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一项前瞻性干预性研究,旨在评估脂质体两性霉素B对高危肝移植受者真菌感染的预防效果及安全性。

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

作者信息

Castroagudín J F, Pontón C, Bustamante M, Otero E, Martínez J, Tomé S, Conde R, Segade F R, Delgado M, Brage A, Galbán C, Varo E

机构信息

Liver Transplantation Unit, University Hospital, Santiago de Compostela, Spain.

出版信息

Transplant Proc. 2005 Nov;37(9):3965-7. doi: 10.1016/j.transproceed.2005.10.043.

Abstract

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.

摘要

引言

侵袭性真菌感染是移植受者的一种危及生命的并发症。原位肝移植(OLT)后真菌感染的发生率为5%至42%。最常见的分离病原体是念珠菌和曲霉菌种。高危肝移植受者更容易发生侵袭性真菌感染,发生率>40%,死亡率为78%至100%。该人群的真菌预防策略尚未明确。

患者与方法

在连续随访28个月的100例OLT患者中,21例受者(15例男性,总体平均年龄48.5岁,范围23 - 65岁)在出现以下至少一项标准时被认为有发生真菌感染的高风险:急性肝衰竭、辅助通气>7天、再次移植、再次剖腹手术、抗生素治疗>14天、输血需求>20个红细胞单位和/或胆漏。该组接受静脉注射脂质体两性霉素B(1 mg/kg/d,共7 - 10天)。

结果

高危组的一年生存率为80%。侵袭性真菌感染的发生率为9.5%。未观察到念珠菌感染。2例患者发生曲霉菌感染:1例腹部曲霉菌病经经皮引流和脂质体两性霉素B(5 mg/kg/d)治疗后临床结局良好。另1例发生脑曲霉菌病的患者在OLT后25天死亡。与药物相关的不良事件有低钾血症(n = 2)、背痛(n = 3)和肾功能不全(n = 2)。这些事件均未导致预防方案停药。

结论

在我们的系列研究中,高危肝移植受者使用脂质体两性霉素B预防显示严重真菌感染率较低。需要更多研究以确定最高风险人群和最佳药物剂量。

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