Usefulness of quantitative analysis of beta-D-glucan in empirical therapy for systematic Candida infection in critically ill patients

Background

The clinical importance of systemic Candida infection in critically ill patients is a well-documented fact. However, it is not always true that early recognition of Candida infections followed by early pre-emptive antifungal therapy has been routinely done. Lack of an institutional written protocol for systemic Candida infections may lead to delayed diagnosis and treatment of such infections. It is expected that each institution has to establish its own clinical path to ensure a standardized team approach to systemic Candida infections to improve patient outcome.

Purposes

One is to review indications of antifungal therapy and evaluate the relationship between risk factors and values of beta-D-glucan. Another is to test usefulness of risk factors to predict the increased value of beta-D-glucan prospectively.

Patients and methods

Clinical records of 43 patients who received antifungal therapy for clinical diagnosis of systemic Candida infections were reviewed. Risk factors (APACHE score, Injury Severity Score [ISS], length of ICU stay, duration of mechanical ventilation, total blood transfusion within 48 hours, total parenteral nutrition, and signs of systematic inflammation), bacteriological studies, and quantitative data of beta-D-glucan (Fungitec G test MK, Seikagaku-kogyo, Japan) were analyzed. In a prospective study, 38 patients were followed to test the hypothesis that the risk factors (APACHE score >15 and ISS >16, ICU stay > 7 days, and mechanical ventilation > 2 days) can predict increased levels of beta-D-glucan (> 20 pg/ml), which validate pre-emptive antifungal therapy.

Results

In a retrospective study, positive culture for Candida remained low (37.2%); however, beta-D-glucan was increased significantly (> 20 pg/ml) in 79.5% of patients. In patient with APACHE score >15 and ISS >16, beta-D-glucan was increased in 78.4%. Beta-D-glucan was also increased in 79.0% of patients who stayed in the ICU longer than 7 days. In prospective study, 26.3% (10/38) of patients eventually received antifungal agents. Of these, eight patients (80.0%) fulfilled APACHE score >15, ISS >16, and ICU stay > 7 days.

Discussion

A certain combination of risk factors of systemic Candida infections was useful to identify the patient group who need pre-emptive antifungal therapy. Beta-D-glucan, which is a useful serologic test for fungal infections, was useful to initiate antifungal therapy in critically ill patients who fulfilled risk factors.

Conclusions

APACHE score >15, ISS >16 and ICU stay > 7 days were useful to discriminate patients who are prone to develop systemic Candida infections. Beta-D-glucan (> 20 pg/ml) is a useful clinical tool to initiate pre-emptive antifungal therapy in such circumstances.