Background. Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapyinduced 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 ≥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-totreat 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.,
Clinical Infectious Diseases
Erasmus MC: University Medical Center Rotterdam

Rijnders, B., Cornelissen, J., Slobbe, L., Becker, M., Doorduijn, J., Hop, W., … de Marie, S. (2008). Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: A randomized, placebo-controlled trial. Clinical Infectious Diseases, 46(9), 1401–1408. doi:10.1086/586739