Mind the gaps: challenges in the clinical management of invasive candidiasis in critically ill patients.

Abstract

Strict adherence to clinical practice guidelines is recognized to improve outcomes but the inconvenient truth is that only a small subset of what is done in medicine has been tested in appropriate, well designed studies. In this article, we aim to review controversial aspects of the clinical management of invasive candidiasis recommended by guidelines. Despite still being recommended by guidelines, we fail to identify a single randomized clinical trial documenting that the use of antifungal drugs in high-risk critically ill patients without microbiologic documentation of Candida infection decreases mortality. Regarding deep-seated Candida infections, most cohort studies of patients with candidemia found less than 5% of patients developed endophthalmitis and endocarditis. In this scenario, it is reasonable to reconsider routine universal screening of both complications in candidemic patients. Finally, a large number of studies have shown that critically ill patients usually have lower echinocandin exposure when compared with other populations. We need more data on the clinical relevance of this finding. We need robust studies to validate new strategies for the clinical management of candidemia in ICU, including: the use of fungal biomarkers in the early initiation or interruption of antifungal therapy in high-risk patients to replace the conventional empirical antifungal therapy driven by predictive rules; validation of targeted screening of eye infection and endocarditis with the aid of fungal biomarkers only in high-risk patients; we should clarify if higher doses of candins are necessary to treat invasive candidiasis in critically ill patients, especially in the case of intra-abdominal infections where drug penetration is suboptimal.