Unexpected activity of p-bromo-domiphen, a new quaternary ammonium compound, against Candida auris

Introduction- Candida auris has the ability to persistently colonize hospital environments, with the propensity for transmission in health care settings, and to survive for weeks on plastics, fabrics, and nonporous surfaces. Cationic agents are an important class of anti-infectives widely used for environmental infection control. In particular, quaternary ammonium compounds (QACs) are largely recognized as antiseptics and disinfectants. Nevertheless, commonly used QACs seem to be ineffective against C. auris. The aim of the present study was to assess the efficacy of the new QAC p-bromo-domiphen, a derivative of domiphen, in inhibiting C. auris adhesion and growth. Materials and Methods- We assessed the antimicrobial activity of both domiphen (D) and bromiphen (p-bromo-domiphen, Br-D, patent numbers WO2019053626 and PCT/IB2018/057007) against several Candida species, including C. auris. Benzalkonium chloride was used as reference QAC. Minimal inhibitory concentrations (MICs) were evaluated using EUCAST protocol for yeasts. Compounds activity was also tested on C. auris biofilms by measuring biomass reduction. Cytotoxicity was performed on mammalian cells (HEp-2 ATCC CCL-23) by MTT assay, and in the invertebrate model Galleria mellonella by directly injecting various drug concentrations into the haemocoel. Results- Compared to the parental compound domiphen bromide, bromiphen namely p-bromo-domiphen bromide, resulted more active in all the performed tests. In particular, planktonic MIC90 for C. auris were 8 mg/L and 2 mg/L for D and Br-D, respectively. Concerning the cytotoxicity, the IC50 (a concentration that causes a reduction by half of the activity of mitochondrial dehydrogenase) were 10 mg/L for Br-D and 7 mg/L for D. Selectivity index (SI) values were 0.8 for D and 5 for Br-D. Doses up to 8 mg/L of both compounds were nontoxic to G. mellonella larvae. Discussion- The environment of patients colonized or infected with C. auris can become heavily contaminated. Our preliminary data suggest that bromiphen is a promising QAC for environmental and possible skin decontamination against C. auris persistence.