Inhibitory effect of host ocular microenvironmental factors on chlorhexidine digluconate activity

Chun-Hsien Chen; Yu-Jen Wang; Jian-Ming Huang; Fu-Chin Huang; Wei-Chen Lin

doi:10.1128/AAC.02066-20

Inhibitory effect of host ocular microenvironmental factors on chlorhexidine digluconate activity

Antimicrob Agents Chemother. 2023 May 1;65(5):e02066-20. doi: 10.1128/AAC.02066-20. Epub 2021 Mar 8.

Authors

Chun-Hsien Chen¹, Yu-Jen Wang¹, Jian-Ming Huang², Fu-Chin Huang³, Wei-Chen Lin^{4

2

5}

Affiliations

¹ Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Department of Parasitology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan wcnikelin@mail.ncku.edu.tw.
⁵ Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

Acanthamoeba spp. are free-living protozoan that cause a serious human eye disease called Acanthamoeba keratitis (AK). Several new and effective medical therapy for AK patients remains highly debated and therefore, CHG is still considered one of the first lines of treatment for AK patients. We hypothesized that ocular microenvironmental factors are responsible for Acanthamoeba drug resistance and clinical AK treatment failure. To investigate the influence of the ocular surface on CHG treatment, we tested the effect of several ocular elements on the anti-amoeba activity of CHG. The suspected inhibitory elements, including mucin, albumin, human and amoeba cell lysates, live and heat-killed bacteria, and cornea, were added to the amoebicidal activity platform, where amoeba was incubated with CHG at varying concentrations. Mucin showed a significant inhibitory effect on CHG activity against Acanthamoeba castellanii In contrast, albumin did not affect CHG treatment. Furthermore, human and amoeba cell lysates as well as live and heat-killed bacterial suspensions also significantly inhibited CHG activity. Additionally, we found that pig corneas also reduced CHG activity. In contrast, dry eye drops and their major component, propylene glycol, which is commonly used as eyewash material, did not have an impact on CHG activity. Our results demonstrate the effect of ocular microenvironmental factors on CHG activity and suggest that these factors may play a role in the development of amoeba resistance to CHG and treatment failure.