Research articleA new ophthalmic formulation containing antiseptics and dexpanthenol: In vitro antimicrobial activity and effects on corneal and conjunctival epithelial cells
Introduction
Antimicrobial resistance to antibiotics is one of the biggest public health challenges of our time and it has been continuously increasing in recent years, even in ocular pathogens (Asbell and DeCory, 2018; Bertino, 2009; Holland et al., 2014). As in all human infections, the rise of bacterial resistance can also be of concern in ophthalmology, leading to unsuccessful treatment of sight-threatening infections (Asbell and DeCory, 2018; Bertino, 2009; Holland et al., 2014).
Since the overuse of antibiotics in the treatment of ocular infectious diseases has led to the appearance of multidrug-resistant bacterial strains (Asbell and DeCory, 2018), the interest towards antiseptics is growing. In ophthalmology, the role of topical antibiotics in the prophylaxis of post-surgical endophthalmitis, especially in intravitreal injections, is under debate because their perioperative use can increase the resistance of conjunctival flora but has no proven added effectiveness in preventing endophthalmitis if combined with povidone iodine antisepsis (Grzybowski et al., 2017).
Moreover, due to their wide spectrum of activity (multi-drug resistant bacteria, methicillin-resistant staphylococcus aureus, viruses, protozoa, fungi) (Grzybowski et al., 2018; Kaehn, 2010; Maycock and Jayaswal, 2016), and the few reports on reduced microbial susceptibility which currently only concern chlorhexidine (Horner et al., 2012; Kampf, 2016), the use of antiseptics has been proposed for the treatment of viral conjunctivitis, mild bacterial conjunctivitis, or even more severe infections (such as keratitis) in developing countries, where the availability of antibiotics is often limited by costs (Grzybowski et al., 2018; Isenberg et al., 2017). Regarding Acanthamoeba keratitis, the only available treatment are the antiseptics biguanides (PHMB 0.02%, and chlorhexidine 0.02%) and diamidines (hexamidine 0.1% or propamidine 0.1%) (Carrijo-Carvalho et al., 2017; Maycock and Jayaswal, 2016).
However, antiseptics may be toxic for the ocular surface epithelia, leading to corneal epithelial defects or damage, especially at high concentrations (Shibata et al., 2014). Therefore, there is an increasing interest in topical formulations containing antiseptics with a wide antimicrobial spectrum, but with a lower tendency to damage the ocular surface. Recently, an ophthalmic solution containing antiseptics, such as hexamidine diisethionate 0.05%, PHMB 0.0001%, disodium edetate (EDTA) 0.01%, and healing agents, such as dexpanthenol (D-panthenol)5% and polyvinyl alcohol 1.25%, has been launched on the market in Italy (Keratosept, Bruschettini, Genova, Italy). The purposes of our study were to evaluate the antimicrobial activity of this product on isolates of Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus mitis, that are among the most frequent causes of ocular infections (Asbell and DeCory, 2018; Garg et al., 2017; Green et al., 2008; Han et al., 1996; Teweldemedhin et al., 2017) and to analyze in vitro the effects of this solution and of its components on cultured human corneal and conjunctival cells.
Section snippets
In vitro antimicrobial activity of the ophthalmic solution
The antimicrobial activity of the ophthalmic solution was evaluated using a modified protocol from the International Organization for Standardization- ISO 14729 guidelines (International Organization for Standardization, 2001).
Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus mitis (of the Viridans Group Streptococci, VGS) were used in this study. All the microbial strains were
In vitro antimicrobial activity of the ophthalmic solution
The Keratosept ophthalmic solution showed an antiseptic spectrum of activity and gave an average log reduction of 2.14 ± 0.35 within 6 h of exposure, significantly higher than the control solution (p-value < 0.05), although individual log reductions varied between microorganisms (Fig. 1). Log reductions of the fastidious species (Streptococcus pneumoniae, Streptococcus mitis and Streptococcus pyogenes) were significantly marked within 2 h of exposure to the ophthalmic solution (p-value < 0.05
Discussion
Increasing trends in antibiotic resistance in ocular infections, especially widespread fluoroquinolone non-susceptibility (Asbell and DeCory, 2018; Bertino, 2009; Holland et al., 2014), have enhanced the role of antiseptics in the prevention of infection after ocular surgery (Grzybowski et al., 2017). Nowadays, povidone-iodine (PVI) and chlorhexidine represent the elective antiseptics in ophthalmology. However, a reduced susceptibility to chlorhexidine of MRSA and other staphylococci was
Funding declaration
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
None.
References (35)
- et al.
Therapeutic agents and biocides for ocular infections by free-living amoebae of Acanthamoeba genus
Surv. Ophthalmol.
(2017) - et al.
Spectrum and susceptibilities of microbiologic isolates in the endophthalmitis vitrectomy study
Am. J. Ophthalmol.
(1996) - et al.
Antibiotic resistance in acute postoperative endophthalmitis
Ophthalmology
(2014) - et al.
Prospective, randomized clinical trial of povidone-iodine 1.25% solution versus topical antibiotics for treatment of bacterial keratitis
Am. J. Ophthalmol.
(2017) Acquired resistance to chlorhexidine - is it time to establish an 'antiseptic stewardship' initiative?
J. Hosp. Infect.
(2016)- et al.
Povidone-iodine concentration and dosing in cataract surgery
Surv. Ophthalmol.
(2018) - et al.
Chitosan coated human serum albumin nanoparticles: a promising strategy for nose-to-brain drug delivery
Int. J. Biol. Macromol.
(2019) - et al.
Evaluation of povidone-iodine as a disinfectant solution for contact lenses: antimicrobial activity and cytotoxicity for corneal epithelial cells
Contact Lens Anterior Eye
(2006) - et al.
Antibiotic resistance among bacterial conjunctival pathogens collected in the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study
PloS One
(2018) - et al.
Film dressings based on hydrogels: simultaneous and sustained-release of bioactive compounds with wound healing properties
Pharmaceutics
(2019)
Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics
Clin. Ophthalmol.
Successful treatment of Acanthamoeba keratitis by hexamidine
Cornea
EDTA: an antimicrobial and antibiofilm agent for use in wound care
Adv. Wound Care
Polyhexanide – safety and efficacy as an antiseptic
Tidsskr. Nor. Laegeforen.
Endophthalmitis after cataract surgery: epidemiology, risk factors, and evidence on protection
Curr. Opin. Ophthalmol.
Risk factors and causative organisms in microbial keratitis
Cornea
Microbial flora and resistance in ophthalmology: a review
Graefes Arch. Clin. Exp. Ophthalmol.
Cited by (16)
Co-expression of the SARS-CoV-2 entry receptors ACE2 and TMPRSS2 in healthy human conjunctiva
2021, Experimental Eye ResearchCorneal wound healing—Pharmacological treatment
2024, OphthalmologieActivHeal® PHMB Foam dressing range: a product evaluation
2024, Wounds UKAcute Corneal Melting Induced by the Concomitant Use of a Non-steroidal Anti-inflammatory Agent with an Antiseptic Eye Drop
2024, Ophthalmology and TherapyDry Eye Disease in the Middle East and Northern Africa: A Position Paper on the Current State and Unmet Needs
2024, Clinical Ophthalmology
- 1
These authors contributed equally to this work.