Abstract
Candidaemia is a common life-threatening disease among hospitalised patients, but the effect of the Candida biofilm-forming ability on the clinical outcome remains controversial. The aim was to determine the impact of biofilms, specifically focusing on biofilm mass and metabolic activity, on the mortality in candidaemia. The clinical data of patients (n=127) treated at the University of Debrecen, Clinical Centre, between January 2013 and December 2018, were investigated retrospectively. Biofilm formation was assessed using the crystal violet and XTT assays, measuring the biofilm mass and metabolic activity, respectively. Isolates were classified as low, intermediate and high biofilm producers both regarding biofilm mass and metabolic activity. The susceptibility of one-day-old biofilms to fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin was evaluated and compared to planktonic susceptibility. Intermediate/high biofilm mass was associated with significantly higher mortality (61%). All Candida tropicalis, Candida parapsilosis and Candida glabrata isolates originating from fatal infections were intermediate/high biofilm producers, whereas this ratio was 85% for Candida albicans. Solid malignancy was associated with intermediate/high biofilm producers (p=0.043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, p=0.010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs. 28%, p=0.015). This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidemia.
Highlights
Candidaemia is the fourth and sixth most common bloodstream infection among hospitalised patients in the United States of America and Europe, respectively, accounting for 8%-15% of all nosocomial bloodstream infections.[1,2,3,4] Candidaemia episodes are associated with unacceptably high overall mortality ranging from 38% to 75%.5-7 A population-based surveillance from Italy revealed that biofilm production in Candida isolates is significantly associated with central venous or urinary catheter use and administration of total parenteral nutrition in the host patient.[8]
Biofilm formation is a key virulence factor for Candida species; it serves as a focus in bloodstream infections, protects the fungal cells against the immune response; the presence of biofilms is associated with reduced susceptibility to antimicrobial agents.[9]
Most studies addressing the association between fungal biofilms and patient parameters characterise biofilm production using either of the two approaches; these two measurements are not interchangeable, that is a biofilm with high biofilm mass may show low metabolic activity or vice versa
Summary
Candidaemia is the fourth and sixth most common bloodstream infection among hospitalised patients in the United States of America and Europe, respectively, accounting for 8%-15% of all nosocomial bloodstream infections.[1,2,3,4] Candidaemia episodes are associated with unacceptably high overall mortality ranging from 38% to 75%.5-7 A population-based surveillance from Italy revealed that biofilm production in Candida isolates is significantly associated with central venous or urinary catheter use and administration of total parenteral nutrition in the host patient.[8]. It is possible that some clinical parameters are differently associated with the biofilm-related variables
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