Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia

Abstract

The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneic n = 271, autologous n = 27, syngeneic n = 5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.

Addition of aerosolized deoxycholate amphotericin B to systemic prophylaxis to prevent airways invasive fungal infections in allogeneic hematopoietic SCT: a single-center retrospective study

“…In 40 patients undergoing allogeneic HSCT, aerosolized lipid complex (50 mg once daily for 4 days, thereafter once weekly for 13 weeks) was well tolerated and only one proven IFI was reported during the study period. 8 In a large retrospective study 9 10 mg of d-AmB was delivered twice daily during neutropenia in HSCT patients: in this cohort of patients a low cumulative incidence of IFIs was observed (3.6% at 120 days after transplant). In a more recent randomized controlled trial, 25 mg once daily of liposomal amphotericin B administered for 2 days weekly until neutrophil recovery was randomly compared with placebo in 271 patients during 407 episodes of prolonged neutropenia.…”

“…Recent studies suggest that aerosolized lipidic formulations of amphotericin B could be effective in preventing airways IFIs in lung 7 and HSCT 8,9 and during prolonged neutropenia. 10 In lung transplant recipient, 50 mg of lipid complex amphotericin B was compared with 25 mg once daily of deoxycholate-amphotericin B inhalations: 7 in each arm full-dose treatment was delivered for 1 week followed by one inhalation weekly for 7 weeks.…”

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

“…63,64 The only large multicenter trial did not confirm these results (Level E I). 65 In a non-comparative evaluation of inhalational amphotericin B lipid complex 50 mg/d and concomitant fluconazole 400 mg/d were found to be safe in allogeneic stem cell recipients.…”

Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group

“…28 Aerosolized amphotericin B, suggested to be useful for prophylaxis, was not confirmed as effective in a randomized evaluation. 29,30 A recent study using 2 mg/kg/day of liposomal amphotericin three times a week demonstrated little toxicity, but did not show a significant reduction in fungal infections. 31 Three large-scale series have compared Fluconazole and oral placebo, either in patients with acute leukemia or those undergoing bone marrow transplantation.…”