Systemic mycoses during prophylactical use of liposomal amphotericin B (Ambisome^®) after liver transplantation

Abstract

We investigated the prophylactical administration of liposomal amphotericin B (Ambisome) in the early phase after liver transplantation (LTx). Fifty-eight patients received Ambisome prophylactically after LTx. Ambisome (1 mg kg-1 day-1) was given intravenously for 7 days after LTx. Immunosuppressive prophylaxis was cyclosporin A (CsA) based in 11 patients. Forty-seven patients had a tacrolimus-based immunosuppressive regimen. CsA and tacrolimus dosages were adjusted to trough levels of 150-250 ng ml-1 (EMIT) and 5-15 ng ml-1 (MEIA II) respectively. Three patients died from sepsis due to Aspergillus fumigatus infection. Reasons for a fatal outcome were foudroyant Aspergillus pneumonia in a patient transplanted for fulminant hepatic failure on post-operative day (pod) 8; Aspergillus sepsis with severe endocardidtis in a patient with two retransplantations for graft non/dysfunction on pod 24; and disseminated aspergillosis due to Aspergillus fumigatus in a patient retransplanted for primary non-function (pod 19). All three patients underwent haemofiltration for renal failure. One patient with Candida albicans sepsis (pod 4) recovered under increased dosage of Ambisome (3 mg kg-1 per day). Ambisome (1 mg kg-1 per day) seems to be beneficial against systemic Candida infections. However, the onset of systemic Aspergillus infections could not be prevented. Obviously, higher Ambisome doses appear to be necessary against Aspergillus. We recommend the use of Ambisome (3 mg kg-1 per day) for patients with risk factors such as graft dys-/non-function, retransplantation, haemofiltration and complicated acute liver failure to prevent invasive aspergillosis.

AspergillusInfections in Transplant Recipients

“…Low doses (1 mg/kg/day) of lipid formulations of amphotericin B have also not been effective in case series (171,321). Breakthrough infections were documented in 5% of the patients in one study (171) and in 10% in another (321) in which Ambisome at 1 mg/kg/day was used.…”

“…Low doses (1 mg/kg/day) of lipid formulations of amphotericin B have also not been effective in case series (171,321). Breakthrough infections were documented in 5% of the patients in one study (171) and in 10% in another (321) in which Ambisome at 1 mg/kg/day was used. A lack of cases of invasive aspergillosis precluded meaningful assessment of the efficacy of 1 mg of liposomal amphotericin B (Ambisome)/kg/day as prophylaxis against Aspergillus infections in a randomized trial (315).…”

Antifungal Prophylaxis in Solid-Organ Transplant Recipients: Considerations for Clinical Trial Design

“…Low-dose amphotericin B not only was ineffective but, in fact, increased the risk of invasive aspergillosis after liver transplantation [30]. Likewise, low doses of lipid formulations of amphotericin B (1 mg/kg/day) have not been shown to be effective [31,32]. Concerns regarding poor bioavailability and absorption in the immediate posttransplantation period dissuade from the use of itraconazole as a potential candidate for prophylactic studies among transplant recipients.…”

Prophylactic Use of Liposomal Amphotericin B in Preventing Fungal Infections Early After Liver Transplantation: A Retrospective, Single-Center Study

“…Also, the majority of the available studies were published more than a decade ago. The study by Mora et al [10] used conventional amphotericin B in a dose of 1 mg/kg during 5 days; the study by Braun et al [11] used different doses of L-AmB, from 1 to 5 mg/kg until the discharge from the ICU); Lorf et al [12] used a dose of 5 mg/kg/day of LAmB for 7 days; Castroagudin et al [13] used a dose of 1 mg/ kg L-AmB for 7 to 10 days. Nonetheless, all these studies concluded that this prophylaxis is effective in high-risk groups.…”