Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence

https://doi.org/10.1016/j.jhin.2004.01.006Get rights and content

Abstract

Invasive aspergillosis is a rare disease in intensive care unit (ICU) patients and carries a poor prognosis. The aim of the present study was to determine the attributable mortality due to invasive aspergillosis in critically ill patients. In a retrospective, matched cohort study (July 1997–December 1999), 37 ICU patients with invasive aspergillosis were identified together with 74 control patients. Matching of control (1:2) patients was based on the acute physiology and chronic health evaluation (APACHE) II classification: an equal APACHE II score (±1 point) and diagnostic category. This matching procedure results in an equal expected in-hospital mortality for cases and controls. Additionally, control patients were required to have an ICU stay equivalent to or longer than the case before the first culture positive for Aspergillus spp. Patients with invasive aspergillosis were more likely to experience acute renal failure (43.2% versus 20.5%; P=0.020). They also had a longer ICU stay (median: 13 days versus seven days; P<0.001) as well as a more extended period of mechanical ventilator dependency (median: 13 days versus four days; P<0.001). Hospital mortalities for cases and controls were 75.7% versus 56.8%, respectively (P=0.051). The attributable mortality was 18.9% (95% CI: 1.1–36.7). A multivariate survival analysis showed invasive aspergillosis [hazard ratio (HR): 1.9, 95% CI: 1.2–3.0; P=0.004] and acute respiratory failure (HR: 6.5, 95%: 1.4–29.3; P<0.016) to be independently associated with in-hospital mortality. In conclusion, it was found that invasive aspergillosis in ICU patients carries a significant attributable mortality of 18.9%. In a multivariate analysis, adjusting for other co-morbidity factors, invasive aspergillosis was recognized as an independent predictor of mortality.

Introduction

The importance of fungi as pathogens in intensive care units (ICUs) is increasing as a result of advances in life-support systems, wider use of broad-spectrum antibiotics and invasive devices, and an increasing proportion of susceptible patients.1 Nosocomial invasive aspergillosis can occur in any severely immunocompromised or chronically debilitated host. It is by far the greatest infectious threat to survival, in the setting of profound granulocytopenia during and after induction chemotherapy, bone marrow transplantation and certain solid-organ transplant patients. Conversely, cases of community-acquired pulmonary infection due to Aspergillus spp. have been described in presumably immunocompetent individuals. Intercurrent invasive pulmonary aspergillosis has been associated with chronic obstructive pulmonary disease (COPD) and influenza pneumonitis in patients with other pre-existing structural lung disease, as well as in patients with acquired immunodeficiency syndrome (AIDS). The development of respiratory failure in the disease heralds a particularly poor prognosis. Despite adequate anti-fungal therapy, mortality varies from 50 to 100%. There are substantial variations depending on patient characteristics.2., 3. Few studies describe the epidemiology and outcome of invasive aspergillosis in ICU patients, without any data on attributable mortality. In view of the severe underlying disease of such patients, it is often very difficult to distinguish mortality attributable to fungal infection, from mortality due to disease. In this context, matched cohort studies are more appropriate in determining attributable mortalities.4 The primary objective of the present study was to determine outcome and attributable mortality of invasive aspergillosis infections in patients admitted to a general ICU by means of a matched cohort study. The secondary objective of this study was to investigate the excess length of stay in the ICU, as well as the excess length of mechanical ventilator dependency in ICU patients with invasive aspergillosis as these are the utmost important indicators for cost estimation in ICU setting.

Section snippets

Setting

The present study was conducted in the Ghent University Hospital, a 1060-bed, tertiary care centre with a 54-bed ICU, including a surgical and medical ICU, an ICU for cardiac surgery and a unit for severely burned patients. Approximately 3300 patients are admitted to the ICU each year. The surgical ICU provides all types of surgery with the need for intensive care management, including multiple trauma and solid-organ transplantations (kidney, liver and pancreas). The medical ICU serves all

Results

During the study period there were 8988 admissions in the ICUs. Of these patients, 71 were identified with positive cultures for Aspergillus spp. According to the predefined criteria 37 were classified as cases with either definite or probable invasive aspergillosis, representing an incidence of four out of 1000 ICU admissions. In 10 patients the diagnosis was definite (pulmonary involvement, two patients; pulmonary and other organ involvement, eight patients). The diagnosis of probable

Discussion

Although formerly considered to be a rare disease, invasive aspergillosis is now recognized as an emerging opportunistic infection in the critically ill. In the present study, the incidence of invasive aspergillosis in general ICU patients was four in 1000 patients. Groll et al. reported the trends of invasive mycoses from autopsy findings in a German university hospital and found a 14-fold rise in prevalence over a 12-year period.21 A large nationwide Japanese study of unselected autopsies

Acknowledgments

The authors thank P. De Waegemaeker (RN, MA) from the Hospital Hygiene Team, Ghent University Hospital, for providing microbiological data.

References (32)

  • W.A Knaus et al.

    APACHE II: a severity of disease classification system

    Crit Care Med

    (1985)
  • D Pittet et al.

    Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality

    J Am Med Assoc

    (1994)
  • W Temmerman et al.

    Invasive aspergillosis in the ICU: incidence and characteristics

    Intensive Care Med

    (2000)
  • S Ascioglu et al.

    Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus

    Clin Infect Dis

    (2002)
  • J Rello et al.

    Evaluation of outcome of intravenous catheter-related infections in critically ill patients

    Am J Respir Crit Care Med

    (2000)
  • S.I Blot et al.

    Clinical impact of nosocomial Klebsiella bacteremia in critically ill patients

    Eur J Clin Microbiol Infect Dis

    (2002)
  • Cited by (108)

    View all citing articles on Scopus

    Presented in part at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 2001.

    1

    Tel.: +32-9-240-62-16; fax: +32-9-240-49-95.

    View full text