title: Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B.
abstract: We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.
authors.affiliation: UZ Gent, Ghent, Belgium.
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
authors.forename: Vladimir
authors.initials: V
authors.lastname: Krcmery
authors.forename: Marc
authors.initials: M
authors.lastname: Boogaerts
authors.forename: Chantal
authors.initials: C
authors.lastname: Doyen
authors.forename: Dan
authors.initials: D
authors.lastname: Engelhard
authors.forename: Patricia
authors.initials: P
authors.lastname: Ribaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Cordonnier
authors.forename: Ben
authors.initials: B
authors.lastname: de Pauw
authors.forename: Simon
authors.initials: S
authors.lastname: Durrant
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marie
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Harry
authors.initials: H
authors.lastname: Guiot
authors.forename: George
authors.initials: G
authors.lastname: Samonis
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D002423:Cause of Death; D002648:Child; D025141:Drug Resistance, Fungal; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications; D009761:Nystatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D013534:Survival; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D008081:Liposomes; D009761:Nystatin; D000666:Amphotericin B