Antimicrobial resistance is a critical global challenge in the 21st century, validating Sir Alexander Fleming’s warning about the misuse of antibiotics leading to resistant microbes. With a dwindling arsenal of effective antibiotics, it is imperative to concentrate on alternative antimicrobial strategies. Previous studies have not comprehensively discussed the advantages and limitations of various strategies, including bacteriophage therapy, probiotics, immunotherapies, photodynamic therapy, essential oils, nanoparticles and antimicrobial peptides (AMPs) within a single review. This review addresses that gap by providing an overview of these various non-antibiotic antimicrobial strategies, highlighting their pros and cons, with a particular emphasis on antimicrobial peptides (AMPs). We explore the mechanism of action of AMPs against bacteria, viruses, fungi and parasites. While these peptides hold significant promise, their application in mainstream drug development is hindered by challenges such as low bioavailability and potential toxicity. However, advancements in peptide engineering and chemical modifications offer solutions to enhance their clinical utility. Additionally, this review presents updates on strategies aimed at improving the cost, stability and selective toxicity of AMPs through the development of peptidomimetics. These molecules have demonstrated effective activity against a broad range of pathogens, making them valuable candidates for integration into surface coatings to prevent device-associated infections. Furthermore, we discuss various approaches for attaching and functionalising these peptides on surfaces. Finally, we recommend comprehensive in vivo studies to evaluate the efficacy of AMPs and their mimetics, investigate their synergistic combinations with other molecules and assess their potential as coatings for medical devices.

Background: Ocular infections caused by antibiotic-resistant pathogens can result in partial or complete vision loss. The development of pan-resistant microbial strains poses a significant challenge for clinicians as there are limited antimicrobial options available. Synthetic peptoids, which are sequence-specific oligo-N-substituted glycines, offer potential as alternative antimicrobial agents to target multidrug-resistant bacteria. Methods: The antimicrobial activity of synthesised peptoids against multidrug-resistant (MDR) ocular pathogens was evaluated using the microbroth dilution method. Hemolytic propensity was assessed using mammalian erythrocytes. Peptoids were also incubated with proteolytic enzymes, after which their minimum inhibitory activity against bacteria was re-evaluated. Results: Several alkylated and brominated peptoids showed good inhibitory activity against multidrug-resistant Pseudomonas aeruginosa strains at concentrations of <= 15 mu g mL(-1 )(<= 12 mu M). Similarly, most brominated compounds inhibited the growth of methicillin-resistant Staphylococcus aureus at 1.9 to 15 mu g mL(-1) (12 mu M). The Nterminally alkylated peptoids caused less toxicity to erythrocytes. The peptoid denoted as TM5 had a high therapeutic index, being non-toxic to either erythrocytes or corneal epithelial cells, even at 15 to 22 times its MIC. Additionally, the peptoids were resistant to protease activity. Conclusions: Peptoids studied here demonstrated potent activity against various multidrug-resistant ocular pathogens. Their properties make them promising candidates for controlling vision-related morbidity associated with eye infections by antibiotic-resistant strains.

The rapid emergence of drug-resistant bacteria is a major global health concern. Antimicrobial peptides (AMPs) and peptidomimetics have arisen as a new class of antibacterial agents in recent years in an attempt to overcome antibiotic resistance. A library of phenylglyoxamide-based small molecular peptidomimetics was synthesised by incorporating an N-alkylsulfonyl hydrophobic group with varying alkyl chain lengths and a hydrophilic cationic group into a glyoxamide core appended to phenyl ring systems. The quaternary ammonium iodide salts 16d and 17c showed excellent minimum inhibitory concentration (MIC) of 4 and 8 μM (2.9 and 5.6 μg/mL) against Staphylococcus aureus, respectively, while the guanidinium hydrochloride salt 34a showed an MIC of 16 μM (8.5 μg/mL) against Escherichia coli. Additionally, the quaternary ammonium iodide salt 17c inhibited 70% S. aureus biofilm formation at 16 μM. It also disrupted 44% of pre-established S. aureus biofilms at 32 μM and 28% of pre-established E. coli biofilms 64 μM, respectively. A cytoplasmic membrane permeability study indicated that the synthesised peptidomimetics acted via disruption and depolarisation of membranes. Moreover, the quaternary ammonium iodide salts 16d and 17c were non-toxic against human cells at their therapeutic dosages against S. aureus.

