The entomopathogenic fungi belonging to the genus Beauveria are rare pathogens in humans, and only 11 cases of keratitis due to Beauveria species have been reported[4–13]. Because of the limited number of cases, the clinical features of B. bassiana keratitis have not been determined. The course of our non-necrotic keratitis case was slow-growing, there was no clinical improvement after treatment with voriconazole even though voriconazole was the preferable antibiotic according to the sensitivity tests. The cases of B. bassiana reported by Low et al., Kisla et al., and Tu et al., were also slow-growing with late penetration into the corneal stroma which is consistent with our case[6, 7, 12]. In addition, the resistance to antifungal therapy was also consistent with our case[6–8, 12].
Our antifungal susceptibility tests showed that the isolated strain was sensitive to micafungin and voriconazole and moderately sensitive to natamycin. There have been several reports on the drug sensitivity of B. bassiana. Tu et al. and Figueira et al. reported that both of their strains were sensitive to posaconazole and voriconazole but resistant to amphotericin. These sensitivities are similar to that of our strain of B. bassiana[5, 12]. The results of Sonoyama et al. showed that the drug sensitivity of their Beauveria species was similar to our strain[11]. In addition, voriconazole was ineffective in both cases. Otherwise, the clinical course of the two cases was very similar, viz., slow-growing, non-necrotic keratitis, and clinically resistant to voriconazole. However, the causative strain was sensitive to voriconazole. Sonoyama et al. also had a successful treatment with topical voriconazole, although they also treated the eye with topical miconazole and oral itraconazole which their strain was sensitive to[11].
The results of the temperature sensitivity profile supported the microbiological results reported by Figueira et al.[5]. The temperature in the anterior chamber of the eye is generally 35°C or higher, and that of the corneal surface is 35°C or lower depending on the ambient temperature[17, 18]. Thus, we suggest that the B. bassiana strain in our case could not grow at temperatures of 35°C or higher and thus did not penetrate into the corneal stroma. This temperature sensitivity might be one reason why B. bassiana is a rare pathogen in humans, and why the infections in humans are limited to the body surface such as the cornea.
Another reason for the infection of the cornea may be the ability of B. bassiana to produce chitinase which lyses not only chitin but also keratin and collagen. This would then enable it to adhere and penetrate the cornea[5, 12]. B. bassiana has 3 different cell forms and can adhere to both hydrophobic and hydrophilic surfaces. This would enhance its adherence to the corneal surface along with the permissive avascular immune environment of the central cornea[5, 12]. In addition, the slow-growing property may be one of the reasons why the initial intensive antifungal therapy seemed to be clinically ineffective, because voriconazole works by preventing fungi from producing ergosterol which is a component of fungal cell membranes, and ergosterol is necessary for fungi to proliferate. Thus, the initial treatment with voriconazole only appeared to be ineffective in such slow-growing fungi. Although the clinical course was very slow, the infectious lesion improved after changing the treatment from natamycin eye ointment to topical micafungin and surgical debridement.
Micafungin is a echinocandins which blocks fungal cell wall beta-glucan synthesis, thus the different actions of voriconazole and micafungin may have a synergetic effect. It is also possible that the surgical debridement might have worked in our case because it removed antigenic and infectious elements and necrotic tissues. This supports the results of earlier studies that surgical debridement or keratectomy is required for mycotic keratitis that respond poorly to medical therapy[19, 20]. Further experiments on animals may be helpful in testing this hypothesis.