<i>In Vitro</i> Activity of Chlorhexidine Compared with Seven Antifungal Agents against 98 <i>Fusarium</i> Isolates Recovered from Fungal Keratitis Patients

Abstract

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 of infection 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 <i>Fusarium</i> keratitis is complex, and the optimal treatment is not well defined. We investigated the <i>in vitro</i> activity of chlorhexidine and seven antifungal agents against a well-characterized collection of <i>Fusarium</i> isolates recovered from patients with <i>Fusarium</i> keratitis. The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for <i>Fusarium</i> isolates that were cultured from cornea scrapings, ocular biopsy specimens, eye swabs, and contact lens fluid containers from patients with suspected keratitis. The <i>Fusarium</i> 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, 5-fluorocytosine, and caspofungin. In addition, the activity of chlorhexidine was determined. The fungal culture collection contained 98 <i>Fusarium</i> isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between 2007 and 2017. <i>Fusarium oxysporum</i> (<i>n</i> = 24, 24.5%) was the most frequently isolated species followed by <i>Fusarium solani</i><i>sensu stricto</i> (<i>n</i> = 18, 18.4%) and <i>Fusarium petroliphilum</i> (<i>n</i> = 11, 11.2%). Amphotericin B showed the most favorable <i>in vitro</i> inhibition of <i>Fusarium</i> 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 <i>F. oxysporum</i> strains and 100% of the <i>F. solani</i> 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.