In-vitro interaction of terbinafine alone and in combination against isolates of Aspergillus Species

Abstract

INTRODUCTION: The infection associated with Aspergillus species causes high morbidity and mortality in immunocompromised patients and the sudden outbreak of the COVID-19 pandemic worsened the situation in the healthcare system. Recent guidelines recommend the use of voriconazole and isavuconazole for the treatment of aspergillosis, but the emergence of Azole-resistant Aspergillus species limits the azole-based treatment approach. The use of antifungal combination therapy might become an emerging alternative strategy for aspergillosis. In our study, we evaluate the terbinafine interaction against Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus alone and in combination with other compounds.
MATERIAL AND METHODS: In-vitro terbinafine and other compounds activity against the Aspergillus species was assessed using the Disk Diffusion Assay and micro-broth dilution assay, and the Zone of Inhibition results were measured in millimetres with Mean ± Standard Deviation. The assessment of interaction was done by a chequerboard assay, and the interaction was quantified using the Fractional Inhibitory Concentration Index. These methods provide insights into the nature of the interaction, such as synergy, additivity, indifference, or antagonism.
RESULTS: The Zone of inhibition of terbinafine against Aspergillus strains ranges between 22.7±0.2 to 41.3±0.2, Ebselen 16.7±0.2 to 29.3±0.2, Amphotericin B 21.2±0.3 to 27.7±0.2, Aerosporine 6.1±0.2 to 12.5±0.2, Ciprofloxacin 6.3±0.3 and Gentamycin sulphate 6.2±0.2. Terbinafine and other compounds show variable activity and the interaction between these compounds is an interesting approach in the treatment of fungal infections.
CONCLUSION: The interaction between terbinafine and other compounds is interesting and might be a potential therapeutic approach against invasive Aspergillus infections.