Hit early and hard – successful treatment of invasive pulmonary aspergillosis with the combination of voriconazole and micafungin in heart transplant recipients

Introduction: Invasive aspergillosis is a life-threatening complication in immunocompromised patients with mortality rates between 30 and 90 percent. Due to the sub-optimal outcome of the standard approach with antifungal monotherapy (either azoles or echinocandins) combined antifungal therapy has become a point of interest. Results of in vitro studies, animal models and case reports suggest that antifungal combination therapy with azoles (e.g. voriconazole, posaconazole, ravuconazole) and echinocandins (e.g., caspofungin, micafungin, anidulafungin) may have additive activity against aspergillus species. We present three cases of invasive pulmonary aspergillosis in heart transplant recipients that were successfully treated with a combination of voriconazole and micafungin. Aims: Three heart transplant recipients developed invasive pulmonary aspergillosis ten days, nine and eighteen months after heart transplantation (HTx), respectively. Clinical signs were productive cough and fever. Computed tomography (CT) was performed and showed atypical infiltration. Bronchoscopy and bronchoalveolar lavage confirmed invasive aspergillosis. Medical therapy was started with micafungin (100mg/d intravenously) and voriconazole (initially 400mg/d intravenously, oralized after two days). Immunosuppression (tacrolimus and mycophenolate mofetil or tacrolimus and everolimus) was reduced, in one individual even paused for two days. Before discontinuing dual therapy, CT revealed a marked size reduction of the aspergillomas in all three cases. Fig.1: Aspergillosis before and after treatment Micafungin was given for 10 to14 days, and the patients were discharged with an antifungal maintenance therapy (voriconazole 400mg/day orally for six months). After 1.4 and 6 months, CT findings were merely normalized, and all patients are doing well. Discussion: In such life threatening circumstances, we believe an antifungal combination therapy is justified.