Invasive pulmonary aspergillosis in critically ill patients with hematological malignancies

Intensive Care Med. 2019 Dec;45(12):1732-1741. doi: 10.1007/s00134-019-05789-6. Epub 2019 Oct 10.

Abstract

Purpose: Invasive pulmonary aspergillosis (IPA) is a dreadful event in patients with hematological malignancies (HM). Recent advances have standardized diagnostic, prophylactic and curative therapeutic strategies. We sought to assess whether these advances actually translate into improved survival in critically ill patients with acute respiratory failure and IPA.

Methods: This was a retrospective, multicenter study. Adult patients with HM, IPA, admitted to the ICU for acute respiratory failure over a 20-year period (January 1998-December 2017) were included. A cox regression model was used to identify variables independently associated with day-90 survival.

Results: Overall, 219 patients were included [138 (63%) men, median age 55 (IQR 44-64)]. Acute myeloid leukemia (30.1%) and non-Hodgkin lymphoma (22.8%) were the most frequent malignancies, and 53 (24.2%) were allogeneic stem cell recipients. Day-1 SOFA score was 9 [7-12]. Most patients presented with probable IPA, whereas 15 (7%) underwent lung biopsies or pleurocentesis and met criteria for proven IPA. Overall ICU and day-90 mortality were, respectively, 58.4% and 75.2% (80.4% if invasive mechanical ventilation) without any significant improvement over time. By multivariable analysis adjusted on day-1 SOFA score and ventilation strategies, voriconazole use (HR 0.49, CI 95 0.34-0.73, p < 0.001) and an ICU admission after 2010 (HR 0.67, 0.45-0.99, p = 0.042) were associated with increased survival, whereas a diffuse radiologic pattern (HR 2.07, CI 95 1.33-3.24, p = 0.001) and delayed admission to the ICU (HR 1.51, CI 95 1.05-2.16, p = 0.026) were independently associated with increased mortality.

Conclusions: IPA is associated with high mortality rates in critically ill patients with acute respiratory failure. Routine voriconazole and prompt ICU admission are warranted.

Keywords: Critically ill; Fungal infections; Hematological malignancies; Invasive pulmonary aspergillosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antifungal Agents / therapeutic use*
  • Female
  • Hematologic Neoplasms / complications*
  • Hematologic Neoplasms / mortality*
  • Humans
  • Invasive Pulmonary Aspergillosis / diagnosis
  • Invasive Pulmonary Aspergillosis / drug therapy*
  • Invasive Pulmonary Aspergillosis / etiology*
  • Invasive Pulmonary Aspergillosis / mortality*
  • Male
  • Middle Aged
  • Mortality
  • Retrospective Studies
  • Survival Rate
  • Voriconazole / therapeutic use*

Substances

  • Antifungal Agents
  • Voriconazole