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 I. Raad, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number217
JournalJournal of Fungi
Volume7
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Antifungal therapy
  • Breakthrough mold infection
  • Hematologic malignancy
  • Mortality
  • Mucormycosis

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Plant Science
  • Microbiology (medical)

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