Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection—Scotland, 2012–2013

Abstract

Bloodstream infections caused by Candida species remain a significant cause of morbidity and mortality in hospitalized patients. Biofilm formation by Candida species is an important virulence factor for disease pathogenesis. A prospective analysis of patients with Candida bloodstream infection (n = 217) in Scotland (2012–2013) was performed to assess the risk factors associated with patient mortality, in particular the impact of biofilm formation. Candida bloodstream isolates (n = 280) and clinical records for 157 patients were collected through 11 different health boards across Scotland. Biofilm formation by clinical isolates was assessed in vitro with standard biomass assays. The role of biofilm phenotype on treatment efficacy was also evaluated in vitro by treating preformed biofilms with fixed concentrations of different classes of antifungal. Available mortality data for 134 patients showed that the 30-day candidaemia case mortality rate was 41%, with predisposing factors including patient age and catheter removal. Multivariate Cox regression survival analysis for 42 patients showed a significantly higher mortality rate for Candida albicans infection than for Candida glabrata infection. Biofilm-forming ability was significantly associated with C. albicans mortality (34 patients). Finally, in vitro antifungal sensitivity testing showed that low biofilm formers and high biofilm formers were differentially affected by azoles and echinocandins, but not by polyenes. This study provides further evidence that the biofilm phenotype represents a significant clinical entity, and that isolates with this phenotype differentially respond to antifungal therapy in vitro. Collectively, these findings show that greater clinical understanding is required with respect to Candida biofilm infections, and the implications of isolate heterogeneity.

Cambios clínicos y epidemiológicos de candidemias en pacientes adultos desde 2000 a 2013

“…Tampoco es posible extrapolar estos resultados a otros centros chilenos de complejidad similar pero, posiblemente hay ciertos aspectos comunes a otros centros, los que también pueden haber experimentado cambios epidemiológicos durante los últimos años. Otra limitación es la falta de una mejor definición para candidemia asociada a CVC, el impacto de su retiro en el desenlace, la falta de registro de inicio de antifúngicos y la no inclusión de la producción de biopelícula en los análisis de resultados por especie, ya que ha sido señalada cada vez con mayor frecuencia el último tiempo como un factor que impacta en el pronóstico 25 .…”

Screening the Pathogen Box for Identification of Candida albicans Biofilm Inhibitors

“…Fluconazole is one of the three main antifungal drugs used in the treatment of Candida infections, and for many years before the introduction of the echinocandins, it remained a first-line antifungal therapy for the treatment of candidiasis (13). However, it is well established that fluconazole is not active against preformed biofilms and can lead to treatment failure in biofilm-associated infections (5,23). Considering the fact that compound MMV688768 per se showed potent activity against preformed biofilms, we decided to evaluate if the combination of this compound with fluconazole could improve killing of C. albicans biofilms with reduced doses.…”

Candida albicans biofilm heterogeneity does not influence denture stomatitis but strongly influences denture cleansing capacity

“…Absorbance was read spectrophotometrically at 570 nm and isolates were grouped based on their level of biomass distribution. Isolates that fell below the 1 st quartile (Q 1 , OD 570 = 0.382) were classed as low biofilm formers (LBF) and strains with a biomass greater than the 3 rd quartile (Q 3 , OD 570 = 1.192) were deemed as high biofilm formers (HBF), as described previously (10,11).…”

“…However, the details of such surface interactions are not yet fully understood (8,9). Moreover, this problem is further compounded by the fact that C. albicans biofilms are clinically heterogeneous, and this phenotype has been shown to negatively impact patient outcomes (10)(11)(12). Whether this clinical heterogeneity plays a role in the intra-oral denture environment remains to be determined, as the influence of denture surfaces and methods of decolonisation needs to be considered.…”