22The rise in antimicrobial resistance has prompted the development of alternatives, 23 such as plant-derived compounds, to combat bacterial infections. Bald's eyesalve, a 24 remedy used in the Early Medieval period, has previously been shown to have efficacy 25 against Staphylococcus aureus grown in an in vitro model of soft tissue infection. This 26 remedy also had bactericidal activity against methicillin-resistant S. aureus (MRSA) in 27 a chronic mouse wound. However, the safety profile of Bald's eyesalve has not yet 28 been demonstrated, and this is vital before testing in humans. Here, we determined 29 the safety potential of Bald's eyesalve using in vitro, ex vivo, and in vivo models 30 representative of skin or eye infections. We also confirmed that Bald's eyesalve is 31 active against an important eye pathogen, Neisseria gonorrhoeae. Low levels of 32 cytotoxicity were observed in eyesalve-treated cell lines representative of skin and 33 immune cells. Results from a bovine corneal opacity and permeability test 34 demonstrated slight irritation to the cornea that resolved within 10 minutes. The slug 35 mucosal irritation assay revealed that a low level of mucus was secreted by slugs 36 exposed to eyesalve, indicating mild mucosal irritation. We obtained promising results 37 from mouse wound closure experiments; no visible signs of irritation or inflammation 38 were observed. Our results suggest that Bald's eyesalve could be tested further on 39 human volunteers to assess safety for topical application against bacterial infections. 40 41 Importance: Alternative treatment for bacterial infections are needed to combat the 42 ever increasing repertoire of bacteria resistant to antibiotics. A medieval plant-based 43 remedy, Bald's eyesalve, shows promise as a substitute for the treatment of these 44infections. For any substance to be effective in the treatment of bacterial infections in 45 humans, it is important to consider the safety profile. This is a key consideration in 46 3 order to have the necessary regulatory approval. We demonstrate the safety profile of 47 Bald's eyesalve using a variety of models, including whole-organ and whole-animal 48 models. Our results show that Bald's eyesalve is mildly toxic to cultured human cells, 49 but potentially suitable for patch tests on healthy human volunteers to assess safety 50 for later clinical trials. Our work has the potential to transform the management of 51 diseases caused by bacterial infections, such as diabetic foot ulcers, through topical 52 application of a natural product cocktail based on Bald's eyesalve. 53 54
The rise in antimicrobial resistance has prompted the development of alternatives to combat bacterial infections. Bald’s eyesalve, a remedy used in the Early Medieval period, has previously been shown to have efficacy against Staphylococcus aureus in in vitro and in vivo models of chronic wounds. However, the safety profile of Bald’s eyesalve has not yet been demonstrated, and this is vital before testing in humans. Here, we determined the safety potential of Bald’s eyesalve using in vitro, ex vivo, and in vivo models representative of skin or eye infections. We also confirmed that Bald’s eyesalve is active against an important eye pathogen, Neisseria gonorrhoeae. Low levels of cytotoxicity were observed in eyesalve-treated cell lines representative of skin and immune cells. Results from a bovine corneal opacity and permeability test demonstrated slight irritation to the cornea that resolved within 10 min. The slug mucosal irritation assay revealed that a low level of mucus was secreted by slugs indicating moderate mucosal irritation. We obtained promising results from mouse wound closure experiments; no visible signs of irritation or inflammation were observed. Our results suggest that Bald’s eyesalve could be tested further on human volunteers to assess safety for topical application against bacterial infections.
Introduction: Ophthalmia neonatorum is a severe, sight-threatening condition that occurs in neonates worldwide. Etiological factors include chemical agents, viruses, and bacteria, such as Neisseria gonorrhoeae and Chlamydia trachomatis acquired from infected mothers at birth. Prevalence varies geographically, depending upon socioeconomic conditions, maternal health care, and prophylactic treatments available. Antibiotic resistance, particularly in N. gonorrhoeae, is a major challenge in treating ophthalmia neonatorum.Areas covered: This review explores the epidemiology and diagnosis of ophthalmia neonatorum and analyses the history and practices of prophylaxis and treatment. In this context, the challenges in treating ophthalmia neonatorum today are discussed and innovations that may overcome these challenges in the future are presented. Advantages and challenges of strategies to prevent ophthalmia neonatorum involving prophylaxis of infants and those using screening and treatment of mothers are explored. Expert commentary:Despite the potential to rapidly cause blindness, there are no universal guidelines for the prevention and treatment of ophthalmia neonatorum. Due to the increasing number of treatment failures, particularly those of extensively drug-resistant N. gonorrhoeae, a pragmatic approach is needed. Enhanced availability of screening and treatment of pregnant mothers, coupled with development of new antimicrobial ocular prophylaxis and treatments, provide options for a variety of settings.
Ocular infections caused by bacterial pathogens may damage the cornea and rapidly progress to permanent blindness. Topical application of an ophthalmic formulation is often used to treat corneal infections. The animal models used in many preclinical studies frequently involve expensive in vivo experiments that compromises the corneal epithelium to mimic real life conditions such as during contact lens wear, but these do not consider other instances where infection occurs in intact corneas such as in ophthalmia neonatorum. To develop an ex vivo model of infection, bovine eyes from human food chain waste were processed and the corneas inoculated with Neisseria gonorrhoeae strain NCCP 11945, Staphylococcus aureus strain 6571, and Pseudomonas aeruginosa strain ATCC 15442 for 1 hour, 4 hours, and 6 hours, respectively. Inoculation included intact bovine corneas and those compromised with scalpel, needle, and blot methods. Recovery of N. gonorrhoeae, S. aureus, and P. aeruginosa colonies demonstrated that infection of bovine corneas was achieved with intact and compromised corneas using this model. In addition, corneas inoculated with the bacteria were treated with a suitable antibiotic, demonstrating clearance of the bacterial infections with at least 5 log10 reduction. This model is appropriate for both establishing infection and testing the ability of antimicrobial agents to clear bacterial eye infections. The bovine ex vivo model is reliable, cost-effective, suitable for different bacteria species, and reduces the need for further animal exploitation in laboratory research.
Pseudomonas aeruginosa and Staphylococcus aureus are bacteria pathogens that cause a myriad of infections affecting various sites in the body including the eyes, ears, lungs, skin, heart, bones, and blood amongst others. These bacteria can be disseminated via the blood to other parts of the body away from the primary site of infection and consequences vary from mild to severe with death occurring in certain instances. Both bacterial infections can occur individually, as well as in co-infection resulting in even worse outcomes. P. aeruginosa and S. aureus exhibit multidrug resistance against current antibiotic treatment regimens, which accentuates the challenge in managing the infections caused by these bacteria. To prevent the looming era of untreatable bacterial infections, alternative treatment regimens that are cost effective and accessible are needed. To explore novel treatment options, twenty-five organic compounds comprising fatty acids and their derivatives were screened for antibacterial activity in broth microdilution assay to determine the minimum inhibitory concentration and minimum bactericidal concentration against both P. aeruginosa and S. aureus. Five candidates (N–nonanoic acid, butyric acid, heptanoic acid, palmitoleic acid, and isopropyl myristate) were effective against P. aeruginosa. Seven candidates (N–nonanoic acid, palmitoleic acid, tridecanoic acid, sebaic acid, undecanoic acid, monolaurin, and monocaprin) were effective against S. aureus. Candidates such as N–nonanoic acid and palmitoleic acid were effective against both P. aeruginosa and S. aureus, demonstrating that the same fatty acids show potential to be used against both Gram negative and Gram positive bacterial infections.
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