Antifungal Prophylaxis in Lung Transplant Recipients

Abstract

Invasive fungal infection remains a serious postoperative complication in lung transplant recipients and is associated with significant morbidity and mortality. Although most lung transplant centers use antifungal prophylaxis, consensus on the strategy, choice of antifungal agent(s), route of administration, and duration of prophylaxis have not been established. This review provides an overview of the epidemiology and risk factors for common fungal infections seen in lung transplant recipients, evaluates the clinical efficacy and toxicity of the various antifungal agents used to prevent infection, and offers recommendations and opportunities for future research. Currently available data evaluating the efficacy of antifungal prophylaxis strategies is limited by a lack of prospective, randomized clinical trial data and variability in patient populations, prophylactic and immunosuppressive strategies, dosing, durations of use of antifungal agents, and definitions of invasive infection. There is controversy regarding significant risk factors for invasive fungal infection, which has limited the development and validation of targeted prophylactic strategies. Inhaled formulations of amphotericin B remain the most widely studied option for universal prophylaxis and have been shown to be effective in reducing the incidence of invasive Aspergillosis as compared with no prophylaxis. Concern over early postoperative extrapulmonary infection may suggest a benefit of initial prophylaxis with a systemic azole. Long-term use of systemic antifungals is not optimal due to emerging evidence of long-term toxicities. Multicenter, randomized trials are needed to ascertain the optimal prophylactic strategy in lung transplant recipients. New agents and delivery mechanisms may offer additional opportunities for comparative research.

Infectious Complications in Lung Transplant Recipients

“…can manifest in a variety of ways, ranging from airway colonization to tracheobronchitis to life-threatening lower respiratory tract infections. Currently, the optimal strategy for Aspergillus prophylaxis has yet to be defined and there is variability among transplant centers regarding choice of therapy and duration [9,52]. Systemic administration of an azole such as voriconazole is a widely used approach to reduce rates of IA among lung transplant recipients, but its use may be limited by drug interactions and hepatotoxicity [52,53].…”

Population Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung Transplantation

“…Fungal infection is associated with high morbidity and mortality rates in patients following lung transplantation (LTx) ( 1 – 3 ). Antifungal prophylaxis in lung transplant recipients may reduce the incidence of fungal infections and the risk of death ( 4 ). However, there is no optimized method for the prophylaxis of fungal infection after lung transplantation that is commonly accepted.…”

Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients

“…Broad-spectrum triazole antifungal agents have improved the outcomes of SOT recipients by offering safe and effective alternatives to the more toxic agent amphotericin B for treating IFIs, in particular invasive mold infections like aspergillosis and mucormycosis. These agents are also employed for prophylaxis by many SOT programs (6). Isavuconazole (ISA) is a triazole agent that was recently approved by the Food and Drug Administration and the European Medicines Agency, which offers potential pharmacokinetic (PK) advantages over other triazoles like voriconazole or posaconazole (POS).…”