8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide and fluconazole combination as a preventive strategy for Candida biofilm in haemodialysis devices

Abstract

Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters. Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity. Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs. Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time–kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation. Results. Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole. Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.