Title : The activity of PHMB and other guanidino containing compounds against Acanthamoeba
Abstract:
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), thereby identifying compounds that show potential for the treatment of microbial keratitis and for the inclusion in multi-purpose solutions (MPS). The study involved at first determining the minimum concentrations of these compounds against Acanthamoeba castellanii and Acanthamoeba polyphaga. Then using these concentrations, the rate of kill for these compounds against each organism was investigated using the time-kill method.
This study demonstrated that PHMG, PAPB, and guazatine are equal in activity to PHMB against Acanthamoeba trophozoites and cysts. All compounds demonstrated significant antimicrobial activity against trophozoites of both Acanthamoeba species resulting in a 2–2.6 log10 reduction in viability in comparison to the control (p < 0.001) at 6 h, which is the standard disinfection time for a contact lens solution. However, there was no significant difference between PHMB, PHMG, PAPB, and guazatine at this 6 h time point (p > 0.05), which proves and provides insight into the idea of guanidino compounds have similar and yet effective treatment against Acanthamoeba.
Audience take away:
o Through this research, the audience will become aware of amoebic parasite Acanthamoeba and the impact and correlation the parasite has with contact lenses. The blinding keratitis caused by Acanthamoeba, its incidence and research has been gaining traction through the years with ever growing use of contact lenses around the world. Unfortunately, there is not a standardized therapeutic scheme for the infections cause by Acanthamoeba keratitis. The risk factors being mostly with the use of contact lenses and the disinfection of them, and this research will show how to use compounds with specific chemical structures and whether incorporating them into multi-purpose solutions would be beneficial
o This research demonstrates that guanide containing compound have an effect on an amoebic parasite. For ophthalmologists, clinical researcher, pharmaceutical companies and contact lens companies, this might inspire to revisit the compounds that had had a different purpose at first and to observe if they can be incorporated into multi-purpose solutions (MPS) and affect real change in anti-microbial activity against existing parasitic or even bacterial and fungal eye infections.
o Yes, absolutely. The medical faculties could include this research into areas of parasitic infections of Acanthamoeba and similar infectious amoeba, such as the brain eating parasite Naegleria fowleri. The ophthalmology departments could benefit largely from this study’s findings, with the use of MPS for contact lenses being made aware of, and used correctly and safely. Additionally, this research focuses on the guanide or biguanide units of the compounds that were used to screen against Acanthamoeba, therefore could provide interest to Chemistry faculty. There are compounds that could be developed to have one or more biguanide units, such has Chlorhexidine, which has outstanding effectivity against oral bacteria. PHMB, a long standing treatment against Acanthamoeba, has painful side effects in patients. However, there are ample opportunities to find out if such compounds could be created with minimal to no side effects for the purpose of eye infection, considering that the eye is an extremely sensitive part of the body.
o Current treatments against Acanthamoeba include association of a biguanide (PHMB or chlorhexidine) with a diamidine (hexamidine or propamidine). This research provides insight into understanding what type of chemical structures have a better effect on parasitic infections, and rather than providing a treatment regime that have painful side effects, this study provides insight as to whether a singular treatment or prevention is possible. Acanthamoeba infections are worldwide, and not specific to regions. These parasites are resilient in nature, and so the need to develop disinfectants or treatment that deals with Acanthamoeba keratitis is urgent.
o The chemistry behind the making of contact lens disinfectants can be improved from this study, based on the idea that certain chemical structures or units have an anti-microbial effect. Differently structured compounds with the same units can be created with lesser side effect incorporated into their contact lens disinfectant solutions. Contact lenses have a huge market in which they require a standard combination of drugs in the disinfectant solutions. There is further research being carried within our group, into what other compounds can be used in the disinfectant solutions that also have an anti-microbial effect.
o Apart from testing against Acanthamoeba, this study also involved screening these drugs against a range of other ocular pathogens, including S. aureus and C. albicans, and we were able to observe a significant affect. Instead of offering a treatment regimen with unpleasant side effects, this research sheds light on what kinds of chemical structures have the most impact on parasitic, bacterial and parasitic infections. It also sheds light on whether a single treatment or prevention is feasible. Infections with Acanthamoeba can occur anywhere. Since these parasites have a tenacious nature, it is vital to create disinfectants or a treatment for Acanthamoeba keratitis. Based on this study’s hypothesis that specific chemical structures or units have an anti-microbial impact, the chemistry used to create contact lens disinfectants can be enhanced as a result of this work. Differently structured compounds with the same units can be made and added to contact lens disinfecting solutions with less negative effects.
