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In vivo evaluation of voriconazole eye drops efficacy in a rat Acanthamoeba polyphaga keratitis model
Author(s) -
Gueudry J.,
Le Goff L.,
Compag P.,
Lefevre S.,
Camille A.,
Duval F.,
Francois A.,
Razakandrainibe R.,
Favennec L.,
Muraine M.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.04435
Subject(s) - voriconazole , acanthamoeba keratitis , acanthamoeba , in vivo , cornea , keratitis , microbiology and biotechnology , medicine , pharmacology , fungal keratitis , biology , ophthalmology , antifungal
Purpose Acanthamoeba keratitis is a sight‐threatening infectious disease. Its effective and safe medical therapy remains highly debated. The aim of this study is to test in vitro and in vivo voriconazole as a potential antiamoebic treatment for Acanthamoeba keratitis. Methods In vitro sensitivity of Acanthamoeba polyphaga to voriconazole was assessed using a commercially available viability assay. In vivo , Sprague‐Dawley male rats were injected in the left cornea stromal layer with trophozoites. Forty rats were divided into 3 groups, topically treated with 1% voriconazole eyedrop (hourly administrations for 3 days followed by every two hours for 11 days and followed every four hours for 7 days), orally treated with voriconazole (60 mg/kg/day), and control. At day 28, cornea and blood samples were collected and corneal scrapings were performed for bacterial and parasitological cultures and real‐time PCR analyses. Paraffin‐embedded corneas were analyzed. The plasma and corneal concentration of voriconazole was determined by high‐performance liquid chromatography. Results In vitro , voriconazole inhibited Acanthamoeba polyphaga trophozoites proliferation with IC 90 value of 6 μ g/ml, however no cystical activity was found. Mean intracorneal concentration of voriconazole eyedrops after three days treatment was 5.6 +/‐ 4.4 ng / mg; after seven days treatment was 2.38 + /1.6 ng/mg; and after twenty one days treatment was 0.32 +/‐ 0.15 ng / mg. Clinical infection worsened in fewer rats between the 7th and the14th day post infection in the voriconazole eye drops group (1/10 rats) and the control group (9/10 rats) (p = 0.001). Conclusions Our findings support the potential use of voriconazole as anti‐amoebic agents.