Previous studies have demonstrated that contact lenses coated with the antimicrobial cationic peptide Mel4, a derivative of melimine, can reduce the occurrence of keratitis. However, the antimicrobial activity of Mel4 weakened over time due to its susceptibility to proteolytic degradation. Oligo-N-substituted glycine peptoids such as TM5 and TM18 possess antimicrobial properties and are resistant to proteolytic breakdown. This study focused on exploring methods for covalently attaching these peptoids to contact lenses to enhance their durability and performance in vitro. The peptoids TM5 and TM18 were covalently attached to etafilcon lenses via carbodiimide chemistry (EDC/NHS), oxazoline plasma, and plasma ion immersion implantation (PIII). The lenses were analysed using X-ray photoelectron spectroscopy (XPS), surface charge, and hydrophobicity. Inhibition of adhesion of multidrug-resistant Pseudomonas aeruginosa and cytotoxicity on corneal epithelial cells were evaluated. The impact of moist heat sterilization on activity was also assessed. XPS confirmed peptoid binding to lenses. Peptoid coatings slightly increased contact angles (≤23°) without affecting overall charge. Peptoids, bound via carbodiimide, inhibited P. aeruginosa adhesion by over 5 log10 CFU per lens, outperforming melimine, which required six times the concentration for a 3 log10 reduction. Peptoids attached via oxazoline or PIII reduced adhesion by > 5 log10 CFU. All covalent methods significantly reduced bacterial adhesion compared to untreated lenses (P < 0.0001). Peptoid-bound lenses were non-toxic to corneal epithelial cells. Sterilization did not affect carbodiimide-treated lenses but reduced the activity of oxazoline and PIII surfaces by 1-2 log10 CFU. Peptoids TM5 and TM18 effectively reduced P. aeruginosa adhesion on lenses, with carbodiimide-bound surfaces retaining activity post-sterilization, showing promise for the development of antimicrobial contact lenses.

This study examines the incidence of infection and resistance associated with Intracorneal Ring Segment (ICRS) implantation, a common outpatient surgical treatment for correcting refractive errors and corneal ectatic diseases. Although ICRS procedures are typically safe and reversible, there is a low but notable risk of microbial infections, which require prompt and sometimes invasive treatment. Three electronic databases, PubMed, Web of Science (WoS), and Scopus, were utilised to search for literature according to PRISMA guidelines to identify infections related to the implantation of ICRS in the cornea between January 2000 and December 2022. Gram-positive organisms were involved in 86% of cases: 35.7% S. aureus, 25% coagulase-negative staphylococci species, 17.8% streptococci and 7.1% Nocardia species. Less commonly recorded were Gram-negative bacteria (14%), with Pseudomonas aeruginosa (circa 10%) and Klebsiella pneumonia (4%) being the most common Gram-negative bacteria. In rare cases, fungi have also been reported. ICRS-related bacterial infections can be categorised into early or late onset. Early onset infection typically manifests within the first few weeks after implantation and is often associated with contamination during surgery, unhygienic practices, or inadequate sterilisation techniques. On the other hand, late-onset infection may develop months or even years after the initial procedures and may be associated with persistent bacterial colonisation, secondary infections, or prolonged use of prophylactic antibiotics. S aureus is encountered in both early and late-onset infections, while Nocardia species and K. pneumoniae have generally been reported to occur in late-onset infections. In addition, vision recovery from S. aureus infections tends to be poor compared to other bacterial infections. S. aureus is a predominant pathogen that often requires surgical intervention with poor outcomes. Early infections result from incision gaps and ring segment rubbing, while late infections are linked to prolonged antibiotic use. Further research is needed on novel antimicrobial ICRS to procure the vision.

The advancement of antimicrobial contact lenses presents a promising strategy for mitigating microbial keratitis. This study investigated the antimicrobial activity of four guanidine-substituted anthranilic amide peptidomimetics (GAMPs), identifying RK1083 as the most potent candidate. The minimum inhibitory concentrations ranged from 20 to 86 µM, with therapeutic indices between 2 and 22. All tested GAMPs exhibited resistance to proteolytic degradation. RK1083 was covalently immobilized onto contact lenses using carbodiimide chemistry, oxazoline plasma deposition, and plasma immersion ion implantation (PIII). The modified lenses demonstrated increased nitrogen content (≥3%), changes in surface charge, and improved hydrophilicity. Adhesion of Staphylococcus aureus was reduced by 5 log₁₀, while Pseudomonas aeruginosa adhesion decreased by ≥5 log₁₀ on oxazoline and PIII-treated lenses, and by ≥3 log₁₀ on carbodiimide-treated lenses. RK1083-coated surfaces exhibited no cytotoxicity toward corneal epithelial cells, and carbodiimide-treated lenses maintained antimicrobial activity post-sterilization. These results underscore RK1083’s potential for enhancing antimicrobial contact lens surfaces with improved bacterial resistance.