Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Paul-Ehrlich Society for Chemotherapy, Divisions of Mycology and Pneumonia Research.

OBJECTIVE: To determine the epidemiological and clinical significance of invasive fungal infections in non-neutropenic patients in intensive care who stay longer than 10 days on the intensive care unit (ICU). DESIGN: Prospective epidemiological multicenter study over a period of 11 months, based on strict clinical, bacteriological, serological and histological criteria. SETTING: Six surgical and two medical ICUs units in five university and two municipal hospitals. PATIENTS: 435 non-neutropenic patients from medical and surgical ICUs with an ICU stay of more than 10 days. MEASUREMENTS AND MAIN RESULTS: A new occurrence of invasive mycosis (3 sepsis/4 peritonitis/1 disseminated candidiasis), corresponding to the protocol conditions with onset after day 10 in the ICU, was detectable in 2.0% (95% confidence interval 0.85 to 3.8%) of the 409 patients who could be assessed. Candida species were identified as an infection-relevant pathogen in all cases. The most important risk factor for the development of an invasive mycosis was the onset of peritonitis by the day 11 in the ICU (odds ratio 11.3; p = 0.003). A fungal colonization was detected in 64% of patients (Candida species 56%, Aspergillus 4%, and other fungi). Six of 8 patients with an invasive mycosis died on the ICU; ICU mortality in patients with fungal colonization was 31% and in noncolonized patients 26%. Serological tests were not helpful clinically. The sensitivity was 88% for the Candida HAT (haemagglutination test) (threshold titer > 1:160), 100% for the Candida IFT (immunofluorescence test) (threshold titer > 1:80), and 50% for the Candida Antigen Test (Candtec Ramco, threshold titer > or = 1:8), and the specificity was 26, 6, and 73%, respectively. The specificity for the Aspergillus HAT (threshold titer > 1:10) was 29%. CONCLUSIONS: Invasive mycoses are rare in non-neutropenic ICU patients, even after a longer stay in the intensive care unit; fungal colonization, on the other hand, is frequently detectable. The mortality of invasive mycosis--even with systemic antimycotic therapy--was high; the mortality in patients with fungal colonization was not significantly increased compared to that in noncolonized patients. The serological test procedures, Candida HAT, Candida IFT, and the Candida Ramco Antigen Test, had a low specificity and were not helpful in diagnosing relevant invasive mycosis.