Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients

Abstract

To determine the value of aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis (IPA), we initiated a prospective randomized multicenter trial. The scheduled intent-to-treat interim analysis included 115 patients (30%) with prolonged neutropenia after chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia/high-grade non-Hodgkin's lymphoma, or solid tumors undergoing autologous stem cell transplantation. Sixty-five patients had been randomized to receive prophylactic aerosol amphotericin B inhalations at a dose of 10 mg twice daily (group A); for the remaining 50 patients no aerosol amphotericin B prophylaxis was used (group B). No serious side effects from amphotericin B inhalations occurred, but coughing (54%), bad taste (51%), and nausea (37%) caused early cessation of aerosol amphotericin B prophylaxis in 23% (15/65) of courses. In group A, the incidence of proven, probably, or possible IPA was 5% (3/65) as compared with 12% (6/50) in group B (p > 0.05). Microbiologically documented bacterial pneumonias were observed in 5/65 (8%) patients in group A and in 1/50 (2%) patients in group B (p > 0.05). Thus, no reduction in incidence of IPA from use of prophylactic aerosol amphotericin B inhalations was found in this interim analysis. As there were no serious side effects from aerosol amphotericin B prophylaxis, accrual in the study will continue for a total of 380 patients.

AspergillusInfections in Transplant Recipients

“…Aerosolization of amphotericin B has been shown to be effective in some but not other reports on hematopoietic stem cell transplant recipients (21,59,103,281). The findings and the conclusions based on these studies, however, are difficult to generalize given the variability in the dose, frequency of administration, mode of delivery, and concomitant use of other antifungal prophylaxis and a low number of cases of documented infections.…”

Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: Before and after chemoprophylaxis and institution of HEPA filters

“…The median length of neutropenia was 18 days (range 5-33). Eighteen of 28 patients had AML with a median neutropenic length of 20 days (range 5-33), and 10/18 patients had ALL with a median neutropenic period of 13 days (range [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

“…Group 3-a consisted of 37 AML patients with median length of neutropenia of 16 days (range 5-120), and 8 ALL patients with median of 17 days (range 7-40) of neutropenia. Group 3-b consisted of 23 AML patients with median neutropenia duration of 15 days (range 5-42), and 3 ALL patients with median neutropenia duration of 11 days (range [8][9][10][11][12][13][14][15][16][17][18][19][20]. In group 3-c 26 patients underwent allogeneic BMT in the hematology ward with a median neutropenic period of 15 days (range 9-26), and 168 patients underwent autologous BMT in the hematology ward with median neutropenic period of 10 days (range 7-25).…”

“…low-dose Amphotericin B (AB) [13][14][15], AB inhalations [16,17], intranasal AB [18,19], or Itraconazole [19], all showed variable success.…”

Practical modalities for prevention of fungal infections in cancer patients

“…Moreover, the incidence of disseminated aspergillosis was consid erably higher at participating centers before the trial than that reported in other surveys ( Figure 3 ). However, a subsequent prospective, randomized study showed that the aerosol amphotericin B of fered no statistically significant advantage with re spect to the number of documented infections or overall survival (26). In fact, more cases of bacte remia were documented (26) in patients who in haled nebulized amphotericin B.Thus, until further investigations are undertaken, no firm conclu sions as to the efficacy of this strategy can be drawn.…”