Incidence of fungal infections in a solid organ recipients dedicated intensive care unit

Invasive fungal infections are a significant cause of morbidity and mortality for patients undergoing solid organ transplantation. Our aim was to evaluate the incidence of invasive fungal infections in solid organ recipients within a dedicated intensive care unit (ICU). MATERIALS AND METHODS: From May 2002 to May 2005, 278 patients undergoing solid organ transplantation (105 liver, 142 kidney, 20 lung, 2 combined liver-kidney, 9 combined pancreas-kidney) were admitted to our posttransplant intensive care unit. We retrospectively analyzed data obtained from the ICU stay. Fungal infection was defined by positivity of normally sterile biological samples and by elevated positivity of normally non sterile biological samples. We did not consider superficial fungal infections and asymptomatic colonizations. RESULTS: Forty-six patients (16.5%) developed a fungal infection; at least one mycotic agent was isolated from each patient. Candida albicans was the most common pathogen, isolated from 71 % of infected patients (33 of 46). Infected patients showed a mortality rate of 35%, while that for non infected recipients was 3.5%. Total length of ICU stay was the most significant risk factor among infected patients (30.26 days vs 5.04 days P < .0001). Mean time between transplantation and first positive samples was 6.17 days (SD 8.88). CONCLUSION: Fungal infections in solid organ transplant patients are a major issue because of their associated morbidity and mortality. Candida albicans was the most common pathogen and total length of ICU stay was the most important risk factor.     

Vancomycin-resistant Enterococcus in liver transplant patients.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) infection is emerging in the transplant population, and there is no effective antibiotic therapy available. The aims of this retrospective review were to (1) investigate the outcome of and (2) identify common characteristics associated with VRE infection and colonization in orthotopic liver transplant (OLTx) candidates. METHODS: From October 1994 through September 1998, 126 isolates of VRE were identified in 42 of 234 OLTx recipients and 5 OLTx candidates who did not proceed to transplantation. Data were collected by patient chart review or from a computerized hospital database. RESULTS: The 1-year mortality rate with VRE infection was 82%, and with VRE colonization, 7%. This mortality rate contrasts with a 14% 1-year mortality for non-VRE transplant patients (P <0.01, infected patients and colonized patients). Characteristics of VRE colonized and infected patients included recent prior vancomycin (87%), coinfection by other microbial pathogens (74%), recent prior susceptible enterococcal infection (72%), concurrent fungal infection (62%), additional post-OLTx laparotomies (47%), and renal failure (Cr >2.5 mg/dL or need for dialysis; 43%). Biliary complications were seen in 52% of post-OLTx VRE-infected or VRE-colonized patients (versus 22% in non-VRE transplant patients, P <0.05). CONCLUSION: VRE infection is associated with a very high mortality rate after liver transplantation. The incidence of biliary complications prior to VRE isolation is very high in VRE-infected and VRE-colonized patients. The most common characteristics of VRE patients were recent prior vancomycin use, recent prior susceptible enterococcal infection, coinfection with other microbial pathogens, and concurrent fungal infection. With no proven effective antimicrobial therapy for VRE, stringent infection control measures, including strict and limited use of vancomycin, must be practiced.     

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。     

Fungal infections in liver transplant recipients

Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.     

Comparison of fungal and nonfungal infections in a broad-based surgical patient population

BACKGROUND: Our aim was to compare fungal and nonfungal infections among a diverse surgical patient population. METHODS: Data on all hospital-acquired infectious episodes among surgical intensive care unit and ward patients were collected prospectively over six years at a single university hospital. The relationships between fungal and nonfungal infection and over 100 variables were examined using univariate and multiple logistic regression analysis. RESULTS: During the study period, 3,980 infectious episodes were identified; 554 were associated with fungal infection. Multiple logistic regression analysis demonstrated that markers of severity of acute illness (higher APACHE II scores and white blood cell counts, greater transfusion of cellular blood products, mechanical ventilator dependency, and prior infection) predicted fungal infection, whereas markers of chronic illness (comorbidities) did not independently predict either fungal or nonfungal infection. Patients with fungal infection were treated with more antibiotics for longer periods of time, had prolonged lengths of stay, and more often died compared with nonfungal infection patients. A separate multiple logistic regression analysis demonstrated that both fungal infection and the number of fungal sites of infection independently predicted mortality. Of all fungal isolates, only Candida albicans and Aspergillus spp. independently predicted mortality. CONCLUSIONS: Fungal infections differ significantly in character and outcomes from nonfungal infections among surgical patients.     

