Rabbit model of Candida albicans biofilm infection: liposomal amphotericin B antifungal lock therapy

Abstract

Catheter-related infections due to Candida albicans biofilms are a leading cause of fungal nosocomial bloodstream infection. In this paper, we describe the development of a model of catheter-associated infection with C. albicans biofilms and show that antifungal lock therapy with liposomal amphotericin B is an effective treatment strategy for these infections. Silicone catheters surgically placed in New Zealand White rabbits were infected with C. albicans, and the rabbits were randomized into three groups: (i) untreated controls, (ii) liposomal amphotericin B lock, and (iii) fluconazole lock. Upon completion of therapy, blood cultures were obtained and the catheters were removed for quantitative culture and scanning electron microscopic analyses. Quantitative cultures revealed that catheters treated with liposomal amphotericin B yielded 0 CFU, which was significant compared to the untreated controls (P < 0.001) and the fluconazole-treated group (P = 0.0079). Although fluconazole treatment tended to have lower CFU compared to untreated controls, there was no difference in mean colony counts between these two groups (1.128 +/- 0.764 and 1.841 +/- 1.141 log(10) CFU/catheter segment, respectively; P = 0.297). Scanning electron microscopy revealed abundant biofilm in the control and fluconazole groups, while the liposomal amphotericin B group was virtually cleared. These findings suggest a possible treatment strategy for the successful salvage of catheters infected with C. albicans biofilms and describe an animal model that may play an important role in the further study of C. albicans biofilm pathogenesis and evaluation of potential antibiofilm agents.

Figures

FIG. 1.

Surgical placement of the intravenous catheter. (A to C) Catheter insertion into the external jugular vein; (D to F) attachment of the heparin lock device to skin; (G) postoperative venogram of catheter placement.

FIG. 2.

Mature in vivo biofilm formation during model development. Scanning electron micrographs of C. albicans biofilms adherent to the intraluminal surface of catheters showing no difference in biofilm architecture at 7 days postinfection (magnification, ×6,500) (A) and 3 days postinfection (magnification, ×2,500) (B) are shown.

FIG. 3.

Effectiveness of antifungal lock therapy. Scanning electron micrographs of intraluminal catheter surfaces following 7 days of therapy with heparinized saline (magnification, ×5,000) (A), liposomal amphotericin B (magnification, ×121) (B), and fluconazole (magnification, ×3,500) (C) are shown.