Purpose: To determine whether Mel4-coated antimicrobial contact lenses (MACLs) can reduce the incidence of corneal infiltrative events (CIEs) during extended wear. Methods: A prospective, randomized, double-masked, single-center, contralateral, extended contact lens wear clinical trial was conducted with 176 subjects. Each participant was randomly assigned to wear a MACL in one eye and an uncoated control contact lens in the contralateral eye or an extended-wear biweekly disposable modality for 3 months. The main outcome measures were the incidence of CIEs per 100 eye-months, identification of the microbial types colonizing the contact lenses or eyes at the time of the CIEs, and their susceptibility to Mel4. Results: Nine participants (5.1%) experienced unilateral CIEs; six participants had contact lens acute red eye, and three participants had infiltrative keratitis. The incidence rate for CIEs (0.4 events per 100 participant months; 1.7%) in the Mel4-coated lenses (test) was 69% less than that of the control lenses (1.3 events per 100 participant months; 3.4%; P = 0.29). All Gram-negative bacteria isolated from lenses and lids of participants with CIEs (Citrobacter diversus, Acinetobacter haemolyticus, and Acinetobacter lwoffii) were susceptible to Mel4 peptide; minimum inhibitory concentrations ranged from 15.6 to 62.5 µg/mL. Reduction of adhesion of these bacteria by Mel4-coated lenses ranged from 2.1 to 2.2 log₁₀ colony-forming units/lens. Conclusions: MACLs had the capacity to reduce CIEs by at least 50% compared with uncoated control lenses during extended wear over 3 months; however, due to the relatively low rates of CIEs, the reduction was not statistically different compared with control lenses. Translational Relevance: This study provides evidence that antimicrobial contact lenses have the potential to reduce the incidence of corneal infiltrative events during extended wear.

(1) Background: Essential oils (EOs) have emerged as promising antibacterial agents due to their broad-spectrum activity and low risk of resistance development. Therefore, this review aimed to assess the effectiveness of EOs against Gram-positive ESKAPE pathogens, and to evaluate their safety and toxicity in mammalian cells. (2) Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science. (3) Results: Heracleum pyrenaicum exhibited the most potent effect, with a MIC of 0.02–0.04 µg/mL and a selectivity index ranging from 251.3 to 2006.5, indicating high selective toxicity toward bacterial cells over mammalian cells. In contrast, certain species such as Cannabis sp. and Citrus sp. had selectivity indices of <1, indicating toxicity to mammalian cells. Ocimum basilicum showed good efficacy against methicillin-resistant S. aureus (MRSA), with a selectivity index of 23.4–34.9, while Satureja nabateorum demonstrated potent activity against E. faecium, with a selectivity index of 65.6–87.2. (4) Conclusions: EOs from Heracleum, Eucalyptus, Cinnamomum, Mentha, Thymus, and Syzygium aromaticum had good efficacy and high safety margins and show a potential for development for treating Gram-positive ESKAPE pathogen infections. However, EOs with a narrow safety margin (selectivity index < 10) raise concerns and warrant further in vivo and clinical trials to better understand their therapeutic windows and potential adverse effects.

Background: Novel therapeutic compounds with strong efficacy and low resistance potential are urgently needed to combat life-threatening infections caused by antibiotic-resistant ESKAPEE pathogens. These pathogens contribute globally to a large share of bloodstream, respiratory, urinary, and wound infections, and often have levels of high antimicrobial resistance. This review examined the antimicrobial efficacy of different plant essential oils (EOs) against Gram-negative ESKAPEE pathogens and their cytotoxic effects and calculated selectivity indices in cancer and normal cell lines. Methods: This review was developed using studies retrieved from PubMed, Scopus, and Web of Science, covering publications between 2013 and 2024 using the search terms: “essential oils”, “plant extracts”, “safety”, “cytotoxicity”, “cell lines”, “human”, “in-vitro”, antimicrobial”, “antibacterial” and “antibiotic” with Boolean operators (“AND”, “OR”, “NOT”). Only studies that reported both antimicrobial inhibitory concentrations and concentrations causing toxicity to mammalian cells were included in the final review. These data were then used to calculate the selectivity indices of the EOs (toxic concentration/antimicrobial inhibitory concentration) to give an initial assessment of safety. Results: Ocimum basilicum EOs had strong antibacterial effects against the Gram-negative ESKAPEE pathogens Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, with minimum inhibitory concentrations (MICs) as low as 1 μg/mL and high selectivity indices of >80.4. Likewise, Satureja nabateorum EOs had potent antibacterial activity, with a low MIC of 0.1 μg/mL against K. pneumoniae, 2.3 μg/mL against E. coli, and 12.5 μg/mL against P. aeruginosa, along with a very high selectivity index (>100). Other EOs such as those from Eucalyptus spp., Thymus spp., Mentha spp., Cinnamomum spp., Artemisia spp., and Aquilaria crassna also had broad-spectrum antibacterial potential and minimal toxicity toward mammalian cells, making them promising candidates for safe and effective antimicrobial agents in clinical and industrial applications. However, several EOs had selectivity indices of <10, indicating that at their MIC they would also be potentially highly cytotoxic. EOs tended to show increased toxicity to cells derived from cancers. Conclusions and recommendations: Certain EOs are highly active against Gram-negative ESKAPEE pathogens. They are also toxic to cancer-derived mammalian cells. Additional studies using normal cell lines and clinical trials are warranted to further validate their safety and therapeutic potential.