Fungemia Associated with Left Ventricular Assist Device Support

Abstract  Objective: Infections remain an important complication of left ventricular assist device (LVAD) support. While relatively uncommon, fungal infections present a serious concern given a high association with adverse events including death. We sought to further characterize the epidemiology of fungemias during LVAD support. Methods: Retrospective review of 292 patients receiving LVAD support from October 1996 to April 2009 at the University of Michigan Health System was done. Results: Seven cases of LVAD-associated fungemia were observed during the study period (0.1 infections/1000 days of device support). Five patients had infection with Candida species and two with Aspergillus species. The two patients with Aspergillus infection presented with disseminated disease, quickly dying of multiorgan failure, and sepsis. All five patients with Candida infections were successfully treated with systemic antifungal therapy along with transplantation in four of five patients. The fifth patient is receiving mechanical support as destination therapy. He remains on long-term suppression with high-dose fluconazole. Conclusions: Fungal infections appear to be a rare but serious complication of LVAD support. Future studies should aim to improve our understanding of risk factors for fungal infection during mechanical support, especially disseminated Aspergillus . Short-term perioperative antifungal prophylaxis with fluconazole appears to be an effective and reasonable approach to prevention.     

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy

BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.     

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.     

Clinical spectrum of fungal infections after orthotopic liver transplantation

During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%). Candida species accounted for 83.5% of cases. Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16). The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation. Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications. Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%). Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.     

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.     

Vancomycin-resistant enterococci in livertransplant recipients

BackgroundVancomycin-resistant Enterococcus (VRE)infection is emerging in the transplant population, and there is no effective antibiotic therapy available. The aims of this retrospective review were to (1) investigate the outcome of and (2) identify common characteristics associated with VRE infection and colonization in orthotopic liver transplant (OLTx) candidates.MethodsFromOctober 1994 through September 1998, 126 isolates of VRE were identified in 42 of 234 OLTx recipients and 5 OLTx candidates who did not proceed to transplantation. Data were collected by patient chart review or from a computerized hospital database.ResultsThe 1-year mortalityrate with VRE infection was 82%, and with VRE colonization, 7%. This mortality rate contrasts with a 14% 1-year mortality for non-VRE transplant patients (P < 0.01, infected patients). Characteristics of VRE colonized and infected patients included recent prior vancomycin (87%), coinfection by other microbial pathogens (74%), recent prior susceptible enterococcal infection (72%), concurrent fungal infection (62%), additional post-OLTx laparotomies (47%), and renal failure (Cr > 2.5 mg/dL or need for dialysis; 43%). Biliary complications were seen in 52% of post-OLTx VRE-infected or VRE-colonized patients (versus 22% in non-VRE transplant patients, P < 0.05).ConclusionVREinfection is associated with a very high mortality rate after liver transplantation. The incidence of biliary complications prior to VRE isolation is very high in VRE-infected and VRE-colonized patients. The most common characteristics of VRE patients were recent prior vancomycin use, recent prior susceptible enterococcal infection, coninfection with other microbial pathogens, and concurrent fungal infection. With no proven effective antimicrobial therapy for VRE, stringent infection control measures, including strict and limited use of vancomycin, must be practiced.     

Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective,multicenter, case-controlled study

BACKGROUND: This study determines whether the spectrum, risk factors, and outcome of invasive candidiasis in liver transplant recipients have changed. METHODS: Thirty-five consecutive liver transplant recipients with invasive candidiasis were prospectively studied in a case-controlled, multicenter study. One control was matched with the case for duration of hospitalization and the other for antibiotic use so that risk factors unique in liver transplantation could be elicited. RESULTS: In matched-pair analysis, antibiotic prophylaxis for spontaneous bacterial peritonitis (odds ratio [OR] 8.3, P=0.002), posttransplant dialysis (OR 7.6, P=0.0009), and retransplantation (OR 16.4, P=0.0018) were independently significant predictors of invasive candidiasis. Candida spp. included C. albicans in 65% of patients, C. glabrata in 21%, C. tropicalis in 9%, C. parapsilosis in 3%, and C. guilliermondii in 3%. Patients with C. albicans infections were less likely to have received antifungal prophylaxis than those with non-albicans Candida infections (13.6% vs. 50%, P=0.04). The mortality rate was 36.1% for the cases and 2.8% for the controls (OR 25.0, 95% confidence interval, 6.2-100.5, P=0.0002). Non-albicans Candida infections (P=0.04) and prior antifungal prophylaxis (P=0.05) correlated with poorer outcome in the cases. CONCLUSIONS: Our study has identified predictors for Candida infections in the current era that have implications relevant for targeting the prophylaxis toward the high-risk patients. Routine use of antifungal prophylaxis warrants concern given the emergence of non-albicans Candida spp. as significant pathogens after liver transplantation and higher mortality in patients with these infections.     

