Breakthrough Invasive Fungal Infections (bIFI) in Adult Patients with Leukemia Receiving Isavuconazole (ISA). (4th October 2017)

• Record Type: Journal Article
• Authors: Rausch, Caitlin R; Dipippo, Adam J; Kontoyiannis, Dimitrios P
• Is Part Of: Open forum infectious diseases. Volume 4(2017)Supplement 1
• Page Start: S718
• Page End: S718
• Publication Date: 2017-10-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx163.1931
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: ISA is a new broad-spectrum triazole antifungal for the treatment of IFIs. As the drug has both oral and intravenous formulations, the ability to be administered once-daily, a favorable pharmacokinetic profile, and good tolerability, it has being increasingly used. ISA may be considered as prophylaxis, combination, or salvage therapy for primary treatment for a vast variety of IFIs. Limited data exists on the incidence and pattern of bIFI in leukemia patients receiving ISA. Methods: We retrospectively reviewed the records of all adult patients with leukemia who received >7 days of 200 mg of ISA (intravenous or oral) or >5 days of 200 mg of ISA following a loading dose (200 mg every 8 hours for 48 hours) while hospitalized between March 2015 and December 2016. bIFI was defined according to EORTC/MSG. Results: Thirty-nine patients received ISA for treatment of suspected IFI (77%) or as prophylaxis (23%). Three patients (8%) did not receive a loading dose. 70% of patients had acute myeloid leukemia; 82% relapsed/refractory disease. At the time of ISA initiation, 64% were neutropenic. Eighty-one percent of neutropenic patients had a duration of neutropenia >14 days at the time of initiating ISA. Eight (21%) patients had bIFI (1 definite, 3 probable, 4 possible) while receiving continuous ISA. All but one ( C. parapsilosis fungemia) patient with bIFI had pneumonia. Probable bIFI pneumonias included 1 due to Rhizomucor spp., 1 Rhizopus spp. and 1 with BAL + for Aspergillus GM. bIFI occurred after a median of 111 days of therapy (range 29–338). At the time of bIFI, 38% of patients were profoundly neutropenic (ANC<100). ISA was well tolerated, only 1 patient discontinued therapy due to potential toxicity. Conclusion: Twenty-one percent of leukemia patients developed bIFI, typically pneumonia, while receiving ISA and 2 of bIFI were pneumonias due to Mucorales. These bIFIs were frequently observed late in ISA treatment and in the setting of profound neutropenia and active leukemia. Disclosures: D. P. Kontoyiannis, Pfizer: Research Contractor, Research support and Speaker honorarium. Astellas: Research Contractor, Research support and Speaker honorarium. Merck: Honorarium, Speaker honorarium. Cidara: Honorarium, Speaker honorarium. Amplyx: Honorarium, Speaker honorarium. F2G: Honorarium, Speaker honorarium