Comparison of micafungin and fluconazole for experimental Candida keratitis in rabbits.
OBJECTIVE
To evaluate the efficacy of subconjunctival injection of micafungin in the treatment of experimental Candida albicans keratitis in rabbits compared with fluconazole.


METHODS
In 1 eye of 24 New Zealand white rabbits, C. albicans (5 x 10 yeast cells) was inoculated in the corneal stroma. The animals were randomly assigned to 3 groups and received subconjunctival injection of 0.5 mL of 0.1% micafungin, 0.2% fluconazole, or physiologic saline once a day for 3 weeks. The eyes were examined slit-lamp biomicroscopically and histopathologically. The clinical course of fungal keratitis was compared among the 3 groups. In another 36 rabbits, a microbiological examination was performed using a quantitative isolate recovery technique, and the numbers of colony-forming units were compared among groups.


RESULTS
The clinical scores were significantly lower in the micafungin group than in the other 2 groups throughout the study period (P < 0.0001 approximately P = 0.0027, Bonferroni multiple comparison). The fluconazole group showed significantly lower clinical scores than the saline group on day 18 (P = 0.0343). At the end of the study period, there were significant differences between the saline and micafungin groups (P < 0.0001), the saline and fluconazole groups (P = 0.0072), and the fluconazole and micafungin groups (P = 0.0013). Histopathologically, similar results were obtained. Moreover, the results of the microbiological examination nearly matched the clinical and histopathologic findings.


CONCLUSIONS
Subconjunctival administration of micafungin was effective in the treatment of experimental Candida keratitis. Local application of micafungin to the eye would be a feasible treatment option for clinical fungal keratitis.
Hiraoka
Takahiro
T
Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. thiraoka@md.tsukuba.ac.jp
Kaji
Yuichi
Y
Wakabayashi
Taketoshi
T
Nanbu
Patricia N
PN
Okamoto
Fumiki
F
Oshika
Tetsuro
T
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D002177:Candidiasis / Q000188:drug therapy* / Q000503:physiopathology; D003228:Conjunctiva / Q000187:drug effects; D004195:Disease Models, Animal; D054714:Echinocandins; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000503:physiopathology; D015725:Fluconazole / Q000008:administration & dosage*; D007267:Injections; D007634:Keratitis / Q000188:drug therapy* / Q000503:physiopathology; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage*; D008297:Male; D000077551:Micafungin; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D011817:Rabbits
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D015725:Fluconazole; D000077551:Micafungin