Poor outcome associated with mucormycosis in critically ill hematological patients: results of a multicenter study

Mucormycosis is an emerging fungal infection that may lead to multi-organ failure, especially in patients with hematological malignancies (HM). We performed a retrospective, cohort study, in five intensive care units (ICU) to assess the outcome of critically ill patients with HM and mucormycosis between 2002 and 2018. The secondary objective was to identify prognostic factors in this setting.

Twenty-six patients were included with a median age of 38 years [IQR, 26-57]). Acute leukemia was the most frequent underlying disease (50%). Nine patients (35%) underwent allogeneic stem cell transplantation (SCT). Nineteen patients (73%) had neutropenia and 16 (62%) had received steroids. The main reason for admission was acute respiratory failure (n = 14, 54%) followed by shock (n = 5 19%). The median SOFA score at admission was 7 [5-8]. According to EORTC/MSG criteria, mucormycosis was "proven" in 14 patients (54%), "probable" in 5 (19%) and "possible" in 7 (27%) in whom diagnosis was made by qPCR. Rhizopus and Mucor were the most frequent documented species. Seven patients (27%) had concurrent Aspergillus infection. Mucormycosis was diagnosed 1 day [-4 to + 6] after ICU admission. Sixteen patients (62%) had pulmonary involvement and ten (38%) rhino-cerebral involvement. Infection was disseminated in eight patients (31%). Twenty-two patients (85%) were treated with liposomal amphotericin B; 12 (46%) received antifungal combination including posaconazole in 7. Eight patients (31%) underwent curative surgery. Twenty-one patients (81%) required invasive mechanical ventilation (IMV), 18 (69%) vasopressors, and 9 (35%) renal replacement therapy. ICU and hospital mortality rates were 77% and 88%, respectively. The median overall survival was 9 days [3-22]. IMV was strongly associated with ICU mortality (p < 0.001) Three variables were associated with day 90 mortality in a Cox model including allogeneic SCT (HR 4.84 [95% CI 1.64-14.32]), SOFA score (1.19 [1.02-1.39]) and dual therapy (3.02 [1.18-7.72]).

Mucormycosis is associated with a high mortality rate in patients with HM, especially in allogeneic SCT recipients. Benefit of ICU management in these patients should be assessed before admission and strategies aiming to improve these patients' outcome are urgently needed.