EJRC Article Review
Invasive Candida infections are leading causes of mortality among critically ill patients. The diagnosis of such diseases is challenging and a delayed start of the appropriate antifungal therapy was associated with a poor prognosis. Accordingly, early empirical antifungal treatment is warranted on the basis of suspected diagnosis.
Observational studies have suggested that serological fungal biomarkers could be used to rule out the diagnosis of invasive Candida infections and consider an early discontinuation of empirical antifungal treatment without increasing the risk of mortality.
Rouzé et al. conducted a randomised, controlled, single-centre, open-label trial  with the aim to investigate whether the protocolled use of fungal biomarker results would increase the percentage of early discontinuation of empirical antifungal treatment as compared with standard therapy, among adult, immunocompetent, non-neutropenic critically ill patients with de novo suspected invasive Candida infections. Patients were randomly assigned to the intervention group, in which empirical antifungal treatment duration was determined by an algorithm based on (1,3)-β-d-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4 from randomisation; or to the control group, in which the empirical antifungal treatment of patients without subsequent proven invasive Candida infection and who improved under antifungal treatment lasted 14 days, according with the Infectious Diseases Society of America (IDSA) guidelines. In both groups, patients with confirmed invasive Candida infections received at least 14 days of antifungals.
No significant differences in terms of demographic and clinical characteristics were found between the intervention and control group. Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, as compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.0001, OR (95% CI) 62.6 (8.1– 486)]. The duration of empirical antifungal treatment was significantly shorter in the biomarker strategy compared with the routine strategy group. However, no significant differences were found in terms of clinical outcome and costs related therapies.
The result of the trial  supported the feasibility of a biomarker strategy to increase the percentage of patients undergoing early discontinuation of empirical antifungal therapy, in absence of negative impact on patients’ outcome, as compared with a routine strategy. By reducing the duration of antifungal treatment, the protocolled therapeutic strategy driven by biomarker results may reduce the deleterious effects of inappropriate overuse of antifungal therapy, including toxicity, antifungal resistance, drug interaction, and unnecessary costs.
The algorithm used in the trial was designed to rule out the diagnosis of invasive Candida infections, although it was not previously validated and the results may not be generalised due to the single-centre design of the study. Furthermore, the number of patients enrolled might be relatively small for a powerful evaluation of secondary outcomes, including safety, cost-effectiveness and long-term effects of an antifungal treatment duration driven by serological fungal biomarker results. Multicentre randomised controlled trials are warranted to confirm the result of this first important step forward in a such important topic.
Article review prepared and submitted by Salvatore Lucio Cutuli (EJRC member) and Gennaro de Pascale (NEXT committee member), Department of Intensive Care and Anaesthesiology, Catholic University of the Sacred Heart, ‘A. Gemelli’ Teaching Hospital, Rome, Italy.
1. Rouzé A, Loridant S, Poissy J et al (2017) Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomised controlled trial. Intensive Care Med Sept; online first. doi: 10.1007/s00134-017-4932-8.