HYDROQUININE is a cinchona alkaloid and is found in the tree bark of the Dipterocarpaceae tree species (Stapleton et al, 2008; Alexandrakis et al, 2000). Antimicrobial and antioxidant properties are found in this type of bark extract. With high-performance liquid chromatography of resin extract samples, hydroquinine was most predominant from Dipterocarpus turbinatus and the entry to the bees’ nests (Vazirani et al, 2015; Mukhtar et al, 2022).
Various types of quinine derivatives have demonstrated benefits against malaria (Morgan et al, 2005). Of interest, hydroquinine was approved in 2020 for the treatment of nocturnal muscle cramps in the Netherlands (Wijma, 2020).
Hydroquinine has demonstrated variable levels of effectiveness against Staphylococcus aureus gram-positive bacteria and a variety of gram-negative bacteria. Hydroquinine was more effective in inhibiting growth of the multidrug resistant strain of Pseudomonas aeruginosa than that of the drug-sensitive strain. It is hypothesized that hydroquinine has a novel bacteriostatic mechanism of action against P. aeruginosa (Cope et al, 2015). Genes affecting virulence factors were downregulated, which reduced swarming motility.
HYDROQUININE & CONTACT LENSES
A recent study evaluated the disinfecting properties of hydroquinine combined with multipurpose solutions (MPSs) to block the adhesion of P. aeruginosa adhesion and biofilm formation (Weawsiangsang et al, 2024). P. aeruginosa is one of the common bacteria that cause contact lens-related corneal infections (microbial keratitis), with an estimated annualized incidence ranging from 2 to 20 cases per 10,000 wearers. Permanent vision loss may be the result of contact lens-related microbial keratitis (CLMK) (Fleiszig et al, 2020).
Prior studies have shown that disinfecting solutions were not effective in preventing biofilm formation (Weawsiangsang et al, 2024). A biofilm is developed on a colonized surface by microorganisms through adhesion to the surface and/or adhesion among the microorganisms. A biofilm may be a risk for developing a contact lens-related corneal infection.
A study investigated the anti-biofilm, antibacterial and anti-adhesion properties of MPS compared with hydroquinine-formulated MPS with soft contact lenses (Weawsiangsang et al, 2024). These hydrogel contact lenses are made from polymacon, with 2-hydroxyethyl methacrylate (HEMA) as the main monomer (58% HEMA and 42% water). The efficacy of two MPS solutions were evaluated. According to ISO 14729 criteria, both solutions were effective in preventing bacteria from standard and clinical P. aeruginosa strains. Hydroquinine reduced adhesion and anti-biofilm formation as demonstrated with RT-qPCR by directly influencing the expression levels of adhesion-related genes, specifically cgrC, cheY, cheZ, fimU, and pilV.
According to ISO testing, hydroquinine met the criteria of killing more than 99.9% of P. aeruginosa reference and clinical strains at the time of disinfection. The rates were more than 3 log of reduction, similar to MPSs. This study showed that the combination of MPSs and hydroquinine successfully inhibited P. aeruginosa adhesion and obliterated preexisting biofilms. A limitation of this study is that it only evaluated polymacon contact lenses. The disinfection efficacy of hydroquinine with various types of contact lenses would be beneficial.
An investigation of in vitro cytotoxicity studies of hydroquinine in human cell and in vivo animal models may offer beneficial information before human clinical trials. A possible future study may evaluate an in vitro model of real-world environmental conditions.
Incorporating hydroquinine-containing formulations with innovative natural ingredients as a disinfection solution for contact lenses may be a promising option for mitigating the risk of CLMK. These solutions may be beneficial in destroying biofilms.
REFERENCES
1. Stapleton F, Keay L, Edwards K, et al. The incidence of contact lens-related microbial keratitis in Australia. Ophthalmology. 2008 Oct;115:1655-1662.
2. Alexandrakis G, Alfonso EC, Miller D. Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones. Ophthalmology. 2000 Aug;107;1497-1502.
3. Mondino BJ, Weissman BA, Farb MD, Pettit TH. Corneal ulcers associated with daily-wear and extended-wear contact lenses. Am J Ophthalmol. 1986 Jul 15;102:58-65.
4. Vazirani J, Wurity S, Ali MH. Multidrug-resistant pseudomonas aeruginosa keratitis: Risk factors, clinical characteristics, and outcomes. Ophthalmology. 2015 Oct;122:2110-2114.
5. Mukhtar S, Atta S, Durrani A, Perera C, Kowalski R, Jhanji V. Microbiological evaluation of corneal and contact lens cultures in contact lens-associated bacterial keratitis. Br J Ophthalmol. 2022 May;106:600-604.
6. Morgan PB, Efron N, Hill EA, Raynor MK, Whiting MA, Tullo AB. Incidence of keratitis of varying severity among contact lens wearers. Br J Ophthalmol. 2005 Apr;89:430-436.
7. Wijma S. Hydroquinine (Inhibin®) for patients with nocturnal muscle cramps. The National Health Care Institute. 2020 March. Accessed 2024 April 8. Available at english.zorginstituutnederland.nl/publications/reports/2020/03/04/hydroquinine-inhibin-for-patients-with-nocturnal-muscle-cramps.
8. Cope JR, Collier SA, Rao MM, et al. Contact lens wearer demographics and risk behaviors for contact lens-related eye infections–united states, 2014. MMWR Morb Mortal Wkly Rep. 2015 Aug 21;64:865-870.
9. Weawsiangsang S, Rattanachak N, Ross S, et al. Enhances the Efficacy of Contact Lens Solutions for Inhibiting Pseudomonas aeruginosa Adhesion and Biofilm Formation. Antibiotics (Basel). 2024 Jan 5;13:56.
10. Fleiszig SMJ, Kroken AR, Nieto V, et al. Contact lens-related corneal infection: Intrinsic resistance and its compromise. Prog Retin Eye Res. 2020 May;76:100804.