738. Potent In Vitro activity of Rezafungin (RZF) Against Aspergillus Clinical Isolates Recovered From Lung Transplant Patients Who Have Received ≥3 Months of Triazole Prophylaxis

BACKGROUND: Emergence of azole resistance globally among Aspergillus species has major one health implications for humans and agriculture. At our center, isavuconazole (ISA), posaconazole (POS) and voriconazole (VOR) have been used as antifungal prophylaxis for at least 3 months or as pre-emptive therapy in solid-organ transplant (SOT) patients. We previously showed that azole breakthrough (BT) fungi were more likely to be non-fumigatus Aspergillus (non-Af) spp. In addition, azole BT isolates exhibited higher azole MICs than non-BT isolates, with 7% pan-azole resistance. RZF is an investigational echinocandin with long serum half-life, suitable for prolonged dosing intervals. We determined caspofungin (CAS) and RZF minimum effective concentrations (MECs) against Aspergillus isolates from our center. METHODS: Aspergillus recovered from 111 patients between December 2016 and April 2018 were tested. MICs (minimum inhibitory concentrations; azoles) and MECs (echinocandins) were measured. Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258 were used as QC controls. RESULTS: 71% (79) of isolates were from SOT patients. Aspergillus spp. were A. fumigatus (Af, 73), A. flavus (Afl, 12), A. niger (An, 9), A. terreus (At, 8), A. calidoustus (Ac, 7), and A. lentulus (Al), A. glaucus, A. thermomutatus, and A. thermomutatus (At; 1 each). 7% of Aspergillus isolates exhibited VOR, POS and ISA MICs ≥2, ≥8 and ≥1 µg/mL, respectively. RZF MEC(50) and range of MEC by Aspergillus spp.are summarized in the Table. Overall, there was no difference in MECs between CAS and RZF (P = 0.21). 6% (7) and 7% (8) of the non-Af isolates exhibited CAS and RZF MECs >0.5 µg/mL, respectively. 5 isolates exhibited CAS and RZF MEC ≥16 µg/mL. CONCLUSION: Despite concerns over azole resistance among Aspergillus, these agents remain frontline against invasive aspergillosis. The excellent activity of RZF and CAS shown here suggests that the drugs are potential therapeutic options for patients infected with azole BT Aspergillus, including azole-resistant isolates. The long-half-life and high tolerability of RZF make this agent an attractive consideration for antifungal prophylaxis. A clinical trial of RZF prophylaxis in stem cell transplant recipients is planned. [Image: see text] DISCLOSURES: All authors: No reported disclosures.