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,合理应用抗真菌药物,以达到良好治疗目的 .方法 回顾性分析我院肝移植中心1997 年7月至2008年7月实施的156 例肝移植患者发生真菌感染的情况.结果 156 例肝移植患者,有14例发生真菌感染,占9.0%;死亡7例,占50.0%.其中白色念珠菌3例,热带念珠菌2例,曲霉菌8例,毛霉菌1例.感染部位主要为肺部(8 /14,57.1%),血液(5/14,35.7%)和腹腔(1/14,7.1%),泌尿系统少见(0/14,0%).氟康唑治疗有效者占23.1%,伊曲康唑治疗有效者占7.7%,卡泊芬净治疗有效者7.7%,总有效率为53.8%.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、伊曲康唑及卡泊芬净等药物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。     

原位肝移植术后真菌感染43例次诊治体会

目的 探讨原位肝移植术后真菌感染的诊断、治疗及预防。方法 回顾总结为175位患者所施行的180次原位肝移植的临床资料，并对可能导致真菌感染的危险因素进行统计学分析。结果 全组29例患者出现43例次真菌感染，感染率为16．6％(29／175)。其中念珠菌占98％(42／43)，曲霉菌2％(1／43)。发病中位时间为术后26d(3～96d)。常见感染部位依次是肺部37％(16／43)，肠管19％(8／43)和血液16％(7／43)。26例患者接受氟康唑治疗，感染严重的8例患者改用脂质体两性霉素B治疗。病死率45％(13／29)，直接与真菌感染有关的病死率为4．0％(7／175)。全胃肠外营养时间较长、抗生素治疗超过3周或出现肝动脉并发症的患者真菌感染的发生率显著增加。结论 真菌感染是影响肝移植生存率的重要原因之一。最常见的感染部位和病原菌分别是肺部和念珠菌。减少各种危险因素将有助于降低真菌感染的发生率。早期诊断和及时治疗是治愈的关键，严重的真菌感染应及时给予两性霉素B或其脂质体治疗。     

重症急性胰腺炎合并深部真菌感染的预防和治疗

目的：探讨重症急性胰腺炎（SAP）合并深部真菌感染的预防和治疗措施。方法：将1998年7月－2002年6月收治的70例SAP病人随机分3组：大蒜素预防组、氟康唑（小剂量）预防组、对照组，比较各组的真菌感染发生率，治疗后真菌清除率及死亡率。结果：大蒜素组真菌感染率明显低于对照组（16％：30％，P＜0．05）及氟康唑组（9％：30％，P＜0．01）。真菌感染发生后，采用治疗剂量的氟康唑和两性霉素B对大蒜素组、对照组的真菌感染病人有效，而对氟康唑组真菌感染病人无效。结论：预防性应用大蒜素、小剂量氟康唑均可明显降低SAP的深部真菌感染发生率。真菌感染发生后，如氟康唑治疗无效，应及时改用两性霉素B。     

肝移植术后肺曲霉菌感染的诊治

目的：探讨肝移植术后肺曲霉菌感染的诊治方法。方法：肝移植术后患者常规进行痰培养,应用二性霉素B、伊曲康唑和氟康唑等抗真菌药物治疗,回顾性分析了3例肺部曲霉菌感染患者的诊治经过。结果：54例肝移植患者有3例发生肺曲霉菌感染,治愈1例,死亡2例。结论：（1）过度免疫抑制是导致肺曲霉素感染的重要因素。（2）二性霉素B治疗肺曲霉感染有效。（3）为降低二性霉素B的毒副作用和增强疗效,治疗方法上可采用渐进性给药、间断性给药、低浓度给药、联合给药,真菌培养阴性后用伊曲康唑巩固治疗2-3周。     

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.     

