Computer-aided drug repurposing to tackle antibiotic resistance based on topological data analysis.

The progressive emergence of antimicrobial resistance has become a global health problem in need of rapid solution. Research into new antimicrobial drugs is imperative. Drug repositioning, together with computational mathematical prediction models, could be a fast and efficient method of searching for new antibiotics. The aim of this study was to identify compounds with potential antimicrobial capacity against Escherichia coli from US Food and Drug Administration-approved drugs, and the similarity between known drug targets and E. coli proteins using a topological structure-activity data analysis model. This model has been shown to identify molecules with known antibiotic capacity, such as carbapenems and cephalosporins, as well as new molecules that could act as antimicrobials. Topological similarities were also found between E. coli proteins and proteins from different bacterial species such as Mycobacterium tuberculosis, Pseudomonas aeruginosa and Salmonella Typhimurium, which could imply that the selected molecules have a broader spectrum than expected. These molecules include antitumor drugs, antihistamines, lipid-lowering agents, hypoglycemic agents, antidepressants, nucleotides, and nucleosides, among others. The results presented in this study prove the ability of computational mathematical prediction models to predict molecules with potential antimicrobial capacity and/or possible new pharmacological targets of interest in the design of new antibiotics and in the better understanding of antimicrobial resistance.

Innovative gamification and outreach tools to raise awareness about antimicrobial resistance.

Since 2017, the SWICEU team has developed various informative actions and innovative gamification supports to educate and raise awareness about antimicrobial resistance (AMR) and the correct use of antibiotics among the general population especially among young people. This case study presents the results obtained in the last 5 years with the strategies carried out by this team, composed of students and professors of Health Sciences, Industrial Design Engineering, and Communication Sciences at CEU Cardenal Herrera University (CEU UCH) in Valencia (Spain). Over the past 5 years, playful educational supports have been developed to make the health problem of bacterial resistance and the action of antibiotics more understandable among young people. The dissemination media used, with the same objective of teaching and raising awareness about AMR in a creative and innovative way, have been selected according to the trends in digital communication and use of scientific and health content provided by the most recent studies carried out among the Spanish population. These strategies have included decalogues or "tips" with useful advice, infographics, YouTube videos, Twitter threads, online challenges on Kahoot, stories on Instagram, use of QR codes, etc. These actions have also obtained diffusion in the media and have been awarded by different national and international entities. The good results obtained in the case under study allow us to establish recommendations for the design of innovative educational gamification and dissemination supports on AMR, especially aimed at younger audiences.

Severe Acute Hepatitis of Unknown Origin in Children: What Do We Know Today?

In May 2022, the UK International Health Regulations National Focal Point notified World Health Organization of 176 cases of severe acute hepatitis of unknown etiology in children under 10 years of age. From that moment on, cases of severe acute hepatitis of unknown origin in children began to be reported in several countries. As of June 17, 2022, a total of 991 cases had been reported in 35 countries worldwide, 50 children needed a liver transplant and 28 patients died. According to information published by ECDC, 449 cases have been detected in 21 EU countries. The children were between 1 month and 16 years of age. Adenovirus was detected in 62.2% of the analyzed samples. So far, the cause of these cases is unknown and many hypotheses remain open, but hepatitis A-E viruses and COVID-19 vaccines have been ruled out. A possible hypothesis has been published to explain the cause of these cases of severe hepatitis, according to which it could be a consequence of adenovirus infection in the intestine in healthy children previously infected with SARS-CoV-2. No other clear epidemiological risk factors have been identified to date. Thus, at this time, the etiology of the current cases of hepatitis remains under active investigation.

Evaluation of knowledge about antibiotics and engagement with a research experience on antimicrobial resistance between pre-university and university students for five school years (2017-2021).

Antimicrobial resistance (AMR) remains a serious global health problem. Spain is the fifth country in Europe with the highest consumption of antibiotics, due in part to ignorance of the good use of these drugs and the problem of AMR. To avoid a post-antibiotic era, adequate training on this problem is key to create social awareness. This study aimed to evaluate the impact that the SWICEU project, an academic program about antibiotic discovery, has had on the knowledge of AMR and rational use of antimicrobials in pre-university students from seven schools in the province of Valencia during five academic years (2017-2021), as well as to evaluate the level of satisfaction of university and pre-university students who have participated in the project. For this study, a survey was carried out with multiple-choice questions with a single correct answer to evaluate the knowledge acquired by pre-university students before and after the project. A satisfaction survey was also designed with a Likert scale from the lowest to the highest level of satisfaction for the two groups of students after the project. Data on knowledge surveys indicated an increase in the mean number of correct answers after the sessions. In satisfaction surveys, we highlighted the issue that referred to the project's recommendation. The data obtained confirm this project as a valuable activity, as it allows learning about AMR and the rational use of antibiotics in a pleasing and attractive way for young pre-university and university students.

Antibiotic resistant bacteria: current situation and treatment options to accelerate the development of a new antimicrobial arsenal.

INTRODUCTION: Antibiotic resistance is one of the biggest public health threats worldwide. Currently, antibiotic-resistant bacteria kill 700,000 people every year. These data represent the near future in which we find ourselves, a 'post-antibiotic era' where the identification and development of new treatments are key. This review is focused on the current and emerging antimicrobial therapies which can solve this global threat. AREAS COVERED: Through a literature search using databases such as Medline and Web of Science, and search engines such as Google Scholar, different antimicrobial therapies were analyzed, including pathogen-oriented therapy, phagotherapy, microbiota and antivirulent therapy. Additionally, the development pathways of new antibiotics were described, emphasizing on the potential advantages that the combination of a drug repurposing strategy with the application of mathematical prediction models could bring to solve the problem of AMRs. EXPERT OPINION: This review offers several starting points to solve a single problem: reducing the number of AMR. The data suggest that the strategies described could provide many benefits to improve antimicrobial treatments. However, the development of new antimicrobials remains necessary. Drug repurposing, with the application of mathematical prediction models, is considered to be of interest due to its rapid and effective potential to increase the current therapeutic arsenal.

Antibiotic resistance is currently one of the biggest public health threats worldwide. Right now, antibiotic-resistant bacteria kill 700,000 people every year. Many of the available antibiotics are useless against drug resistant bacteria. The present and near future in which we find ourselves is a post-antibiotic era, where the antibiotics we have are unable to combat the bacterial infections that are emerging. In this review, published studies were accessed to explore different techniques that are available to improve existing treatment options. Currently, these strategies cannot replace antibiotic therapy. The reviewed knowledge presents these alternatives as adjuvants to antibiotic treatments. Therefore, research into new antibiotics remains important. This review exposes that the repurposing of known drugs as antibiotics could contribute to the cost-effective search of new antibiotics in a faster and cost-effective way compared to traditional development methods of new antibiotics. The review emphasizes the urgency of identifying new pharmacological targets that can aid in the development of new therapies, and to improve known alternative therapies. Drug repurposing can greatly shorten the time and cost of development of new antibiotics. This strategy adds to the value of certain commercialized molecules, recovering part of the investment made by the pharmaceutic industry. In addition, it provides greater knowledge about other alternative antibiotic therapies and about the mechanisms by which bacteria develop antibiotic resistance.