Candidemia in non-neutropenic critically ill patients: analysis of prognostic factors and assessment of systemic antifungal therapy

Abstract

Objective: To determine the incidence and prognosis of candidemia in non-neutropenic critically ill patients, to define mortality-related factors, and to evaluate the results of systemic antifungal therapy.

Design: A prospective multicenter survey in which medical and/or surgical intensive care units (ICUs) in 28 hospitals in Spain participated.

Patients: All critically ill patients with positive blood cultures for Candida species admitted to the participating ICUs over a 15-month period were included.

Interventions: Candidemia was defined as the presence of at least one positive blood culture containing Candida species. The follow-up period was defined as the time elapsed from the first positive blood culture for Candida species to discharge or death during hospitalization. Antifungal therapy was considered to be “early” when it was administered within 48 h of the date when the first positive blood culture was obtained and “late” when it was administered more than 48 h after the first positive blood culture.

Measurements and main results: Candidemia was diagnosed in 46 patients (mean age 59 years), with an incidence of 1 critically ill patient per 500 ICU admissions. The species most frequently isolated were Candida albicans (60%) and C. parapsilosis (17%). Fluconazole alone was given to 27 patients, amphotericin B alone to 10, and sequential therapy to 6. Three patients did not receive antifungal therapy. The overall mortality was 56% and the attributable mortality 21.7%. In the univariate analysis, mortality was significantly associated with a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score at the onset of candidemia (p=0.04) and with the time elapsed between the episode of candidemia and the start of antifungal therapy 48 h or more later (p<0.02). Patients with an APACHE II score lower than 21 at the onset of candidemia had a higher probability of survival than patients who were more seriously ill (p=0.04). Patients with “early” antifungal therapy (≤48 h between the onset of candidemia and the start of antifungal therapy) had a higher probability of survival compared with patients with late therapy (p=0.06). No significant differences were noted between the two groups on different antifungal therapy.

Conclusions: The incidence of candidemia in ICU patients was very low. An APACHE II score >20 at the time of candidemia was associated with a higher mortality. Further studies with a large number of patients are needed to assess the effect of early antifungal therapy on the decrease in mortality associated with candidemia and to determine the appropriate dosage of fluconazole and duration of treatment.