Breakthrough Invasive Fungal Infections in Patients With Hematologic Malignancy (HM) and Hematopoietic Cell Transplantation (HCT) Receiving Isavuconazole for Empiric or Directed Antifungal Therapy

Background. Invasive fungal infection (IFI) is a serious complication in patients undergoing chemotherapy (CT) or HCT for HM. Isavuconazole (ISA) is an important advancement in treating patients suspected to have invasive fungal infection, especially aspergillosis and mucormycosis. The data on breakthrough infections in patients undergoing empiric or specific therapy with ISA is lacking. Methods. All patients with HM and HCT recipients who received >7 days of empiric or specific therapy (for suspected IFI) with ISA were evaluated for breakthrough invasive fungal infections (br-IFI). The cases were identified from microbiology database, and classified as proven or probable per EORTC/MSG definitions. ISA usage was obtained from pharmacy database (between May 2015 and March 2016). Information was collected for: demographics, underlying diagnosis, disease status, HCT or non-HCT, graft versus host disease (GvHD), duration of ISA use prior to diagnosis of br-IFI, and type of fungal organism causing the breakthrough infection. Results. One hundred ninety-seven patients received >1 day of treatment with ISA. One hundred thirty-one patients who received ISA for > 7 days were included in the study. Six of 131 (4.6%) had br-IFI: 1 Candida and 5 Mold. Four of the patients had HCT (all matched unrelated donor – 2 in relapse) and 2 non-HCT (1 with myelodysplastic syndrome and 1 with refractory acute leukemia). The mean duration of treatment with ISA prior to identification of br-IFI was 58 days (range: 18 - 132 days). All patients with br-IFI had therapeutic ISA tough level (range: 1.4 to 4.8). Candida norvegensis was isolated from blood culture in a patient who had HCT: ISA MIC < 0.06. Mold infection in 5 patients: 4 had Aspergillus (1 biopsy proven case and 4 probable), and 1 biopsy proven Rhizopus spp. (after being on ISA for 132 days for treatment of pulmonary aspergillosis). The MIC profile of Rhizopus was: ISA 1.0, posaconazole 2.0, and amphotericin B 2.0. In those with mold br-IFI: 3 had HCT and 2 were non-HCT. Only 1/4 HCT patients had GvHD. Conclusion. Of the ISA treated patients, 4.6% developed br-IFI (yeast and molds) in a group of a very high-risk HM/HCT patients (primarily with relapsed hematologic disorder). Disclosures. All authors: No reported disclosures.