Solid organ transplant (SOT) recipients are at increased risk of developing severe disseminated endemic fungal infections (EFI). Guidelines recommend prolonged antifungal therapy in the setting of chronic immunosuppression, but there is no evidence to support this approach. While a limited treatment course reduces the risk of drug interactions related to CYP3A4 inhibition, prolonged azole therapy may prevent reactivation of EFI. A single-center, retrospective study assessed the efficacy and safety of chronic suppressive azole therapy for SOT recipients with EFI.
A retrospective analysis was conducted on SOT recipients diagnosed with EFI between 1 January 2005 and 31 December 2014 and treated with azole therapy for more than a year as of 1 January 2016. Safety endpoints included adverse reactions and drug interactions. Efficacy was defined as preventing EFI reactivation.
Using microbiology and billing records, we identified 15 SOT recipients (7 kidney, 3 kidney-pancreas, 3 heart, 2 liver) diagnosed with EFI who were treated with chronic suppressive azole therapy (Figure 1). A total of 7 histoplasmosis, 5 blastomycosis, and 3 coccidioidomycosis infections were identified. Disseminated infection occurred in 7 (47%) patients. The median length of azole therapy was 6 years (range 2-10). Three (20%) patients experienced an adverse reaction to itraconazole (level range 0-1.6 mcg/mL). Symptoms included nausea, vomiting, and lower extremity edema. Adverse reactions occurred within 3 months of starting itraconazole and patients were transitioned to another azole with minimal side effects. There was one adverse drug interaction; itraconazole was discontinued after 4 years of treatment in a patient with asymptomatic bradycardia on amiodarone. Allograft rejection occurred in 4 patients. There were no episodes of EFI reactivation.
Chronic suppressive azole therapy was safe and effective among SOT recipients. Most adverse reactions occurred when azole therapy was initiated; otherwise, prolonged treatment was well tolerated. All patients with adverse reactions were successfully transitioned to an azole with minimal side effects. Prolonged azole therapy can effectively treat and prevent EFI.
S. Penugonda, None
I. Echenique, None