Efficacy of anidulafungin in the treatment of experimental Candida parapsilosis catheter infection using an antifungal-lock technique.

ABSTRACT

OBJECTIVES: The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed. METHODS: Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs. An intravenous catheter was implanted in New Zealand white rabbits. Infection was induced by locking the catheter for 48 h with the inoculum. The 48 h antifungal-lock treatment groups included control, 3.3 mg/mL anidulafungin and 5.5 mg/mL LAmB. RESULTS: Anidulafungin showed better in vitro activity than LAmB against C. parapsilosis growing in biofilm on silicone discs. MBIC90 of LAmB CP12, >1024 mg/L; CP54, >1024 mg/L. MBIC90 of anidulafungin CP12, 1 mg/L; CP54, 1 mg/L (P ≤ 0.05). Moreover, only anidulafungin (1 mg/L) showed >90% non-viable cells in the LIVE/DEAD biofilm viability assay on silicone discs. No differences were observed between the in vitro susceptibility of anidulafungin or LAmB when 96-well plates were used. Anidulafungin achieved significant reductions relative to LAmB in log10 cfu recovered from the catheter tips for both strains (P ≤ 0.05). Only anidulafungin achieved negative catheter tip cultures (CP12 63%, CP54 73%, P ≤ 0.05). CONCLUSIONS: Silicone discs may be a more reliable substrate for the study of in vitro biofilm susceptibility of C. parapsilosis. Anidulafungin-lock therapy showed the highest activity for experimental catheter-related infection with C. parapsilosis.