Breakthrough Mucormycosis Developing on Mucorales-Active Antifungals Portrays a Poor Prognosis in Patients with Hematologic Cancer
Dierdre B. Axell‐House, Sebastian Wurster, Ying Jiang, Andreas Kyvernitakis, Russell E. Lewis, Jeffrey J. Tarrand, Issam Raad, Dimitrios P. Kontoyiannis
Abstract
Although breakthrough mucormycosis (BT-MCR) is known to develop on mold-active antifungals without Mucorales activity, it can also occur while on Mucorales-active antifungals. Herein, we retrospectively compared the characteristics and outcomes of patients with hematologic malignancies (HMs) or hematopoietic stem cell transplant (HSCT) who developed BT-MCR on mold-active antifungals with or without Mucorales activity. Of the patients developing BT-MCR, 16 were on Mucorales-active antifungals (9 isavuconazole, 6 posaconazole, 1 amphotericin B), and 87 were on other mold-active agents (52 voriconazole, 22 echinocandins, 8 itraconazole, 5 echinocandin + voriconazole). Both groups were largely comparable in clinical characteristics. Patients developing BT-MCR while on Mucorales-active antifungals had higher 42-day mortality, from either symptom onset (63% versus 25%, p = 0.006) or treatment initiation (69% versus 39%, p = 0.028). In multivariate Cox regression analysis, exposure to Mucorales-active antifungals prior to BT-MCR had a hazard ratio of 2.40 (p = 0.015) for 42-day mortality from treatment initiation and 4.63 (p < 0.001) for 42-day mortality from symptom onset. Intensive care unit (ICU) admission and APACHE II score at diagnosis, non-recovered severe neutropenia, active HM, and amphotericin B/caspofungin combination treatment were additional independent predictors of 42-day mortality. In summary, BT-MCR on Mucorales-active antifungals portrays poor prognosis in HM/HSCT patients. Moreover, improvements in early diagnosis and treatment are urgently needed in these patients.