1733. Voriconazole Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplant: How Much Is Enough, Are Low Voriconazole Levels Associated With Opportunistic Infections, and What Are the Reasons for Discontinuation?

BACKGROUND: Patients who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) are at increased risk for invasive fungal infections with associated high morbidity and mortality that necessitates the use of prophylactic antifungals. Voriconazole is commonly used for prophylaxis, but there are no recommendations for therapeutic drug monitoring. The purpose of this study was to characterize voriconazole therapeutic drug monitoring and associated outcomes in this patient population. METHODS: AlloHSCT patients receiving voriconazole prophylaxis at the University of Alabama at Birmingham Hospital between March 2015 and March 2018 were included in the analysis. Serum voriconazole levels (SVL) were evaluated to determine what percentage of patients achieved prophylactic or therapeutic concentrations. Incidence of invasive fungal infections (IFI) and voriconazole discontinuation was also assessed. RESULTS: Voriconazole prophylaxis was used in 151 of 162 alloHSCT patients, and 120 patients (79%) had SVL drawn correctly (≥4 days after initiation of course). We found that 35 (29%) patients achieved a subtherapeutic level (<0.5 μg/mL), 17 (14%) prophylactic level (0.5 to 1 μg/mL), 68 (57%) therapeutic level (1 to 5.5 μg/mL), and no patients achieved a supratherapeutic level (level ≥5.5 μg/mL). Voriconazole prophylaxis was discontinued early in 60 of 151 patients. Most common etiologies for discontinuation included liver function test abnormalities (44%) and encephalopathy (21%). The average SVL was 1.2 μg/mL in those requiring discontinuation. Four patients (3%) developed an IFI while receiving prophylactic voriconazole, of which only 1 had subtherapeutic level. CONCLUSION: Even though approximately one-third of patients achieved a subtherapeutic SVL, there was no correlation with breakthrough IFI. There was also no linear correlation between SVL and risk of adverse effects requiring discontinuation. Our observational data do not support a need for therapeutic drug monitoring in alloHSCT patients receiving prophylactic voriconazole. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.