New Markers for the Diagnosis of Invasive Fungal Disease

Abstract

The incidence in the intensive care unit of invasive fungal infections, including invasive aspergillosis (IA) and candidiasis (IC), increased during these last decades. Outcome remains tightly linked to the delay of treatment administration. Routine microbiological techniques give too late results to allow prompt antifungal therapy. They are even sometimes unable to diagnose the infection since almost 50% of the blood cultures are negative in IC. Therefore, other tools like biomarkers are needed to help building new therapeutic strategies. Biomarkers derive from structural, enzymatic, or metabolic components of fungi. Polysaccharide antigens from the cell wall or antibodies recognizing them can be routinely used. β-D-1,3-glucan is an ubiquitous biomarker, useful for IC, IA, and pneumocystis pneumonia diagnosis. It becomes early positive and represents a sensitive but not a specific biomarker. At the opposite, mannane is an antigen from Candida, specific but not sensitive for IC diagnosis and becoming positive later in the infection course than β-D-1,3-glucan. Galactomannane is specific and quite sensitive for Aspergillus. It becomes early positive for IA diagnosis, despite numerous causes of false positivity. Related antibodies have variable performance, but their kinetics appears interesting to follow-up. The use of these biomarkers for preemptive treatments or at the opposite to decrease the number of empiric prescriptions may help rationalizing antifungal management and increasing the rapidity of treatment administration. Further progresses are expected, relying on new molecular targets and assays based on new biotechnologies.