肾移植术后肺部真菌感染的诊断与治疗

目的：探讨肾移植术后肺部真菌感染的诊断与治疗。方法：回顾性分析25例肾移植术后肺部真菌感染患者的临床资料，其中男16例，女9例，平均年龄46．2岁，发病时间平均为术后137．8天。结果：25例患者中，白色念珠菌感染6例，光滑念珠菌感染感染1例，假丝酵母菌感染1例，热带念珠菌感染1例，曲霉菌感染1例，新型隐球菌感染1例，镜检见菌丝感染2例，培养阴性12例；合并感染11例。13例培养或镜检阳性者中，采用伊曲康唑治疗有效10例，死亡1例，2例改用两性霉素B脂质体治疗，均康复；12例培养或镜检均阴性者中，采用抗细菌和抗病毒治疗均无效，其中7例采用伊曲康唑治疗3天，5例有效，2例无效后改用两性霉素B脂质体治疗，5例应用醋酸卡泊芬净治疗，患者均康复。本组25例患者在积极抗真菌的同时给予呼吸支持、调节免疫抑制剂剂量、经验性联合抗微生物、小剂量激素及其他支持治疗等，24例康复出院，1例死亡。结论：肺部真菌感染是。肾移植术后常见并发症。早期诊断并应用新型抗真菌药、调节免疫抑制剂剂量、给予经验性联合抗微生物、小剂量激素等，治疗效果良好，治愈率高。     

肝移植术后预防性抗真菌治疗的系统性回顾和网状Meta分析

<正>肝移植患者侵袭性真菌感染(IFI)可导致极高的病死率,但是否应该进行预防性治疗以及最佳药物仍无确切定论。来自英国的学者系统性回顾了肝移植术后预防性抗真菌治疗的随机对照试验,采用随机效应Meta分析和贝叶斯网状Meta分析比较,共有14项研究符合纳入标准,报道了氟康唑、脂质体两性霉素B(L-Am B)伊曲康唑、米卡芬净和安慰剂的效果比较。经分析,与安慰剂比较,预防性抗真菌治疗降低了最终证实为IFI的发生率〔优势比(OR)=0.37,95%可信区间(95%CI)=0.19~0.72,P=     

伊曲康唑在肝移植术后真菌感染的预防和治疗中的价值

在临床肝移植中，由于免疫抑制剂、广谱抗生素等药物的大量使用，侵袭性真菌感染（invasive fungal infection，IFI）的发生率近年来呈上升趋势。IFI的发生降低了肝移植患者的存活率，而且大大增加了治疗成本。因此，提高真菌感染的预防和治疗水平已刻不容缓。我们对2004年至2005年60例肝移植患者术后采用两种不同的预防和治疗真菌感染的对策，根据治疗结果的差异，对伊曲康唑在肝移植术后IFI的预防和治疗中的价值进行了探讨。     

Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients

BACKGROUND: Liver transplant recipients at high risk for serious fungal infections frequently receive fluconazole or an amphotericin B preparation for antifungal prophylaxis. Because of concerns about fungal resistance with fluconazole, safety with amphotericin B, and the cost of lipid formulations of amphotericin, alternative prophylactic regimens are needed. In this randomized, controlled trial, we compared the efficacy and safety of oral itraconazole solution with intravenous/oral fluconazole for prevention of fungal infections. METHODS: Adult liver transplant recipients were randomized to receive either oral itraconazole solution (200 mg every 12 hr) or intravenous/oral fluconazole (400 mg every 24 hr). Each study drug was started immediately before transplant surgery and continued for 10 weeks after transplantation. Patients were evaluated for fungal colonization, proven invasive or superficial fungal infection, drug-related side effects, and death. RESULTS: Fungal colonization decreased from baseline to week 8 after transplantation in both the itraconazole patients (67% to 25%, P<0.001) and the fluconazole patients (77% to 30%, P<0.001). Proven fungal infection developed in 9 (9%) of 97 itraconazole patients and in 4 (4%) of 91 fluconazole patients (P =0.25). The number of proven invasive fungal infections (seven with itraconazole [7%], three with fluconazole [3%]) and proven superficial fungal infections (two with itraconazole [2%], one with fluconazole [1%]) were also similar in both groups of patients. Organisms causing infection were (four patients), (three patients), and species (two patients) in the itraconazole group and (two patients), (one patient), and species (one patient) in the fluconazole group. Mortality from fungal infection was very low and occurred in only 1 (0.5%) of 188 patients. Except for more frequent gastrointestinal side effects (nausea, vomiting, diarrhea) with itraconazole, both itraconazole and fluconazole were well tolerated and not associated with any hepatotoxicity. Mean trough plasma concentrations of itraconazole were greater than 250 ng/mL throughout the study and were not affected by H -receptor antagonists or antacids. CONCLUSION: Oral itraconazole solution has adequate bioavailability in liver transplant recipients for effective antifungal prophylaxis. Similar to fluconazole, prophylactic oral itraconazole decreases fungal colonization and is associated with a low incidence of serious or fatal fungal infections. Except for gastrointestinal side effects, oral itraconazole solution is well tolerated and has no significant hepatotoxicity.     

