Myers S E, Devine S M, Topper R L, Ondrey M, Chandler C, O'Toole K, Williams S F, Larson R A, Geller R B
University of Chicago Medical Center, Department of Medicine, Illinois 60637.
Leuk Lymphoma. 1992 Oct;8(3):229-33. doi: 10.3109/10428199209054909.
Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.
侵袭性曲霉病仍然是长期中性粒细胞减少患者发病和死亡的重要原因。我们进行了一项I期试验，使用带有一次性细菌呼气过滤器的面罩雾化器系统，递增剂量雾化两性霉素B。将5、10、15和20毫克药物溶解在无菌水中，每天两次，在10至15分钟内吸入。对26名患者（18名移植受者和8名白血病患者）进行了耐受性研究。在任何剂量水平均未观察到副作用。14名患者（54%）在因发热开始经验性使用静脉注射（IV）两性霉素B进行抗真菌治疗时停止了预防性治疗。11名患者（43%）继续吸入两性霉素B，直到血细胞计数恢复。一名患者在出现心源性肺水肿后退出研究。没有患者发生临床可疑或病理记录的侵袭性曲霉病感染。预防性雾化两性霉素B在每日两次5、10、15和20毫克的剂量下耐受性良好。此外，预防性雾化两性霉素B似乎不会使患者对随后使用的静脉注射两性霉素B产生敏感性。尽管这项研究表明预防性吸入两性霉素B耐受性良好且有效，但仍需要进行大规模对照试验。
