In vitro antifungal activity and in vivo antibiofilm activity of cerium nitrate against Candida species.

Abstract

Received 11 September 2014; returned 31 October 2014; revised 17 November 2014; accepted 23 November 2014Objectives: The objective of this study was to clarify the antifungal properties of cerium, a lanthanide member,against Candida species. A comprehensive study with planktonic and sessile cells was performed. The ability ofcerium nitrate (CN) to impair in vitro and in vivo biofilm formation was evaluated and its potential use in biofilmtreatment was also evaluated.Methods: Forty-eight clinical isolates of different Candida species and the type strain ATCC 90028 were testedaccording to the protocol M27-A3. The MICs and minimum lethal concentrations were determined. A time–killassay was performed and a cytometric kinetic study was performed using live/dead markers. Biofilm inhibitionand biofilm susceptibility in the presence of cerium was evaluated by quantification of the biofilm metabolicactivityandtotalbiomasswithXTTandcrystalvioletassays,respectively.CNin vivo efficacyasacoatingformed-ical indwelling devices was evaluated for the first time for Candida parapsilosis, using a mouse subcutaneousforeign body model using polyurethane catheter segments. Scanning electron microscopy was used to assessbiofilm architecture after CN treatment.Results: The MICs for planktonic cells correlated with severe cellular metabolic activity impairment and mem-brane damage after 3 h of incubation. Moreover, CN efficiently prevented biofilm formation both in vitro andin vivo in segments of polyurethane catheters. At higher concentrations, it was also able to disorganize andalmost eradicate preformed biofilms.Conclusions:Our results strongly suggest that CN application in the clinical setting might be effective inpreventing the formation of biofilm-associated infections, namely through catheter coating and ultimately asan antimicrobial lock therapy.Keywords: central venous catheters, healthcare-related infections, CVCs