A Multi-Institution Retrospective Case Report Analysis of Emergence of Breakthrough Zygomycoses in Patients on Prior Voriconazole Therapy.

Background: The incidence of Zygomycete infection has been increasing, almost exclusively in patients with hematologic malignancy with or without history of stem cell transplantation. In a single institution case control study, voriconazole was identified as an independent risk factor for the development of Zygomycete infections. A small number of single institution case reports have also been noted.

Methods: Investigators for The Research on Adverse Drug Events and Reports (RADAR) project requested collaboration from cancer centers regarding the identification and characterization of Zygomycete infections in patients with prior exposure to voriconazole. 12 centers participated in this study project. Medical records were reviewed and data collected on a standard case report form including diagnosis, transplant type, concomitant risk factors, exposure times, concurrent infection and outcomes. A minimum of 5 days exposure was noted between clinical diagnosis and confirmation with either tissue or histology.

Results: 54 cases were identified from 12 centers and with notably almost 75% mortality rate in individuals who were diagnosed with Zygomycoses with prior exposure to voriconazole.Of interest 31/54 cases received voriconazole for prophylaxis. Presenting characteristics were similar to those reported previously with lung as major site of infection. Concomitant risk factors included steroid use, immunosupression, GVH, neutropenia and diabetes. Simultaneous co-infections from diverse bacterial, viral and fungal infections were noted in 60% of patients signifying a compromised immune status. Drug therapy with an amphotericin product used to treat the identified Zygomycosis was highly ineffective with failure in 26/32 patients with resultant mortality.

Conclusion: Rates of breakthrough zygomycoses with high mortality rates with prior voriconazole therapy are on the increase. Appropriateness of prophylactic use as well as early diagnosis and institution of antifungal therapy in these patients with Zygomycoses is essential to combat this devastating infection.