title: Liposomal amphotericin B (AmBisome) for fungal infections in immunocompromised adults and children.
abstract: Invasive fungal infections are rare but life-threatening infections, most often occurring in immunocompromised patients. For a long time, Amphotericin B has been the best choice for treatment, because it is fungicidal with a broad antifungal spectrum and minimal risk of resistance development. The therapeutic use of amphotericin B has, however, been limited by its toxicity-both acute as well as chronic. To counter this, amphotericin B has been encapsulated in liposomes, which reduces its toxicity and allows higher doses to be given. Ambisome is a true, spherical, small unilamellar liposome with a median size of 80 nm. The pharmacokinetic profile was changed, and the maximum concentration and AUC of amphotericin B after AmBisome treatment were greater than those found with the conventional drug. The highest tissue concentrations of AmBisome were found in the liver and spleen, and less than 1% of the administered dose was recovered in other organs. At Huddinge University Hospital, we were the first to use and report on the experience of AmBisome. We now have more than 12 years' experience in transplant recipients, with a good safety profile, improved rate of curing mycological proven infections and reduced mortality in fungal infections. In two placebo-controlled prophylactic trials, we found that AmBisome was effective for preventing fungal colonization and invasive fungal infections, respectively, in allogeneic stem cell and liver transplantation. In uncontrolled and, more recently, in randomized controlled studies at other centers, AmBisome has revealed less toxicity and an efficacy equal or superior to that of the conventional drug in treating neutropenia-associated fever and proven invasive fungal infections in both adults as well as in children. Although investigators tend to increase the dose used, the optimal dose for probable or proven infection is still under debate. Based on our own experience in using AmBisome and the experience at other centers, we can conclude that AmBisome represents a major breakthrough in the treatment of invasive fungal infections, especially in immunocompromised patients.
authors.affiliation: Department of Transplantation Surgery, Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. Jan.Tollemar@transpl.hs.sll.se
authors.forename: J
authors.initials: J
authors.lastname: Tollemar
authors.forename: L
authors.initials: L
authors.lastname: Klingspor
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D002648:Child; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007231:Infant, Newborn; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000517:prevention & control*; D008081:Liposomes; D008297:Male; D009181:Mycoses / Q000188:drug therapy / Q000517:prevention & control*; D009894:Opportunistic Infections / Q000188:drug therapy / Q000517:prevention & control*; D014018:Tissue Distribution; D014180:Transplantation / Q000009:adverse effects
chemical_list: D000935:Antifungal Agents; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B