Role of Liposomal Amphotericin B Prophylaxis After Liver Transplantation Compared With Fluconazole for High-Risk Patients. Impact on Infections and Mortality Within one Year

Background

Fungal infections are still one of the most important issue in liver transplant patients, contributing considerably to both morbidity and mortality. Few studies have been published comparing antifungal protocols for their impact on liver transplant (OLT) patients. The aim of this study was to evaluate the effects of liposomal amphotericin B compared with fluconazole prophylaxis on morbidity and mortality after liver transplantation.

Methods

We evaluated all 44 patients undergoing OLT from January 2006 to January 2009 who were enrolled and randomized to undergo treatment with Amphotericin B (3 mg/kg/d; group A = 25 patients) or fluconazole (800 mg Loading dose and thereafter 400 mg/d according to renal parameters and immunosuppressant trough levels; group B = 18 patients) for at least 7 to 14 days with 12 months follow-up after liver transplantation. A multivariate analysis assessed factors associated with infections and mortality.

Results

Neither antifungal prophylaxis was associated with a fungal episode; however, group A patients experienced fewer bacterial infectious episodes (Mann-Whitney U test P < .05). Furthermore, no renal impairment was observed in either groups. Nonetheless, patients undergoing fluconazole prophylaxis showed significant increases in immunosuppressive trough levels requiring dose adjustment.

Conclusion

We observed comparable results of fluconazole and liposomal amphotericin B to prevent invasive fungal infections throughout 12 months after surgery. The latter drug was associated with fewer bacterial infections after liver transplantation.     

Antifungal prophylaxis in liver transplant recipients: a randomized placebo-controlled study

The aim of this study was to evaluate the efficacy of two antifungal prophylaxis regimens in liver transplant recipients. One hundred and twenty-nine consecutive recipients were randomized to receive sequential treatment with intravenous liposomal amphotericin B + oral itraconazole, intravenous fluconazole + oral itraconazole, or intravenous and oral placebo. Frequency and incidence of mycotic colonization, local and systemic infection of mycotic origin, causes of death, and possible risk factors for mycotic infection were evaluated. The incidence of mycotic colonization was higher in the placebo group ( P<0.01), but there was no significant difference in the incidence of infection between the three groups. Pre-transplant colonization, severity of liver disease, and graft rejection were all risk factors for the development of fungal infection. The routine use of antifungal prophylaxis for all liver transplant recipients does not seem to be justified.     

2016至2018年某医院真菌血流感染者流行病学特征及耐药性分析

目的分析真菌性血流感染的病原菌分布以及耐药特征，为真菌血流感染的早期合理用药提供理论依据。 方法回顾性分析武汉大学人民医院2016年1月至2018年12月收治的真菌性血流感染者的菌群、科室分布以及耐药性。 结果入组192例真菌血流感染者的血培养样本中共分离192株真菌，其中白色念珠菌检出率为31.77%（61/192），其次热带念珠菌检出率为18.75%（36/192）；重症医学科检出率最高为33.85%（65/192）。所有菌株均对两性霉素B敏感，对其他抗菌药物耐药率分别为5-氟胞嘧啶4.49%（9/192）、伊曲康唑5.73%（11/192）、氟康唑10.94%（21/192）和伏立康唑11.46%（22/192）；除两性霉素B外，2016至2018年真菌对其他抗菌药物的耐药率均逐年上升，其中2018年所分离192株光滑念珠菌对伊曲康唑耐药菌率达46.7%。 结论真菌血流感染病原菌以念珠菌属为主，对目前抗真菌药物具有较高敏感性，但耐药率逐年上升，加强监测血培养病原菌变化及耐药趋势对指导临床用药至关重要。     

Antifungal drugs in the treatment of systemic candidiasis: susceptibility to antifungal drugs, drug resistance, pharmacological data

The available antifungal agents are amphotericin B (conventional or lipid formulation), flucytosin and azole derivatives (ketoconazole, fluconazole, itraconazole). The main target of these molecules are a specific compound of fungal membrane, ergosterol. Determination of the fungal sensitivity to antifungal drugs is difficult and no consensus has been achieved so far. Minimal inhibitory concentrations are poor predictors of clinical success or failure. A good correlation between in vitro and in vivo results has been observed only in patients with oropharyngeal candidiasis associated with HIV infection. Combinations of antifungal drugs are currently under study. The role of hemopoietic growth factors (G-CSF, GM-CSF) as an adjuvant has not been fully established. New antifungal drugs (triazole derivatives, echinocandins) should be available within months.     

