Abstract
BackgroundFusarium species are the fungal pathogens most commonly responsible for the mycotic keratitis, which are resistant to the majority of currently available antifungal agents. The present study was designed to assess the efficacy of a combination of low doses chlorhexidine with two other commonly used drugs (voriconazole and natamycin) to treat Fusarium infections.ResultsWe utilized combinations of chlorhexidine and natamycin or voriconazole against 20 clinical Fusarium strains in vitro using a checkerboard-based microdilution strategy. In order to more fully understand the synergistic interactions between voriconazole and chlorhexidine, we utilized a Galleria mellonella model to confirm the combined antifungal efficacy of chlorhexidine and voriconazole in vivo. We found that for voriconazole, natamycin, and chlorhexidine as single agents, the minimum inhibitory concentration (MIC) ranges were 2–8, 4–16, and > 16 μg/ml, respectively. In contrast, the MIC values for voriconazole and chlorhexidine were reduced to 0.25–1 and 1–2 μg/ml, respectively, when these agents were administered in combination, with synergy being observed for 90% of tested Fusarium strains. Combined chlorhexidine and natamycin treatment, in contrast, exhibited synergistic activity for only 10% of tested Fusarium strains. We observed no evidence of antagonism. Our in vivo model results further confirmed the synergistic antifungal activity of chlorhexidine and voriconazole.ConclusionsOur results offer novel evidence that voriconazole and chlorhexidine exhibit synergistic activity when used to suppress the growth of Fusarium spp., and these agents may thus offer value as a combination topical antifungal treatment strategy.
Highlights
Fusarium species are the fungal pathogens most commonly responsible for the mycotic keratitis, which are resistant to the majority of currently available antifungal agents
Assessment of the in vivo antifungal activity of CHL and VOR in G. mellonella In order to evaluate the synergistic efficacy of CHL and VOR in vivo, we infected G. mellonella with F. solani Jsfs1 and treated these larvae using CHL and/or VOR
Oliveira et al found that CHL exhibited fungicidal activity against 90% of tested F. oxysporum strains and 100% of tested F. solani strains when evaluating 98 strains isolated from fungal keratitis patients [11]
Summary
Fusarium species are the fungal pathogens most commonly responsible for the mycotic keratitis, which are resistant to the majority of currently available antifungal agents. The present study was designed to assess the efficacy of a combination of low doses chlorhexidine with two other commonly used drugs (voriconazole and natamycin) to treat Fusarium infections. Single-agent VOR treatment has not been shown to be adequately protective as a means of treating some patients, suggesting that combination therapies may be necessary to achieve reliable and durable therapeutic efficacy [5]. Chlorhexidine (CHL) is an antiseptic agent that is commonly used and has been shown to be safe for ophthalmic exposure at concentrations of 1% or below [6]. The utility of CHL for treating keratomycosis, remains to be established
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