Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Microbiology, BRONCHOALVEOLAR LAVAGE FLUID, FUNGAL-INFECTIONS, ANTIFUNGAL PROPHYLAXIS, GALACTOMANNAN, DEOXYCHOLATE, FLUCONAZOLE, THERAPY, POSACONAZOLE, FORMULATIONS, ILOPROST, Administration, Inhalation, Adolescent, Adult, Aged, Amphotericin B, Antifungal Agents, Aspergillosis, Female, Humans, Kaplan-Meier Estimate, Lung Diseases, Fungal, Male, Middle Aged, Neutropenia, Treatment Outcome, 06 Biological Sciences, 11 Medical and Health Sciences, 3202 Clinical sciences

Abstract:

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. METHODS: We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for >or=10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations. RESULTS: A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P=.005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02-0.66; P=.007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P=.002). CONCLUSION: In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.