title: Fatal outcome of disseminated candidosis after allogeneic bone marrow transplantation under treatment with liposomal and conventional amphotericin-B. A report of 4 cases with determination of the Mic values.
abstract: Four patients undergoing allogeneic bone marrow transplantation were treated with liposomal (3 patients) and conventional (one patient) amphotericin-B for disseminated candidosis. Candida krusei was isolated from 3, and C. glabrata from 1 patient. The patients were treated with liposomal amphotericin-B in doses from 3 to 5 mg/kg. The fourth patient received conventional amphotericin-B in a reduced dose due to renal impairment. The patients died from multiorgan failure due to disseminated fungal infection. In 1 case, the switch to the conventional drug resulted in clearance before death. The 3 fungus isolates, together with the fourth strain obtained from patient no. 4 without any exposition to liposomal amphotericin-B were tested for their susceptibility to conventional, liposomal and discoidal amphotericin-B. All strains showed good sensitivity to the conventional and discoidal drug. The minimal inhibitory concentrations (MIC) of liposomal amphotericin-B were 1 to 3 titre steps higher indicating a reduced sensitivity of the tested strains to this preparation. We conclude that the use of liposomal amphotericin-B is recommended mainly on the base of the low incidence of side-effects. Intensive microbial resistance tests, pharmacokinetic investigations and randomized studies are necessary before the conventional drug is replaced as the gold standard for systemic antimycotic therapy.
authors.affiliation: Department of Oncology/Haematology, University-Hospital Eppendorf, Hamburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Krüger
authors.forename: I
authors.initials: I
authors.lastname: Sobottka
authors.forename: M
authors.initials: M
authors.lastname: Stockschläder
authors.forename: K
authors.initials: K
authors.lastname: Mross
authors.forename: M
authors.initials: M
authors.lastname: Hoffknecht
authors.forename: B
authors.initials: B
authors.lastname: Rüssmann
authors.forename: M
authors.initials: M
authors.lastname: Horstmann
authors.forename: R
authors.initials: R
authors.lastname: Betker
authors.forename: A
authors.initials: A
authors.lastname: Zander
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality*; D004337:Drug Carriers; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008826:Microbial Sensitivity Tests; D051437:Renal Insufficiency / Q000150:complications; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B