Comparison of Two Antifungal Agents, Natamycin and Micafungin, for Fungal Keratitis

Abstract

Abstract: : Purpose: To evaluate the efficacy of the new antifungal Micafungin (FK–463) vs traditional therapy with natamycin in the treatment fungal keratitis in rabbit eyes. Methods:Three groups of six New Zealand white rabbits (n=18) were studied: 1 control and 2 treatment groups, in an IACUC–approved protocol. Experimental keratitis was induced by surgical inoculation with 0.1 ml of an Aspergillus fumigatus suspension (1x10⁷ CFU/ml.) in the midstromal cornea OD of all rabbits. The rabbits were then randomized to treatment with topical micafungin (Fujisawa) 150µg QID OU, natamycin (Alcon) 5% suspension QID OU, or normal saline QID OU. Treatment was started when the central corneal infiltrate was >2mm in diameter. The fellow eyes (OS) served as uninfected controls for topical therapy. The epithelial defect, the infiltrate and the hypopyon were evaluated and measured every day along with any reactive changes in the OS. Rabbits were sacrificed at day 8. Results:16 eyes developed a corneal infiltrate that was at least 2mm in diameter within 48 hours of inoculation; 2 eyes took 72 hours to reach qualifying size. Mean corneal lesion sizes throughout days 2–8 among eyes treated with either natamycin and micafungin were smaller than those in the eyes treated with saline, both in terms of the size of the epithelial defect [saline control 30.4 SD 6.1 mm²; natamycin 19.3 SD 3.3 mm² (P=0.003); micafungin 21.0 SD 7.2 mm² (P=0.03)], and the area of infiltrate [saline control 31.8 SD 3.9 mm²; natamycin 22.6 SD 5.8 mm² (P=0.009); micafungin 25.7 SD 6.7 mm² (P=0.08)]. There was no significant difference between drug treatment groups for either parameter (P=0.4 and 0.6, respectively). Hypopyon size was also significantly reduced with both antifungals [saline control 2.6 SD 1.0 mm; natamycin 1.6 SD 0.2 mm (P<0.001); micafungin 1.0 SD 0.6 mm (P=0.01)]. The only statistically significant difference between the two drug treatments was in hypopyon height, which was significantly lower with micafungin (mean difference=0.65mm; p=0.03). No evidence of any adverse effects were observed in any of the noninfected, drug treated left eyes. Conclusions:Micafungin and natamycin were well tolerated and were both significantly effective in limiting the size of aspergillus keratitis epithelial lesions. Mean infiltrate size was significantly lowered with natamycin, with no significant difference between drug treatments. Both drugs reduced leukocyte accumulation in the anterior chamber, though hypopya were of significantly greater size with natamycin than with micafungin therapy.

Keywords: fungal disease • antibiotics/antifungals/antiparasitics • keratitis