Targeted Prophylaxis With Amphotericin B Lipid Complex in Liver Transplantation

Abstract

The purpose of this study is to prospectively evaluate a strategy in which prophylaxis with amphotericin B lipid complex at 3 different dosages was targeted to liver transplant recipients at high risk for the development of invasive fungal infection (IFI). High risk was defined as a postoperative requirement for prolonged (>5 days) intensive care unit (ICU) treatment. Consecutive high-risk patients were administered prophylaxis with amphotericin B lipid complex from day 5 after orthotopic liver transplantation (OLT) until ICU discharge or death. The first 10 eligible patients were administered 5 mg/kg/d, the next 10 patients were administered 2. I nvasive fungal infection (IFI) has a high mortality after orthotopic liver transplantation (OLT). In early studies, the incidence of IFI in this setting ranged from 18% to 42%, and the associated mortality rates were 50% to 78%. 1-6 Candida species accounted for the majority of infections, and many patients infected with Candida organisms survived. In contrast, infections caused by Aspergillus species were nearly always fatal. 2,3,6 We showed that in liver transplant recipients considered high risk for IFI, fluconazole prophylaxis reduced the incidence of invasive candidiasis 7 but was complicated by the emergence of fluconazole-resistant fungi and failed to prevent invasive aspergillosis. 8 A recent randomized, placebo-controlled trial of liver transplant recipients showed that prophylaxis with fluconazole was associated with a decrease in fungal colonization and fewer deaths related to IFI, but did not improve overall survival. 9 Amphotericin B formulations are the agents of choice for the treatment of infections caused by Aspergillus species. Concerns about toxicity related to conventional amphotericin B 10 have inhibited its use as antifungal prophylaxis in OLT. The development of new lipid-based formulations of amphotericin B that are less toxic than the conventional form of the drug has led to renewed interest in the potential prophylactic use of this agent. [11][12][13][14] In 1 study, prophylaxis with liposomal amphotericin B (AmBisome; Nexstar, San Dimas, CA) at 1 mg/kg/d from the time of OLT reduced the incidence of IFI compared with placebo. 15 However, another group observed systemic mycosis in 4 of 58 liver transplant recipients treated according to a similar prophylactic schedule with AmBisome. 16 Amphotericin B lipid complex (Abelcet; The Liposome Co Ltd, London, England) is a lipid formulation with a high amphotericin B-lipid ratio (1:1), 17 and pharmacokinetic studies indicate that this formulation achieves lower peak plasma concentrations but greater tissue levels than the other lipid formulations of amphotericin B. 18 Furthermore, the in vitro activity of Abelcet against isolates of both Aspergillus and Candida organisms has recently been shown to be similar to that achieved by conventional amphotericin B but significantly greater than that achieved by AmBisome. 19 A randomized, prospective multicenter trial confirmed that Abelcet was as effective as...

Antifungal Management Practices in Liver Transplant Recipients

“…Targeted prophylaxis however, was more often also directed towards Aspergillus than universal prophylaxis. These findings could possibly reflect data where antifungal prophylaxis in highrisk liver transplant recipients has comprised regimens that frequently target Aspergillus (7,10,(15)(16)(17). The leading choices for mold-active agents for antifungal prophylaxis were the echinocandins ( Table 2).…”

Epidemiology of fungal infections in liver transplant recipients: a six-year study of a large Brazilian liver transplantation centre

“…Proven IFI -Was defined as one of the following: at least one positive blood culture for Candida spp or other pathogenic fungi, a positive culture for a pathogenic fungus from a specimen collected from a normally sterile site, a positive culture for a pathogenic fungus from a biopsy specimen (taken across a potentially colonised mucosal surface) plus histopathology confirming fungal elements in tissue with local inflammation, evidence of fungal endophthalmitis based on dilated fundoscopic examination, positive histopathology for fungal elements in a deep tissue biopsy, positive cryptococcal or histoplasma antigen test and clinical or radiographic evidence consistent with cryptococcosis or histoplasmosis, a positive culture or histopathologic evidence of an endemic mycosis (blastomycosis, histoplasmosis or coccidioidomycosis), positive culture for a mould (Aspergillus spp, Fusarium spp, zygomycete) from a non-sterile body site together with clinical, histopathologic or radiologic evidence consistent with IFI, or evidence of fungal elements in a post mortem tissue evaluation (Singhal et al 2000, Pappas et al 2006.…”

AspergillusInfections in Transplant Recipients

“…At least three studies of liver transplant recipients have evaluated the efficacy of lipid formulations of amphotericin B (in dosages of 1 to 5 mg/kg/day) as antifungal prophylaxis (84,295,297). Of 31 patients who required Ն5 days in the intensive care unit and who received Abelcet (1 to 5 mg/kg/day) as antifungal prophylaxis, none developed invasive aspergillosis.…”