Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model

PURPOSE: We evaluate the efficacy of liposomal amphotericin (Fungisome) compared to conventional amphotericin (AMB) for the treatment of fungal keratitis (FK) in an experimental rabbit model. METHODS: FK was induced in 48 New Zealand White rabbits using Aspergillus flavus and Candida albicans (24 ra...

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Autores principales: Ghosh, Anup Kumar, Rudramurthy, Shivaprakash Mandya, Gupta, Amit, Choudhary, Hansraj, Singh, Shreya, Thakur, Anchal, Jatana, Manu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557587/
https://www.ncbi.nlm.nih.gov/pubmed/31205812
http://dx.doi.org/10.1167/tvst.8.3.35
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author Ghosh, Anup Kumar
Rudramurthy, Shivaprakash Mandya
Gupta, Amit
Choudhary, Hansraj
Singh, Shreya
Thakur, Anchal
Jatana, Manu
author_facet Ghosh, Anup Kumar
Rudramurthy, Shivaprakash Mandya
Gupta, Amit
Choudhary, Hansraj
Singh, Shreya
Thakur, Anchal
Jatana, Manu
author_sort Ghosh, Anup Kumar
collection PubMed
description PURPOSE: We evaluate the efficacy of liposomal amphotericin (Fungisome) compared to conventional amphotericin (AMB) for the treatment of fungal keratitis (FK) in an experimental rabbit model. METHODS: FK was induced in 48 New Zealand White rabbits using Aspergillus flavus and Candida albicans (24 rabbits each). Rabbits were divided into four groups: 0.1% and 0.05% Fungisome-, and 0.1% AMB-treated groups, and one untreated control group. Clinical scores were recorded throughout the study while fungal burden was estimated by corneal button culture on day 19 (study endpoint). RESULTS: A statistically significant improvement in clinical score was seen on day 11 in the 0.1% and 0.05% Fungisome versus untreated groups (13.91 and 14.4 vs. 19.3; P < 0.001) in the A. flavus model, and on day 9 in the 0.1% Fungisome-treated versus untreated groups (12.96 vs. 14.2; P = 0.006) in the C. albicans model. At endpoint, the mean clinical scores of the untreated controls, and the 0.1% and 0.05% Fungisome-, and 0.1% AMB-treated groups were 20 ± 1.4, 5.33 ± 1.85, 9.66 ± 2.41, and 8.16 ± 1.95, respectively, in the A. flavus model and 15.85 ± 1.87, 3.08 ± 1.31, 4.21 ± 1.370, and 4.13 ± 1.38, respectively, in the C. albicans model. Conjunctival hyperemia score was higher in the 0.1% AMB- versus 0.1% Fungisome-treated groups (1.33 vs. 0.5, P = 0.452). Lowest fungal burden in both models was seen in the 0.1% Fungisome-treated groups. CONCLUSIONS: Clinical improvement was observed with Fungisome relative to untreated controls. However, no statistically significant differences in outcomes were observed between animals treated with Fungisome and AMB. Although the results are encouraging, future studies in humans are warranted. TRANSLATIONAL RELEVANCE: FK is a leading cause of corneal blindness and is on the rise especially in developing countries. Despite the availability of various antifungal agents, heterogeneous treatment outcomes are seen due to lack of a standardized treatment regimen for FK. Although the use of liposomal AMB has been substantiated by clinical evidence in systemic infections, to our knowledge there are no in vivo studies evaluating the role of topical liposomal versus conventional formulation in FK. Our study investigated the efficacy and toxicity profile of liposomal versus conventional formulation of AMB in an experimental rabbit FK model.
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spelling pubmed-65575872019-06-14 Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model Ghosh, Anup Kumar Rudramurthy, Shivaprakash Mandya Gupta, Amit Choudhary, Hansraj Singh, Shreya Thakur, Anchal Jatana, Manu Transl Vis Sci Technol Articles PURPOSE: We evaluate the efficacy of liposomal amphotericin (Fungisome) compared to conventional amphotericin (AMB) for the treatment of fungal keratitis (FK) in an experimental rabbit model. METHODS: FK was induced in 48 New Zealand White rabbits using Aspergillus flavus and Candida albicans (24 rabbits each). Rabbits were divided into four groups: 0.1% and 0.05% Fungisome-, and 0.1% AMB-treated groups, and one untreated control group. Clinical scores were recorded throughout the study while fungal burden was estimated by corneal button culture on day 19 (study endpoint). RESULTS: A statistically significant improvement in clinical score was seen on day 11 in the 0.1% and 0.05% Fungisome versus untreated groups (13.91 and 14.4 vs. 19.3; P < 0.001) in the A. flavus model, and on day 9 in the 0.1% Fungisome-treated versus untreated groups (12.96 vs. 14.2; P = 0.006) in the C. albicans model. At endpoint, the mean clinical scores of the untreated controls, and the 0.1% and 0.05% Fungisome-, and 0.1% AMB-treated groups were 20 ± 1.4, 5.33 ± 1.85, 9.66 ± 2.41, and 8.16 ± 1.95, respectively, in the A. flavus model and 15.85 ± 1.87, 3.08 ± 1.31, 4.21 ± 1.370, and 4.13 ± 1.38, respectively, in the C. albicans model. Conjunctival hyperemia score was higher in the 0.1% AMB- versus 0.1% Fungisome-treated groups (1.33 vs. 0.5, P = 0.452). Lowest fungal burden in both models was seen in the 0.1% Fungisome-treated groups. CONCLUSIONS: Clinical improvement was observed with Fungisome relative to untreated controls. However, no statistically significant differences in outcomes were observed between animals treated with Fungisome and AMB. Although the results are encouraging, future studies in humans are warranted. TRANSLATIONAL RELEVANCE: FK is a leading cause of corneal blindness and is on the rise especially in developing countries. Despite the availability of various antifungal agents, heterogeneous treatment outcomes are seen due to lack of a standardized treatment regimen for FK. Although the use of liposomal AMB has been substantiated by clinical evidence in systemic infections, to our knowledge there are no in vivo studies evaluating the role of topical liposomal versus conventional formulation in FK. Our study investigated the efficacy and toxicity profile of liposomal versus conventional formulation of AMB in an experimental rabbit FK model. The Association for Research in Vision and Ophthalmology 2019-06-06 /pmc/articles/PMC6557587/ /pubmed/31205812 http://dx.doi.org/10.1167/tvst.8.3.35 Text en Copyright 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License.
spellingShingle Articles
Ghosh, Anup Kumar
Rudramurthy, Shivaprakash Mandya
Gupta, Amit
Choudhary, Hansraj
Singh, Shreya
Thakur, Anchal
Jatana, Manu
Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
title Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
title_full Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
title_fullStr Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
title_full_unstemmed Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
title_short Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
title_sort evaluation of liposomal and conventional amphotericin b in experimental fungal keratitis rabbit model
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557587/
https://www.ncbi.nlm.nih.gov/pubmed/31205812
http://dx.doi.org/10.1167/tvst.8.3.35
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