普通外科病人真菌败血症的临床研究

目的探讨普通外科真菌败血症的发生特点、病原菌的种类及防治策略。方法回顾性分析2001年3月至2005年12月间南京军区南京总医院普通外科收治的94例真菌败血症病人的易感因素、病原学特点及治疗效果。结果易感因素主要为使用广谱抗生素、中心静脉插管、全胃肠外营养、入住重症监护病房。94例病人分离出94例菌株。非白色念珠菌是主要致病真菌。94例经抗真菌治疗者中37例死亡。结论真菌败血症多发生在存在腹腔感染病人。念珠菌属是主要致病真菌，其中以非白色念珠菌为主。对高危病人应重视病原学检查及药物敏感性测定，消除易感因素，及时合理选用抗真菌药物和肠内营养有望进一步改善预后。     

真菌感染性胰腺坏死的临床分析：附46例报告

目的:分析真菌感染性胰腺坏死(IPN)的发病情况以及外科治疗与临床转归。方法:回顾2010年1月—2018年7月间中南大学湘雅医院胰胆外科连续收治的145例IPN患者的临床资料,对其中真菌性IPN病例进行重点分析。结果:145例IPN中,真菌性IPN共46例(31.7%);年代分布分析显示,近2年(2017—2018)真菌性IPN所占比例最高,达40.7%;46例患者均为念珠菌感染,主要为白色念珠菌(25例次),其次为光滑念珠菌(14例次)和热带念珠菌(7例次)。46例患者中,41例采取升阶梯治疗,5例采取降阶梯治疗。真菌性IPN患者的外科干预总次数159次,平均外科干预次数明显高于非真菌性IPN患者(3.5次/例vs. 2.7次/例,P0.05)。全组IPN患者的病死率为22.1%(32/145),其中真菌性IPN患者的病死率为17.3%(8/46),非真菌性IPN患者为24.2%(24/99),两者差异无统计学意义(P0.05)。46例患者中,4例患者合并真菌血症,合并真菌血症者的病死率较非真菌血症的病死率明显增高[75%(3/4)vs.14.3%(5/42),P0.05]。结论:真菌性IPN的发病率呈上升趋势。虽然真菌感染并不增加IPN患者的病死率,但往往需要更多的外科干预,且当合并真菌血症时,患者的病死率明显升高。因此,合理选用抗真菌药物及彻底的感染源控制是治疗真菌性IPN的关键。     

Infectious complications after kidney transplantation: current epidemiology and associated risk factors

BACKGROUND: The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. METHODS: This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. RESULTS: We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR=4.5 and 2.9, p=0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR=3.3 and 2.5, p=0.009 and 0.047, respectively). CONCLUSION: This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal.     

Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and Effectiveness

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients.
This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality.
Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.     

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。     

Enteral fluconazole is well absorbed in critically ill surgical patients

BACKGROUND: Enteral fluconazole, a triazole antifungal agent with an excellent oral bioavailability, has not been widely studied in critically ill surgical patients. METHODS: During a randomized placebo-controlled trial of enteral fluconazole (N = 130) versus placebo (N = 130) for the prevention of fungal infections in critically ill surgical patients, trough fluconazole levels were measured after the loading dose and 3 times weekly during intensive care unit stay. Minimum inhibitory concentrations (MICs) for fluconazole were measured on all infecting Candida isolates. RESULTS: Four hundred sixty-seven serum samples were assayed for fluconazole levels in 121 patients. The most common infecting fungal species was Candida albicans, isolated in 14 of 31 infections (45%). Other infecting species were C glabrata, C tropicalis, and C parapsilosis. Mean fluconazole levels were above the highest MIC for C albicans and C parapsilosis in all but 5 patients (4%). Mean fluconazole levels were below the median MIC for C glabrata in 93 of 121 patients (77%). No significant relationship was seen between fluconazole levels and risk for fungal infection. CONCLUSIONS: Serum fluconazole levels are above the MIC of most yeast species found in these patients. These levels may not be above the MIC of C glabrata, the second most common Candida isolate causing infection in this study.     

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。     

Late mortality after orthotopic liver transplantation.

BACKGROUND: Mortality within the first year after orthotopic liver transplantation (OLTx) is usually due to infection or allograft failure. Late complications leading to death after OLTx have not been extensively evaluated. The aim of this study was to determine the incidence of late mortality and to identify the most common causes and risk factors associated with late mortality after OLTx. METHODS: A total of 479 OLTx were performed in 459 patients (320 males, 139 females; mean age 47 years, range 13 to 69) between September 1991 and April 2000. All patient deaths among liver transplant recipients who survived more than 1 year after transplantation (follow-up mean 3.4 years, median 3, range 1 to 8.6) were reviewed. RESULTS: In all, 122 allografts (24%) were lost in 109 patients during the study period (24%). Seventy-five allografts were lost in 69 patients by 1 year (15%). Forty-seven allografts were lost in 40 patients who survived at least 1 year (9.6%). Actuarial survivals at 2 years, 5 years, and 9 years were 95%, 85%, and 80%, respectively (based on 100% survival at 1 year). The causes of the late mortality were malignancy (9 patients), disease recurrence (8), late infection (6), renal failure complications (5), cardiovascular complications (4), chronic rejection (3), gastrointestinal hemorrhage (2), medication noncompliance (1), and unknown (2). CONCLUSIONS: Malignancy and disease recurrence are the major causes of late mortality among adult OLTx recipients. Pharmacologic immunosuppression is associated with many of the causes of late mortality. Advances in immunosuppression with less toxicity may improve long-term survival after OLTx.