植术后早期曲霉菌感染的预防和治疗都是有效的。     

原位肝移植术后侵袭性曲菌病的诊断和治疗

目的探讨原位肝移植术后侵袭性曲菌病的诊治。方法回顾性分析2000年1月至2005年1月完成的576例原位肝移植的临床资料,总结术后侵袭性曲菌病的防治经验。结果9例患者术后并发侵袭性曲菌病,疾病发生率为1．74％（9／576）,首发感染部位为肺部8例,中枢神经系统感染1例,发病时间在术后10d至2个月,术后持续或间断的低热可以是发病早期的主要症状。痰或其他分泌物的真菌镜检和培养是确诊的主要依据。二性霉素B脂质体是治疗的首选用药,对早期病例疗效满意,5例肺部感染患者痊愈,2例因肺部感染无法控制死亡,2例因并发多器官侵袭死亡。结论肝移植术后侵袭性曲菌病具有早期临床表现不典型和易于播散的特点,合理调整免疫抑制治疗方案及早期、足量和足程的抗真菌药物的使用是取得良好疗效的关键。     

Native lung pneumonectomy for invasive pulmonary aspergillosis following lung transplantation: a case report.

Pulmonary aspergillosis occurs most commonly as a consequence of immunosuppression in recipients of pulmonary transplantation and is associated with a high mortality. It affects the native lung more commonly than the transplanted lung in single lung transplant patients. Infection often progresses despite aggressive medical therapy. The cornerstone of treatment of acute, semi-invasive, and invasive pulmonary aspergillosis (IPA) is medical, with intravenous amphotericin B, and oral itraconazole either as isolated or combined therapy. While newer, and more expensive liposomal forms of amphotericin B have been used to enhance tissue penetration and minimize renal toxicity, an appreciable improvement in clinical outcome has not been reported. The role of surgery in localized pulmonary aspergillus infection is well recognized, but remains undefined in immunosuppressed patients. We report a case where a pneumonectomy was performed for progressive, refractory angioinvasive aspergillosis in a lung transplant recipient whose disease progressed despite conventional antifungal therapy.     

Pulmonary Aspergillosis in Solid Organ Transplant Patients: A Report From Iran

Background

Aspergillosis is one of the most important opportunistic infections after organ transplantation. Early diagnosis and initiation of appropriate antifungal therapy are key factors for better prognosis.

Methods

We reviewed the medical records of patients with solid organ transplantation with evidence of Aspergillus infections from December 2001 to January 2008, evaluating patient demographics, time of onset after transplantation, risk factors, radiologic appearance, diagnostic criteria, antifungal therapy, and outcome.

Results

We observed aspergillosis in 8 lung, 3 kidney, and 1 heart recipient, with overall mean age of 40.6 years. Seven cases of Aspergillus tracheobronchitis were diagnosed in lung transplant recipients, all of them in the first 6 months after transplantation. All patients responded to antifungal therapy and bronchoscopic debridement. We observed 5 cases of invasive pulmonary aspergillosis. Three patients survived in response to antifungal treatment. The two patients who died were treated with a combination of itraconazole and amphotericin B, whereas all cured patients had been treated with voriconazole alone or in combination with caspofungin.

Conclusion

It seems that the prognosis of aspergillosis in solid organ recipients is improving with new treatment regimens, particularly if they are used in early stages of infection.     

