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。     

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。     

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。     

肝移植术后肺部感染34例诊治

目的探讨肝移植术后早期肺部感染的防治方法。方法对我院62例肝移植术后肺部感染34例患者的临床资料进行回顾性分析。结果痊愈27例，死亡7例。病原菌分析：痰培养有细菌、念珠菌阳性结果者27例，其中革兰氏阴性杆菌占51．9％，革兰氏阳性球菌占29．6％；真菌感染占18．5％，巨细胞病毒（CMV）感染1例，EB病毒感染1例，病原菌不明5例。结论革兰氏阴性杆菌是肝移植术后肺部感染的常见病原菌，术后第1周是肺部感染的高危时段。重视围手术期呼吸道管理及合理选用抗生素，是肝移植术后肺部感染防治的关键。     

肝移植术后真菌感染的防治新策略

目的探讨肝移植术后病人真菌感染的菌群变化特点和相应的防治策略。方法回顾性分析中山大学附属第三医院肝移植中心2004—2005年485例原位肝移植病人术后真菌感染的流行病学资料和药敏结果。结果485例病人中79例出现术后真菌感染，真菌感染率为16．3％，共分离出菌株88株，其中念珠菌71株（白色念珠菌35株，非白色念珠菌36株），曲霉菌17株，在菌群分布上2004年和2005年差异有显著性（P〈0．05）。念珠菌对氟康唑的耐药率2005年（60．0％）较2004年（33．3％）明显上升（P〈0．05）。结论肝移植术后非白色念珠菌和曲霉菌感染的比例逐渐上升，临床上应根据分离培养结果选择适当的抗真菌药物。     

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。     

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。     

背驮式肝移植术后神经精神并发症的防治

目的探讨背驮式肝移植患者术后神经精神并发症的防治对策。方法回顾性分析背驮式肝移植（PBLT）项目组235例中术后出现神经精神并发症的45例患者的病因、治疗反应及预后情况。结果神经精神并发症发生率19．1％（45／235），表现为躁狂者22例（48．9％），抑郁5例（11．1％），幻觉3例（6．7％），自杀倾向1例（2．2％），视物变形1例（2．2％），焦虑伴失眠8例（17．8％），适应障碍2例（4．4％），情感障碍3例（6．7％）；其中以谵妄样精神障碍最为多见，但大多数症状不严重，均治愈，仅1例昏迷患者头颅CT检查证实有颅内出血，抢救无效后死亡。结论背驮式肝移植术后神经精神并发症的发生率较高，但大多数病例症状较轻，预后较好。精神并发症出现后，针对不同病因，及时采用积极的综合治疗能改善患者的预后。     

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。     

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.     

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。     

Effects of fluconazole administration in critically ill patients: analysis of bacterial and fungal resistance

HYPOTHESIS: The administration of fluconazole in intensive care unit (ICU) patients leads to the emergence of bacterial and fungal resistance. DESIGN: Retrospective analysis of 2 patient cohorts: (1) critically ill patients treated in surgical, trauma, and medical ICUs between June 1997 and January 1999 who did and did not receive fluconazole; and (2) ICU patients with fungal infections and sensitivity testing results from June 1994 to December 1998. SETTING: University-affiliated tertiary care hospital. PATIENTS: The first cohort included 99 ICU patients with documented microorganism culture(s) who were treated with (n = 50) or without (n = 49) fluconazole; the second cohort included 38 patients with Candida species infection, identification, and antifungal susceptibility testing. RESULTS: Mortality (40% vs 20%; P = .03) and hospital length of stay (33.8 vs 25.6 days; P = .04) were higher in the patients treated with fluconazole compared with patients not treated with fluconazole. The ICU length of stay was also higher in patients treated with fluconazole (23.7 vs 15.1 days; P = .009). An increase in bacterial resistance occurred in patients after fluconazole treatment as opposed to bacterial resistance of patients who were treated for bacterial microorganism(s) without fluconazole (16% vs 4%; P = .049). Comparison of patient populations with Candida species identification before and after December 1997 showed an increase in Candida species resistance to fluconazole (11% vs 36%; P = .16), respectively. Fungal strains were dominated by a combination of Candida albicans and Candida glabrata in both populations (60% [before 1998] vs 82% [after 1998]), with an emergence of Candida non-albicans species tolerant to fluconazole. The amount of fluconazole administered and the number of patients receiving fluconazole treatment in the ICUs has also increased when comparing both periods. CONCLUSIONS: Comparison of critically ill patient populations with and without fluconazole treatment found increased mortality and longer hospital and ICU lengths of stay in the fluconazole-treated group. This group also had higher bacterial pathogen resistance to antibiotics after fluconazole administration compared with bacterial resistance of patients without fluconazole treatment. Our results warrant concern regarding worsening bacterial infections, increased mortality, and an increase in Candida resistance to fluconazole from increased use in ICU patients, with a shift in yeast infection that is more difficult to treat.     

