Background

Fungal keratitis is a common but severe eye infection in tropical and subtropical areas of the world. In regions with a temperate climate the frequency is rising in patients with contact lenses and following trauma. Early and adequate therapy is important to prevent disease progression and loss of vision. The management of Fusarium keratitis is complex, and the optimal treatment is not well defined. We investigated the in vitro activity of chlorhexidine and seven antifungal agents against a well characterized collection of Fusarium isolates, recovered from patients with Fusarium keratitis. Patients and methods The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for Fusarium isolates that were cultured from cornea scrapings, ocular biopsies, eye swabs and contact lens fluid containers from patients suspected of keratitis. The Fusarium isolates that were cultured from patients with confirmed keratitis were all identified using conventional and molecular techniques. Antifungal susceptibility testing was performed according to the EUCAST broth microdilution reference method. The antifungal agents tested included amphotericin B, voriconazole, posaconazole, miconazole, natamycin, fluorocystosine, and caspofungin. In addition, the activity of chlorhexidine was determined.   on June 20, 2019 by guest http://aac.asm.org/ Downloaded from  Results

The fungal culture collection contained 98 Fusarium isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between  2007 and 2017. F. oxysporum (n=24, 24.5%) was the most frequently isolated species followed by F. solani sensu stricto (n=18, 18.4%) and F. petroliphilum (n=11, 11.2%). In vitro amphotericin B was the most active antifungal drug followed by natamycin, voriconazole, posaconazole, and miconazole. Chlorhexidine showed activity against all. Fluorocytosine showed no in vitro activity.

Conclusion

Amphotericin B showed the most favorable in vitro inhibition of Fusarium species followed by natamycin, voriconazole and chlorhexidine, while 5-fluorocytosine, posaconazole, miconazole and caspofungin showed no relevant inhibiting effect. However, chlorhexidine showed fungicidal activity against 90% of F. oxysporum strains and 100% of the F. solani strains. Our study supports the clinical efficacy of chlorhexidine, and therefore warrants its further clinical evaluation for primary therapy of fungal keratitis, particularly in low and middle income countries where fungal keratitis is much more frequent and currently antifungal eye drops are often unavailable.