Risk factors for invasive aspergillosis in liver transplant recipients

Aspergillosis is a potential, severe, and usually early complication of liver transplantation. New promising strategies, such as detecting Aspergillus antigenemia, have been used for the diagnosis of aspergillosis in immunosuppressed patients, but the impact in solid organ transplantation is not well known. A case-control study in 260 adults who underwent liver transplantation from January 1994 to June 2000 was performed. A case was defined as any liver transplant recipient with a proven or probable diagnosis of invasive aspergillosis. Controls were defined as a liver transplant recipient without aspergillosis infection with a survival longer than two months after transplantation. Clinical and analytical variables, including Aspergillus antigenemia, were compared. A special analysis was performed in patients in whom late aspergillosis developed (after day 100 posttransplantation). Among 260 patients, invasive aspergillosis developed in 15 (5.6%). Median time from transplantation to aspergillosis in 13 patients with sufficient data for analysis was 126 days (range, 22 to 1117). Seven (54%) developed the infection after day 100 posttransplantation. Thirty-eight patients were used as controls. Antigenemia was available in nine of 13 cases and in 33 of 38 controls. By multivariate analysis, retransplantation (OR, 29.9 [95% CI, 2.1 to 425.1]), dialysis requirements after transplantation (OR, 24.5 [95% CI, 1.25 to 354]), and the presence of Aspergillus antigenemia in serum at any time point after transplantation (OR, 50.0 [95% CI, 3.56 to 650]) were independently associated to aspergillosis. In the subgroup of patients that developed late aspergillosis, cytomegalovirus infection (OR, 6.7 [95% CI, 1.0 to 42.5]) was the only independent factor associated. Hepatic and renal dysfunction predispose to Aspergillus infection in liver transplant recipients. Cytomegalovirus infection and increased immunosuppression favor invasive aspergillosis during the late posttransplantation period. Aspergillus antigenemia seems to be a good predictor of invasive aspergillosis. (Liver Transpl 2002;8:1065-1070.)     

Efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients with invasive fungal infections

Background: Fungal infections following solid-organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients.
Methods: Three open-label, second-line treatment studies evaluated ABLC as a treatment for severe, life-threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre-existing renal disease.
Results: The 79 solid-organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n=39); candidiasis (n=20); zygomycosis (n=8); cryptococcosis and histoplasmosis (n=3 each); and blastomycosis, cladosporiosis, fusariosis, Bipolaris hawaiiensis , Dactylaria gallopava , and an unspecified fungal infection (n=1 each). The median duration of ABLC therapy was 28 d (1–178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty-six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n=37) or improved (n=27) serum creatinine at the end of treatment.
Conclusions: ABLC is safe and effective treatment for fungal infections in solid-organ transplant recipients. Its renal-sparing properties are particularly suited for this high-risk population for renal failure.     

肝衰竭合并侵袭性肺曲霉菌病的危险因素和胸部影像特征分析

目的：探讨肝衰竭患者合并侵袭性曲霉菌病的临床特征、危险因素及胸部影像特征。方法对20例肝衰竭合并肺侵袭性曲霉菌病（IPA）的临床特征、实验室指标以及胸部CT进行回顾性分析。结果463例肝衰竭患者中发生侵袭性曲霉菌病20例（4.3%）,其中药物性肝病7例、自身免疫性肝病6例、代谢性肝病2例、乙型肝炎5例。肝衰竭合并IPA的危险因素包括：70%患者长期使用2种以上抗生素,60%患者有糖皮质激素暴露史,55%患者CD4＋T淋巴细胞计数≤400/mm3。胸部平片缺乏特征性改变,而肺部CT改变以双肺多发结节和近胸膜楔形实变最为常见,晕轮征和新月形空气征较少。5例IPA患者经伏立康唑治愈,其余死亡或自动出院。结论肝衰竭患者易发侵袭性肺曲霉菌病,多数患者具有深部真菌感染的危险因素,胸部CT特征对于肝衰竭合并IPA具有重要的提示价值。     

A case of successful resection after long-term medical treatment of invasive pulmonary aspergillosis following living donor liver transplantation

Invasive pulmonary aspergillosis (IPA) occurs in 1.5 to 10% of liver transplant recipients. Of the fungal infections, IPA is the most difficult to treat and the most frequently life-threatening. However, the best treatment strategy remains controversial. The patient was a 53-year-old woman who underwent living donor liver transplantation (LDLT) because of subacute fulminant hepatic failure due to autoimmune hepatitis. Aspergillus fumigatus was detected in the sputum taken intraoperatively by bronchial suction. A computed tomogram of the lung 7 days after LDLT showed fungal balls in the left lung. IPA was diagnosed. Since the patient suffered from pulmonary edema postoperatively and fungal balls occupied a greater part of the left lung, conservative therapy using micafungin, amphotericin B, and itraconazole was first selected. However, the fungus balls did not completely disappear. Moreover, brain abscess probably resulting from IPA dissemination was detected. Lung resection was performed as reduction surgery, and salvage treatment using voriconazole was done for a brain abscess. Septate hyphae of Aspergillus fumigatus were identified in the lung specimen. We concluded that for patients with IPA after LDLT, pulmonary resection should be done as soon as possible before deterioration of IPA and complication due to acute cellular rejection.