Prospective interventional study to evaluate the efficacy and safety of liposomal amphotericin B as prophylaxis of fungal infections in high-risk liver transplant recipients

INTRODUCTION: Invasive fungal infections are a life-threatening complication in transplant recipients. The prevalence of fungal infection after orthotopic liver transplantation (OLT) is 5% to 42%. The most common isolated pathogens are Candida and Aspergillus species. High-risk liver transplant recipients are more susceptible to the development of invasive fungal infections, with prevalence >40% and mortality rates of 78% to 100%. The strategy for fungal prophylaxis in this population has not been defined. PATIENTS AND METHODS: Among 100 consecutive OLT followed for 28 months, 21 recipients (15 men, overall mean age of 48.5 years, range 23-65 years) were considered to be high risk for the development of fungal infections when they presented at least one of the following criteria: acute liver failure, assisted ventilation >7 days, retransplantation, relaparotomy, antibiotic therapy >14 days, transfusion requirements >20 red blood cells units, and/or biliary leakage. This group received intravenous liposomal amphotericin B (1 mg/kg/d for 7-10 days). RESULTS: One-year survival in the high-risk group was 80%. Prevalence of invasive fungal infection was 9.5%. No Candida infection was observed. Two patients developed Aspergillus infection: an abdominal aspergillosis treated with percutaneous drainage and liposomal amphotericin B (5 mg/kg/d) showed a favorable clinical outcome. The other patient who developed brain aspergillosis died 25 days after OLT. Adverse events related to the drug were hypokalemia (n = 2), back pain (n = 3), and renal dysfunction (n = 2). None of these events required withdrawal of the prophylaxis regimen. CONCLUSION: In our series, prophylaxis with liposomal amphotericin B in high-risk liver graft recipients showed a low rate of severe fungal infections. More studies are needed in order to determine the highest risk population and the best drug dosage.     

Epidemiology and susceptibility to antifungal agents of fungi isolated from clinical specimens from patients hospitalized in the Department of General and Liver Surgery of the Medical University of Warsaw

The aim of this study was to analyze the type and antibiotic susceptibility of fungi isolated from clinical specimens obtained from patients hospitalized in the Department of General, Transplantation and Liver Surgery of the Medical University of Warsaw between 2000 to 2002. Among the 326 clinical samples found to be positive on mycological culture, 356 strains were cultured. The most common isolates were yeastlike fungi of the genus Candida 334 (93.8%), while others included 33 other types (6.2%). The most commonly isolated species were Candida albicans, 194 strains (54.5%); Candida glabrata, 68 (19.1%); Candida krusei, 20 (5.6%); Candida inconspicua, 20 (5.6%); Candida tropicalis, 17 (4.8%); and Candida parapsilosis, 6 (1.7%). Upon testing for susceptibility to antifungal agents, all strains were susceptible to amphotericin B, while 43.8% of strains showed intermediate susceptibility to fluconazole and 25.3%, to itraconazole. Control of fungal infections in transplant and in immunocompromised patients is hindered by the low percentage of strains susceptible to commonly used antifungal agents, particularly of the triazole group.     

经内镜逆行胰胆管造影术诊断和治疗肝移植术后胆道真菌感染二例

目的探讨肝移植术后胆道真菌感染诊治的有效方法。方法2例肝移植术后临床表现有严重胆系感染者,经内镜鼻胆管引流获取胆汁进行涂片和/或培养证实胆道真菌感染合并细菌感染。根据胆汁培养和药物敏感试验结果进行针对性抗细菌治疗,并经鼻胆管给予氟康唑胆道冲洗和联合予以氟康唑或伊曲康唑静脉治疗。结果2例患者胆系真菌感染的病原菌分别为光滑假丝酵母菌及热带假丝酵母菌,经鼻胆管局部氟康唑冲洗治疗时间分别为19d和30d,静脉抗真菌治疗时间分别为27d和56d;2例患者均治愈。经13个月的随访未见胆系真菌感染复发。结论经内镜逆行胰胆管造影(ERCP)并获取胆汁进行真菌涂片、培养是诊断胆道真菌感染的关键。经鼻胆管局部给予氟康唑联合静脉抗真菌治疗胆道真菌感染应为一种安全有效的方案。保持胆道引流通畅对于胆道真菌感染治疗是极其重要的。