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Liposomal Amphotericin B Shows Poor Antifungal Activity Against Candida Tropicalis Biofilms L.J

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Liposomal Amphotericin B Shows Poor Antifungal Activity Against Candida Tropicalis Biofilms L.J Liposomal amphotericin B shows poor antifungal activity against Candida tropicalis biofilms L.J. Marcos- Zambrano1,2 ,P. Escribano1,2,3, E. Bouza1,2,3,4, J. Guinea1,2,3,4 EP0063 1 Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 2 Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. 3 CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain. 4 Medicine Department, Faculty of Medicine, Universidad Complutense de Madrid INTRODUCTION RESULTS Candidemia caused by Candida tropicalis present high mortality rates and is often associated with biofilm formation Most of isolates were classified as high- The three drugs showed activity against the isolates in planktonic form, with on implanted medical devices. biofilm forming according to crystal violet micafungin showing the highest activity (P<0.001). Echinocandins and amphotericin B have shown potent in assay (83%) and showed moderate L-AmB showed the lowest antibiofilm activity (P<0.05). MYC and AmB showed similar vitro antibiofilm activity against C.albicans biofilm, but little is metabolic activity (56%) according to activity when the SMIC50 endpoint was used whereas MYC was the most active agent known about the activity against C. tropicalis biofilms. XTT reduction assay. when the SMIC80 endpoint was used (P<0.001). OBJECTIVE Table 1. Antifungal activity of MYC, AmB and L-AmB against C. tropicalis isolates in plancktonic and sessile forms; SMIC and SMIC are provided for the latter forms. We studied the biofilm production and antifungal 50 80 susceptibility of 54 C. tropicalis isolates causing candidemia (2007 to 2015) to micafungin, amphotericin B, and liposomal Planktonic MIC (mg/L) SMIC50 (mg/L) SMIC80 (mg/L) amphotericin B (Ambisome ®) MYC AmB L-AmB MYC AmB L-AmB MYC AmB L-AmB METHODS Geometric mean 0.026 0.53 0.22 0.72 0.87 1.80 9.82 14.07 30.39 54 C. tropicalis isolates from blood cultures P < 0.05 P < 0.05 P < 0.05 Molecular identification by amplification of the C. tropicalis biofilms were formed by In contrast, the exposure to MYC promoted significant alterations in the biofilm structure consisting ITS1-5.8S-ITS2 region a dense and thick web of hyphae. on a reduction in the number of hyphae, and the presence of swollen blastospores. L-AmB induced subtle changes on The differences are consistent with the antifungal susceptibility testing as both the SMIC50 and the biofilm structure. SMIC80 were much lower for MYC than for both forms of amphotericin B. Classification according to biofilm production (a) (b) (c) Biomass (Crystal violet) Metabolic activity (XTT) Low, moderate and high Low, moderate, and high biofilm forming metabolic activity Antifungal susceptibility to Micafungin (MYC), Amphotericin B (AmB), and liposomal amphotericin B (L-AmB) EUCAST XTT (Planktonic form) (Biofilm form) 20µm 20µm 20µm Figure 1. SEM images showing the impact of the exposure of the biofilm formed by the C. tropicalis strain. (a) Untreated control; (b) Isolate exposed to MYC [SMIC80=0.031 mg/L]; (c) Isolate exposed to L-AmB [SMIC80=16 mg/L]. 2000 X magnification. Scanning Electron Microscopy (SEM) CONCLUSIONS Treated and non-treated biofilms Micafungin was the drug showing the highest antibiofilm activity against C. tropicalis. L-AmB showed poor activity against C. tropicalis biofilms. This study was supported by FIS PI14/00740 .
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