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Systemic mycoses during prophylactical use of liposomal amphotericin B (Ambisome) after liver transplantation
1Klinik für Transplantationschirurgie, Georg-August-Universität, Göttingen, Germany.
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.
Insights
Liposomal amphotericin B (Ambisome) prophylaxis after liver transplantation (LTx) effectively treated Candida infections. However, higher Ambisome doses are needed to prevent invasive Aspergillus infections in high-risk LTx patients.
Area of Science:
- Mycology
- Transplantation Medicine
- Pharmacology
Background:
- Liver transplantation (LTx) patients are susceptible to invasive fungal infections.
- Prophylactic antifungal strategies are crucial in the early post-transplant period.
- Liposomal amphotericin B (Ambisome) is a potential agent for fungal prophylaxis.
Observation:
- Fifty-eight patients received prophylactic Ambisome (1 mg/kg/day) for 7 days post-LTx.
- Immunosuppression involved cyclosporine A or tacrolimus.
- Three patients died from invasive Aspergillus fumigatus infections, often in those with graft complications or renal failure requiring hemofiltration.
- One patient with Candida albicans sepsis recovered with an increased Ambisome dose (3 mg/kg/day).
Findings:
- Prophylactic Ambisome at 1 mg/kg/day was effective against systemic Candida infections.
- The same dose did not prevent invasive Aspergillus infections.
- Higher Ambisome doses (3 mg/kg/day) may be necessary for Aspergillus prophylaxis.
Implications:
- Ambisome (1 mg/kg/day) shows benefit for Candida prophylaxis in liver transplant recipients.
- Higher Ambisome doses (3 mg/kg/day) are recommended for high-risk patients (graft dysfunction, retransplantation, renal failure) to prevent invasive aspergillosis.
- Further studies are warranted to optimize Ambisome dosing for invasive aspergillosis prevention in LTx.