In vitro activity of a novel compound, Mul-1867, against clinically significant fungi Candida spp. and Aspergillus spp

Abstract

There is an urgent need for new antifungal compounds to treat various types of fungal infections, including pulmonary infections. This study was designed to investigate the potency of a novel compound (Mul-1867) against Candida spp. and Aspergillus spp. isolated from patients with fungal pneumonia, cystic fibrosis and chronic obstructive pulmonary disease. Mul-1867 was highly effective against susceptible control strains as well as resistant clinical isolates, with minimum fungicidal concentrations (MFCs) varying from 0.06 microg/mL to 0.5 microg/mL. It was also highly effective against pre-formed 48-h-old biofilms formed by yeasts and moulds. The half-minimal biofilm eradication concentration (MBEC50) was equal to the MFC. The minimum biofilm eradication concentration to eliminate 90% of biofilms (MBEC90) varied from 1 x to 4 x MFC. Scanning electron microscopy revealed morphological changes accompanied by the release of intracellular material from the fungal cells following exposure to Mul-1867. Furthermore, an increased concentration of nucleic acids was found in the medium after 5 min and 20 min of Mul-1867 treatment, indicating leakage of cytoplasmic contents. Overall, these data indicate that Mul-1867 may be a promising inhaled antifungal agent for the treatment and prevention of fungal respiratory infections.