Combined Short Term Caspofungin and Nebulized Amphotericin B Prophylaxis May Help To Eradicate Aspergillus Related Complications After Lung Transplantation

Early treatment strategies in our institute resulted 10% invasive Aspergillus (IA) mortality within the first posttransplant year. Despite the incidence of IA is lower nowadays, a wide variety of related complications, like posttransplant tracheobronchitis, anastomotic and airway complications requiring interventions, invasive pulmonary disease, fistulas, surgical site infections, endocarditis and systemic spread of IA are reported. The aim of this retrospective study was to evaluate the outcomes of a combined systemic caspofungin and nebulized Amphotericin B (nAmB) prophylaxis. We followed 96 consecutive double lung transplant patients operated on between 2007-12. This series include 7 re- or re-re-transplantations and 13 patients bridged to transplantation using ECMO. With few exceptions, routine antifungal prophylaxis consisted of caspofungin 50 mg iv. at induction and second dose 24 hours later. nAmB was started immediately in ICU, and nAmphoricin B lipid complex was continued once a week until re-epithelisation of the bronchial anastomosis was complete. The endpoints were postoperative Aspergillus colonization or disease or death due to any cause, or airway complication requiring intervention. The respective 30 day and 1 year survivals were 99% and 97%. The antifungal prophylactic regimens were safe and well tolerated. 93% of patients were alive at the end of the follow up (aver. 3.0 years). No clinically confirmed IA infections occurred. Postoperative colonization was rare. No airway complications requiring dilatation or stents were detected. Preoperative Aspergillus colonization/disease was not a risk factor for death. This is the first report of Aspergillus prophylaxis using the combination of caspofungin and nebulized Amphotericin B. This prophylaxis was associated with a very low number of complications. The correct timing, systemic coverage, synergistic effect and minimal toxicity of the prophylaxis are considered highly important. The effect of surgical techniques, tailored immunosuppression and postoperative colonization in regards to development of BOS will be discussed.