PurposeTo limit corneal damage and potential loss of vision, bacterial keratitis must be treated aggressively. Innovation in antimicrobials is required due to the need for empirical treatment and the rapid emergence of bacterial resistance. Designed host defense peptides (dHDPs) are synthetic analogues of naturally occurring HDPs, which provide defense against invading pathogens. This study investigates the use of novel dHDPs for the treatment of bacterial keratitis.MethodsThe minimum inhibitory concentrations (MICs) were determined for dHDPs on both Gram-positive and -negative bacteria. The minimum biofilm eradication concentrations (MBEC) and in vitro time-kill assays were determined. The most active dHDP, RP444, was evaluated for propensity to induce drug resistance and therapeutic benefit in a murine Pseudomonas aeruginosa keratitis model.ResultsDesigned HDPs were bactericidal with MICs ranging from 2 to >64 μg/mL and MBEC ranging from 6 to 750 μg/mL. In time-kill assays, dHDPs were able to rapidly reduce bacterial counts upon contact with as little as 2 μg/mL. RP444 did not induce resistance after repeated exposure of P. aeruginosa to subinhibitory concentrations. RP444 demonstrated significant efficacy in a murine model of bacterial keratitis as evidenced by a significant dose-dependent decrease in ocular clinical scores, a significantly reduced bacterial load, and substantially decreased inflammatory cell infiltrates.ConclusionsInnovative dHDPs demonstrated potent antimicrobial activity, possess a limited potential for development of resistance, and reduced the severity of murine P. aeruginosa keratitis. These studies demonstrate that a novel dHDP may have potential to treat patients with sight-threatening bacterial keratitis.

Contact lens is a major risk factor for microbial keratitis among contact lens wearers. Chemical strategies that can prevent microbial adhesion and biofilm formation are required to improve a wearer’s hygiene and safety. Taking advantage of the material-independent properties of a polydopamine (pDA) coating, we investigated the role of covalent/noncovalent interactions of the antimicrobials and pDA in conferring long-term antimicrobial activities. The developed antimicrobial contact lenses not only retain their antibacterial efficiency against different bacterial strains for 2 weeks but also inhibit microbial adhesion and biofilm formation on the lens surfaces. The designed antimicrobial coatings were found to be safe for ocular cell lines. Moreover, the antimicrobial coatings did not affect the functional and surface properties of coated contact lenses. This methodology can be used to protect the contact lenses from microbial contamination for prolonged periods and has the potential to be extended for designing antimicrobial coatings for other medical devices as well.

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.

About a quarter of children with new onset of Kawasaki disease (KD) encounter coronary arterial involvement. While KD is known to cause vasculitis of medium-sized vessels, few studies have been done to study the involvement of the microcirculation. We aimed to investigate the association between coronary arterial dilatation and retinal microvasculature in a pilot setting, in order to further study the pathophysiological mechanism of KD from the perspective of small vessels changes. We performed a cross-sectional, observational, hospital-based study on 11 children aged 2 years and above with new-onset KD. Cardiac imaging technicians performed the echocardiographic examinations and recorded right coronary artery (RCA), left coronary artery (LCA) and left anterior descending artery (LAD). Qualified retinal graders reviewed and graded standardised retinal photographs to assess retinal microvascular parameters. Among 11 participants, there were 7 boys and 4 girls. Median and interquartile range of participants’ age were 5.92 (3.08) years. After adjusting for age and sex, each unit increase in LAD (mm) was significantly associated with increment of retinal arteriolar tortuosity (4.25 × 10−5 units, 95% Confidence Interval: 1.19, 7.32). Retinal arteriolar geometric changes were associated with LAD dilatation in 11 children with new onset of KD. Our pilot provided proof-of-concept that retinal imaging might be useful for detecting coronary arterial involvement in young children with KD and it needs further investigation.

Funding Acknowledgements Type of funding sources: None. Introduction Obstructive sleep apnoea (OSA) is associated with increased plaque burden in coronary artery disease (CAD), but the role of vascular inflammation in this relationship is unclear. Coronary computed tomography angiography (CTA) enables surrogate assessment of systemic inflammation via subcutaneous adipose tissue attenuation (ScAT-a), and of coronary inflammation via epicardial adipose tissue volume and attenuation (EAT-v and EAT-a) and pericoronary adipose tissue attenuation (PCAT-a). Purpose To investigate whether vascular inflammation is increased in patients with severe OSA and high plaque burden. Methods Patients with clinically indicated polysomnography and coronary CTA were included. Severe OSA was classified as apnoea/hypopnoea index (AHI) >30. High plaque burden was defined as a CT-Leaman score (CT-LeSc) >8.3. Patients with both severe OSA and high plaque burden were defined as ‘Group 1’, all other patients were classified as ‘Group 2’. ScAT-a, EAT-a, EAT-v and PCAT-a were assessed on semi-automated software. Results A total of 91 patients were studied (59.3 ± 11.1 years). Severe OSA was associated with high plaque burden (p = 0.02). AHI correlated with CT-LeSc (r = 0.24, p = 0.023). Group 1 had lower EAT-a and PCAT-a compared to Group 2 (EAT-a: -87.6 vs. -84.0 HU, p = 0.01; PCAT-a: -90.4 vs. -83.4 HU, p < 0.01). However, among patients without high plaque burden, EAT-a was increased in patients with severe OSA versus mild-moderate OSA (-80.3 vs. -84.0 HU, p = 0.020). On multivariable analysis, EAT-a independently associated with severe OSA and high plaque burden (p < 0.02), and PCAT-a associated with severe OSA and high plaque burden, and hypertension (all p < 0.01). Conclusions EAT attenuation is decreased in patients with severe OSA and high plaque burden but increased in patients with severe OSA and low plaque burden. These divergent results suggest coronary inflammation may be increased in OSA independent of CAD, but larger studies are required to validate these findings.