Experience with Posaconazole Use for Fungal Prophylaxis Immediately Post Heart Transplant

Abstract

Purpose Fungal infections, specifically mucormycosis, are associated with high morbidity and mortality in the immunocompromised host. Noting a recent elevation in our rates of fungal infections, we sought to avoid mucormycosis and other post-Orthotopic Heart Transplant (OHT) fungal infections through the implementation of a systematic antifungal prophylaxis protocol. Methods Posaconazole was selected as the antifungal of choice, given provided mucormycosis coverage not provided by other azoles. We developed a Posaconazole Prophylaxis Protocol (PPP) consisting of post-operative day 1 initiation of posaconazole for a 3-month duration with a goal posaconazole trough level 1000-2000 ng/mL. At time of posaconazole discontinuation, a 2-fold dose escalation of tacrolimus dosing was implemented and bi-weekly tacrolimus levels drawn for 2 weeks to ensure goal calcineurin inhibitor levels. If strong cyp3A4 interactions or prolonged QTc prohibited posaconazole, isavuconazole was used. If early cessation of posaconazole-therapy was necessary, surveillance chest imaging was obtained with chest CT scans. Results In the 13-month period following initiation of our PPP 50 patients underwent OHT. All but one (49/50) patients received therapeutic posaconazole or in the case of drug-drug interactions, isavuconazole. 2/50 were transitioned to isavuconazole due to QT prolongation. 5/50 had posaconazole interruption with the most common reason being liver enzyme elevation (4/50). 45/50 tolerated the 3-month period on systemic azole prophylaxis. During this period there were no systemic fungal infections. Conclusion Our initial 13-month experience with a systematic 3-month antifungal prophylaxis protocol appears to be feasible, safe, and associated with uniform prevention of mucormycosis and other fungal infections that have previously proven to be highly morbid in our OHT recipients.