A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality,acute cellular rejection,infections, and changes in the liver function tests while on caspofungin

Doria C, Bodzin AS, Vaccino S, Daskalakis C, Krawitz S, Ramirez CB. A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.
Clin Transplant 2011: 25: 569–575. © 2010 John Wiley & Sons A/S. Abstract: This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high‐risk patients. Post‐transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re‐transplantation; (ii) re‐operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re‐intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two‐thirds male and three‐quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment comparable (p = 0.540), and both better than no preventive treatment at all (OR = 0.15, p = 0.049, for caspofungin versus no preventive treatment; OR = 0.29, p = 0.085, for other antifungal versus no preventive treatment). Caspofungin appears to be an effective preventive agent against fungal infections when used in recipients of liver transplant designated as high risk for fungal infection. Usage of caspofungin in these patients does not carry an apparent increase in risk of death or acute cellular rejection, although we observed a significantly higher risk of AEs, especially acute renal failure (p = 0.001), in patients who received this agent.     

Candida parapsilosis peritonitis has more complications than other Candida peritonitis in peritoneal dialysis patients

Candida parapsilosis is the most prevalent pathogen of fungal peritonitis in peritoneal dialysis (PD). The difference between C. parapsilosis peritonitis and other C. species for clinical outcomes and treatment responses to fungal peritonitis remains unclear. This retrospective study of fungal peritonitis attempts to answer that question. A total 22 patients with fungal peritonitis in 762 PD patients were enrolled in this study. The mean age of the 22 patients, 9 males and 13 females, was 54.7 +/- 12.5 years with a mean PD duration of 39.7 +/- 33.4 months. Candida species accounted for 86% (19 cases) of fungal peritonitis and 41% (9 cases) were C. parapsilosis. Thirteen (59%) patients received fluconazole as monotherapy; others received either amphotericin B alone or in combination with fluconazole. Catheters were removed for all patients. The mean duration from peritonitis onset to catheter removal was 5.8 +/- 4.1 days. Eleven (50%) patients developed severe complications, with abscess formation or persistent peritonitis after catheter removal. C. parapsilosis peritonitis had a higher complication rate than other Candida species (78% versus 20%, p = 0.012). In patients who received fluconazole as monotherapy, the rate of severe complications of C. parapsilosis peritonitis was statistically higher than those of other Candida species (100% versus 29%, p = 0.013). Because of different severity and prognosis, C. parapsilosis peritonitis in PD patients should be treated more aggressively than other Candida species.     

Prophylactic fluconazole in liver transplant recipients: A randomized,double-blind,placebo-controlled trial

Background:Among persons who receive solid organ 0842 transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective.Objective:To evaluate the efficacy and safety of prophylactic0842 fluconazole in liver transplant recipients.Design:Randomized, double-blind, placebo-controlled trial. 0842Setting:University-affiliated transplantation center.0842Patients:212 liver transplant recipients who received fluconazole0842 (400 mg/d) or placebo until 10 weeks after transplantation.Measurements:Fungal colonization, proven superficial 0842 or invasive fungal infection, drug-related side effects, and death.Results:Fungal colonization increased in 0842 patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003).Conclusions:Prophylactic 0842 fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.     

A survey of anti-fungal management in lung transplantation

BACKGROUND: Fungal infections are an important complication of lung transplantation, but no controlled studies of their management have been performed. Knowledge of actual anti-fungal strategies may aid in the design of future prospective studies. METHODS: Thirty-seven of 69 active lung transplant centers, accounting for 66% of all US lung transplantations, responded to our survey. The survey focused on fungal surveillance, pre- and post-transplant prophylaxis, and approach to fungal colonization. RESULTS: The median number of lung transplantations performed by the centers in 1999 was 14 per year (range, 1-52), and median time that centers were in in operation was 9 years (range, 2-15 years). Seventy percent of centers had a transplant infectious diseases specialist. Pre-transplant fungal surveillance was performed by 81% of centers, with 67% of these surveying all patients and the remainder surveying only sub-sets of patients. Seventy-two percent of all centers started anti-fungal treatment if Aspergillus spp were isolated before transplantation. Itraconazole was the preferred agent (86%). After transplantation, 76% of centers gave anti-fungal prophylaxis, although 24% of these did so only in selected patients. Prophylactic agents in order of preference were inhaled amphotericin B (61%), itraconazole (46%), parenteral amphotericin formulations (25%), and fluconazole (21%); many centers used more than 1 agent. Prophylaxis was initiated within 24 hours by 71% and within 1 week by all centers. Median duration of prophylaxis was 3 months (range, <1 month-lifetime). All 37 centers used anti-fungal therapy if colonization with Aspergillus spp was detected for a median duration of 4.5 months. Itraconazole was the preferred agent. Only 59% of centers treated patients colonized with Candida spp. In a statistical analysis, centers with larger volumes were less likely to treat pre-transplant colonization with Candida spp but more likely to use agents other than itraconazole for post-transplant colonization with Aspergillus spp. Only 14% of centers engaged in any anti-fungal research at the time of the survey. CONCLUSIONS: The majority of surveyed lung transplant programs actively manage fungal infection with prophylaxis or pre-emptive therapy, despite the absence of controlled trials. This survey may provide an impetus and a basis for designing prospective studies.