Transmission of pathogens present in the indoor air can occur through aerosols. This study evaluated the efficacy of an evaporated mix of essential oils to reduce the numbers of culturable aerosolized coronavirus, bacterium and fungus. The essential oil-containing gel was allowed to vaporize inside a glass chamber for 10 or 20 min. Aerosols of a surrogate of SARS-CoV-2, murine hepatitis coronavirus MHV-1, Escherichia coli or Aspergillus flavus spores were produced using a collision nebuliser and passed through the essential oil vapours, then collected on a six-stage Andersen sampler. The six-stages of the impact sampler capture aerosols in sizes ranging from 7 to 0.65 µm. The number of culturable microbes present in the aerosols collected in the different stages were enumerated and compared to the number of culturable microbes in control microbial aerosols that were not exposed to the evaporated essential oils. After 10 and 20 min evaporation, the essential oils reduced the numbers of culturable aerosolized coronavirus by 48% (log₁₀ reduction = 0.3; p = 0.002 vs. control) and 53% (log₁₀ reduction = 0.3; p = 0.001 vs. control), respectively. The essential oils vaporised for 10 min, reduced the number of viable E. coli by 51% (log₁₀ reduction = 0.3; p = 0.032 vs. control). The Aspergillus flavus spores were mostly observed in the larger aerosols (7.00 µm to 2.10 µm) and the essential oils vaporised for 10 min reduced the number of viable spores by 72% (log₁₀ reduction = 0.6; p = 0.008 vs. control). The vapours produced by a gel containing naturally occurring essential oils were able to significantly reduce the viable numbers of aerosolized coronavirus, bacteria and fungal spores. The antimicrobial gel containing the essential oils may be able to reduce aerosol transmission of microbes when used in domestic and workplace settings.

A clinical study of antimicrobial contact lenses containing the cationic peptide Mel4 was conducted. The few adverse events that occurred with this lens occurred on or after 13 nights of wear. The current study examined whether the Mel4 contact lenses lost activity during wear and the mechanism of this loss. Participants wore contact lenses for up to 13 nights. Lenses were tested for their ability to reduce the adhesion of Pseudomonas aeruginosa and Staphylococcus aureus. The amount of protein and lipid extracted from lenses was measured. The ability of trypsin to affect the antimicrobial activity of Mel4-coated contact lenses was measured. Mel4-coated contact lenses lost their antimicrobial activity at six nights of wear for both bacteria. The amount of lipids (13 ± 11 vs. 21 ± 14 μg/lens at 13 nights wear) and proteins (8 ± 4 vs. 10 ± 3 mg/lens at 13 nights of wear) extracted from lenses was not different between Mel4-coated and uncoated lenses, and was not different after three nights when antimicrobial activity was maintained and thirteen nights when they had lost activity (lipid: 25 ± 17 vs. 13 ± 11, p = 0.2; protein: 8 ± 1 vs. 8 ± 4 mg/lens, p = 0.4). Trypsin digestion eliminated the antimicrobial activity of Mel4-coated lenses. In summary, Mel4-coated contact lenses lost antibacterial activity at six nights of wear, and the most likely reason was proteolytic digestion of the peptide. Future studies will design and test proteolytically stable peptide mimics as coatings for contact lenses.