Interaction Between Amorolfine and Voriconazole Against Fusarium species.

Qin Liu,Kaiping Zheng,Pin Liang,Si Jiang,Jiquan Song

doi:10.1007/s11046-021-00568-8

Qin Liu, Kaiping Zheng + Show 3 more

Open Access

https://doi.org/10.1007/s11046-021-00568-8

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Abstract

Fusarium species represent a range of fungal pathogens capable of causing diverse mycotic diseases. Relative to antibacterial drugs, few effective antifungal agents have been developed to date, and all are subject to significant limitations. As such, there is an urgent need to design novel antifungal treatments for infections caused by Fusarium spp. Herein, 15 clinical isolates, including 5 Fusarium oxysporum and 10 Fusarium solani strains, were analyzed to explore the relative inhibitory effects of different combinations of amorolfine (AMO) and voriconazole (VOR) on the growth of these fungal pathogens. These analyses were conducted by measuring minimal inhibitory concentration (MIC) values for these antifungal agents in a broth microdilution assay and by using an in vivo model of Fusarium-infected Galleria mellonella. These experiments revealed that in isolation, AMO and VOR exhibited MIC values ranging from 4 to 16μg/mL and 2 to 8μg/mL, respectively. However, these effective MIC values fell to 1-2μg/mL and 0.5-2μg/mL, respectively, when AMO and VOR were administered in combination with one another, exhibiting synergistic activity against 73.3% of analyzed Fusarium strains. Subsequent in vivo analyses conducted using the G. mellonella model further confirmed that combination VOR + AMO treatment was associated with significantly improved larval survival following Fusarium spp. infection. Together, these results serve as the first published evidence demonstrating that VOR and AMO exhibit synergistic activity against infections caused by Fusarium spp., indicating that they may represent an effective approach to antifungal disease treatment.

Highlights

Fusarium species are environmentally ubiquitous fungi capable of causing diverse superficial, locally invasive, or disseminated infections, making them important pathogens
This study is the first to demonstrate that voriconazole combined with amorolfine has a synergistic effect against Fusarium spp. infection and may be an effective method for antifungal therapy
A combination of amorolfine with voriconazole showed synergistic antifungal effects against 11 (73.3%) strains of Fusarium spp. and the effective Minimal inhibitory concentrations (MICs) ranges of amorolfine and voriconazole were primarily in the 1–2 μg/ml and 0.5–2 μg/ml ranges, respectively

Summary

Introduction

Fusarium species are environmentally ubiquitous fungi capable of causing diverse superficial, locally invasive, or disseminated infections, making them important pathogens. Fusarium species are environmentally ubiquitous fungi [1], and they are capable of inducing a range of diverse superficial, locally invasive, or disseminated infections [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]. Voriconazole or liposomal amphotericin B are the two primary drugs used to treat invasive fusariosis, and they are the most effective drugs for Fusarium infections [22,23,24]. As few novel antifungal drugs are available or in development, combination-based therapeutic approaches instead represent the most promising approach to treat serious fungal infections

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