Title : The potential of guanidino and amidopropyl dimethylamine compounds as topical treatments for diabetic foot ulcer infections
Diabetic foot ulcer (DFU) infections caused by multidrug resistant (MDR) organisms cost approximately 1% of the annual NHS budget, mainly through pre/post op management of complications/amputations. The aim of this study is to investigate the potential of guanidino based compounds and amidopropyl dimethylamines as repurposed topical treatments for DFU infections. Compounds from these groups have demonstrated a wide range of uses including antiseptics, antimalarial, antidiabetic and anticancer compounds. These compounds also demonstrate antimicrobial activity through disruption of the cellular membrane. The study investigated the activity of guanidino based and amidopropyl dimethylamine compounds against a broad range of MDR organisms including Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Candida albicans (C. albicans). This study has demonstrated that of the guanidino based compounds, polyhexamethylene guanidine (PHMG), polyaminopropyl biguanide (PAPB) and polyhexamethylene biguanide (PHMB) demonstrated significant activity against all the test organisms. PHMG, PHMB and PAPB demonstrated complete kill within 24 hours against S. aureus at 0.05 µg/ml and complete kill within 2 hours at 0.1 µg/ml against P. aeruginosa. PHMG demonstrated complete kill of C. albicans within 6 hours at 0.05 µg/ml. This study has also demonstrated that several amidopropyl dimethylamines demonstrate significant activity against the test organisms. Palmatamidopropyl dimethylamine (PAPD) at 7.8 µg/ml demonstrated complete kill within 1 hour against S. aureus and within 24 hours against C. albicans. PAPD and N,N-dimethylhexadecylamine demonstrated complete kill against P. aeruginosa within 4 hours and 2 hours respectively at 1 µg/ml. This study has demonstrated that guanidino based and amidopropyl dimethylamine compounds warrant further investigation for inclusion in the topical treatment of DFU infections.
Audience take away:
The audience will learn that gaunidino and amidopropyl dimethylamine compounds demonstrate activity against several MDR organisms including S. aureus, P. aeruginosa and C. albicans. Although this is framed in the setting of diabetic foot ulcer infection, these organisms are capable causing several other types of infection. Therefore, this study highlights such compounds for the potential use against a number of bacterial and fungal infections. The study also highlights that the length of the carbon chain attached to the functional group influences the antimicrobial activity of the compound. This information will be useful for those synthesizing similar compounds for potential treatment of bacterial and fungal infections.