Amphotericin B lipid complex in the treatment of invasive fungal infections in liver transplant patients

Abstract

F UNGAL infections continue to be a major source of morbidity and mortality following liver transplantation (LTx). Infection rates have been reported to bc as high as X3.8%,’ with an associated mortality of up to 500/r.‘.” Liver disease and the transplant procedure itself have inherent risks that increase the likelihood for fungal infection. These include portal occlusion and hypertension, hypoalbuminemia, bowel edema. immunosuppression. and wide disscction.’ ’ In addition. several risk factors have been identified that further increase the risk for fungal infection. Among these risks are the patient’s preoperative status. lengthy operations, transfusion requirement, Roux-Y biliary reconstruction, retransplantation, reoperations, and bacterial infcctions.’ -’ Amphotericin B (AmB) has been the main pharmaccutical agent used in the treatment of invasive mycoscs owing to its wide spectrum and fungicidal activity. Its USC, howcvcr, is limited by its narrow therapeutic index. Its renal toxicity is particularly disturbing, especially when given with other nephrotoxic drugs, which most transplant patients require for immunosuppression. In addition, certain organisms. eg, Aspqihs species, have been resistant to AmB treatment in vivo despite demonstrated sensitivity in vitro. This may be due to inadequate availability of the drug at the site of infection. Amphotcricin B lipid complex (ABLC) was designed to increase the etficacy of AmB while simultaneously decreasing its toxicity. ABLC is a lipid complex consisting of AmB and lipid in a l-to-l molar ratio. The lipids arc dimyristoylphosphatidycholine (DMPC) and dimyristoylphosphatidyglyccrol (DMPG) in a 7-to-3 ratio. The complex itself has been found to interact minimally with mammalian cells. possibly explaining its reduced toxicity. At the site of infection, howcvcr, lipases, relcascd by either the fungi or macrophages and ncutrophils. break down the complex and release the active drug.” Our objective was to test the eticacy and safety of ABLC in the treatment of fungal infections in LTx patients. ABLC was made available to 13 patients on a compassionate use basis for the treatment of 15 episodes of fungal infection.