The combined utilization of Chlorhexidine and Voriconazole or Natamycin to combat Fusarium infections

Abstract

Background: 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. Results: We 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. Conclusions: Our 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.

Antifungal Activity of Minocycline and Azoles Against Fluconazole-Resistant Candida Species

“…As discussed previously ( Jiang et al, 2020 ), survival tests were conducted with sixth instar larvae (300 mg; Sichuan, China) to evaluate the efficacy of MIN as a single-agent and in combination with azole drugs on G. mellonella infected with C. albicans R14, C. parapsilosis N101, C. tropicalis 00279, C. glabrata 05448, and C. auris AR385. Larvae were stored in the dark at room temperature with shavings prior to experimental use, while Candida strains had been grown for 2 days on PDA, after which the colony surface was scraped with a sterile plastic loop, washed two times, and adjusted to 1 × 10 8 cfu/ml using sterile saline.…”

Fusarium Keratitis—Review of Current Treatment Possibilities

“…In clinical practice, chlorhexidine is probably more often concerned as an adjunctive therapy. One study reported good synergistic antifungal effects of CHX and VCZ, but not of CHX and NAT tested in vitro and in vivo ( G. mellonella model) on the F. solani and oxysporum strains collected from infected corneas, skin, nails, and auditory canals [ 103 ]. A pilot study from Uganda, in which CHX was used as a adjunctive therapy in recalcitrant fungal keratitis not responding to monotherapy with 5% NAT, among others, covered three cases of Fusarium spp.…”

Green chemistry principles for the synthesis of antifungal active gum acacia-gold nanocomposite - natamycin (GA-AuNC–NT) against food spoilage fungal strain Aspergillus ochraceopealiformis

“…The effect of natamycin on fungal corneal ulcers has been reported by Abhishakth Gerhardt et al, (2019). Jiang et al, (2020) reported synergistic antifungal activity of other antifungal drugs with natamycin against Fusarium sp. Natamycin induced antifungal action against plant pathogenic fungal strain Colletotrichum gloeosporioides has been studied by Liu et al, (2019).…”

“…The maximum cumulative release of 90.0 %, 94.1 %, 90.0 %, and 98.2 % was recorded at 144 h in distilled water, PBS, acetone, and ethanol. It can be seen that the initial burst release is an essential criterion of antifungal activity as it helps reach the therapeutic concentration of the drug in a minimal period, followed by constant release to maintain the sustained and controlled release of the drug (Jiang et al, 2020). Antifungal activity of natamycin released in the respective solvents at the respective period was evaluated against the fungal strain by well diffusion assay as described earlier.…”