In recent years, a rise in the number of contact lens users in the UK and worldwide coincided with an increased incidence of microbial keratitis. The aim of this study was to investigate the antimicrobial activities of polyhexamethylene guanidine (PHMG), polyaminopropyl biguanide (PAPB), and guazatine in comparison to the common contact lens disinfectant constituent, polyhexamethylene biguanide (PHMB). The study investigated these compounds against a broad range of organisms, including Acanthamoeba castellanii, Acanthamoeba polyphaga, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. This study demonstrated that PHMG, PAPB, and guazatine are equal in activity to PHMB against Acanthamoeba trophozoites and cysts. PHMG and PAPB are also equal in activity to PHMB against S. aureus and P. aeruginosa, whereas PHMG shows significantly better activity than PHMB against C. albicans (p < 0.001). To our knowledge, this is the first study to demonstrate the effectiveness of PHMB, PHMG, PAPB, and guazatine against Acanthamoeba and other ocular pathogens. As alternatives to PHMB, these compounds warrant further investigation for inclusion in contact lens solutions and for the treatment of keratitis.

Microbial keratitis, a vision-threatening infection commonly linked to contact lens use, poses a significant challenge, particularly when caused by Acanthamoeba species. Acanthamoeba keratitis (AK) is difficult to treat due to the organism’s ability to form resilient cysts, necessitating prolonged and complex therapeutic interventions. This study evaluated novel amidopropyl dimethylamines (APDs) and amidopropyl quaternary trimethylammoniums (APTs) for their antimicrobial efficacy against Acanthamoeba castellanii and Acanthamoeba polyphaga cysts. Minimum effective concentrations were determined, and time–kill assays assessed microbial inactivation over 24 h. The results indicated that certain APTs, particularly elaidamidopropyl trimethylammonium (EAPT) and oleamidopropyl trimethylammonium (OAPT), demonstrated superior cysticidal activity compared to the commercially used MAPD, achieving greater log reductions within 24 h (p < 0.0001) at a concentration of 25 µM. The enhanced efficacy of these compounds is potentially attributed to their unsaturated alkyl chains and positive charge, improving antimicrobial activity through the greater disruption of the Acanthamoeba cell membrane. These findings highlight the potential of APTs as alternative agents for incorporation into multipurpose lens disinfectants and AK treatment, offering improved disinfection efficacy. Further investigation is justified to optimise formulations for clinical and commercial applications.