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Published on: December 18, 2012
Evaluation of Liposomal and Conventional Amphotericin B in Experimental Fungal Keratitis Rabbit Model
Anup Kumar Ghosh1, Shivaprakash Mandya Rudramurthy1, Amit Gupta2
1Department of Medical Microbiology, PGIMER, Chandigarh, India.
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.
Insights
Liposomal amphotericin (Fungisome) showed clinical improvement for fungal keratitis (FK) in rabbits compared to controls. However, Fungisome and conventional amphotericin (AMB) demonstrated similar efficacy in this FK rabbit model.
Area of Science:
- Ophthalmology
- Mycology
- Pharmacology
Background:
- Fungal keratitis (FK) is a significant cause of corneal blindness, particularly in developing nations.
- Treatment outcomes for FK are often inconsistent due to a lack of standardized regimens.
- Liposomal amphotericin B (AMB) has established efficacy in systemic fungal infections, but its topical application for FK requires further investigation.
Purpose of the Study:
- To compare the efficacy of topical liposomal amphotericin (Fungisome) against conventional amphotericin B (AMB) for treating experimental fungal keratitis (FK) in rabbits.
- To evaluate the efficacy of two different concentrations of Fungisome (0.1% and 0.05%) and one concentration of AMB (0.1%) in a rabbit FK model.
Main Methods:
- Experimental FK was induced in 48 rabbits using *Aspergillus flavus* or *Candida albicans*.
- Rabbits were randomized into four groups: 0.1% Fungisome, 0.05% Fungisome, 0.1% AMB, and an untreated control group.
- Clinical scores were assessed throughout the study, and fungal burden was quantified by corneal button culture at the study endpoint (day 19).
Main Results:
- Both 0.1% and 0.05% Fungisome significantly improved clinical scores compared to controls in the *A. flavus* model by day 11.
- In the *C. albicans* model, 0.1% Fungisome showed significant improvement by day 9 compared to controls.
- The lowest fungal burden in both models was observed in the 0.1% Fungisome-treated group, although no statistically significant differences in clinical outcomes were found between Fungisome and AMB treatments.
Conclusions:
- Topical Fungisome demonstrated clinical efficacy in treating experimental fungal keratitis in rabbits.
- No statistically significant differences in treatment outcomes were observed between liposomal amphotericin (Fungisome) and conventional amphotericin B (AMB).
- Further clinical studies in humans are warranted to confirm these findings and establish optimal treatment protocols for FK.
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