A Brief History of Antimicrobial Resistance.

Despite mounting attention in recent years, health threats posed by antimicrobial resistance are not new. Antimicrobial resistance has dogged infectious disease treatment processes since the first modern antimicrobials were discovered.

La plata . Y, además, producto sanitario y medicamento / The silver . and, in addition, medical device and medicine

Este discurso de ingreso en la Real Academia Nacional de Farmacia trata de dar una visión de la plata a través de la historia desde su citación en el Génesis pasando por los hallazgos arqueológicos de Asia Menor, Egipto, las monedas griegas o la alquimia hasta la actualidad, destacando su significado desde el punto de vista económico, social y de poder. También se realiza un breve repaso a sus características como elemento físico y químico, así como de su obtención, depósito y valor. Asimismo, se hace un breve repaso de su incorporación a la cultura popular, como adivinanzas, refranes, etc. además de ser utilizado en infinidad de circunstancias como símbolo de riqueza, al respaldar los sistemas monetarios y como moneda cuyo uso alcanza el 70% de su producción. Se detallan las múltiples cualidades de la plata como elemento no medicinal y de sus aplicaciones, pero, fundamentalmente, se aborda finalmente sus propiedades y aplicaciones terapéuticas, su toxicidad y su utilidad en los campos de la dermatología, como agente antimicrobiano, en la odontología, como suplemento alimentario y su reciente aplicación con la incorporación de las manopartículas de plata en el campo de la terapia oncológica, aún muy discutida y en estudio. (AU)

This admission speech at the Royal National Academy of Pharmacy tries to give a vision of silver through history from its citation in Genesis through the archaeological finds of Asia Minor, Egypt, Greek coins or alchemy up to the present , highlighting its significance from the economic, social and power point of view. There is also a brief review of its characteristics as a physical and chemical element, as well as its obtaining, deposit and value. Likewise, a brief review is made of its incorporation into popular culture, such as riddles, proverbs, etc. In addition to being used in countless circumstances as a symbol of wealth, to support monetary systems and as a currency whose use reaches 70% of its production. The multiple qualities of silver as a non-medicinal element and its applications are detailed, but fundamentally, its properties and therapeutic applications, its toxicity and its usefulness in the fields of dermatology, as an antimicrobial agent, in dentistry, are finally addressed. As a food supplement and its recent application with the incorporation of silver nanoparticles in the field of cancer therapy, still highly discussed and under study. (AU)

Fosfomycin: 50 Years of A Great Discovery (1969-2019)

Introduction and Objectives: Fosfomycin has been with us for more than 50 years; however the history of its discovery is largely unknown. The objective of this article is to recover and make known its lost history. Material and Methods: Retrospective review study on the history of the discovery of fosfomycin based on articles and documents located in Medline/PubMed and Google between 1945 and 2020. For the search of articles in PubMed the MeSH keywords fosfomycin OR fosfomycin history, fosfomycin discovery, Streptomyces fradiae, and in Google the free terms; fosfomycin, fosfomycin history, fosfomycin discovery, Streptomyces fradiae were used. All the papers found were reviewed and those containing any historical review of interest to this research were selected for study. Results: We found 3500 articles on fosfomycin, of which 32 (0.9%) dealt with some aspect related to its discovery, and 21 corresponded to its history (0.6%), divided between 13 publications and 7 press releases, 8 to the genus Streptomyces (0.2%) and 3 to fosfomycin (0.1%). Conclusions: The story of the discovery of fosfomycin begins with the finding of the bacterium Streptomyces fradiae in a soil sample from mount Montgó between Dénia and Jávea (Alicante). There is little published literature and the existing one is mostly incomplete. Some medical publications and press releases have made it possible to recover its history (AU)

Introducción y Objectivos: La fosfomicina lleva entre nosotros más de 50 años; sin embargo la historia de sudescubrimiento es una gran desconocida. El objetivo deeste artículo es recuperar y dar a conocer su perdida historia.Material y Metodos: Estudio de revisión retrospectivo sobre la historia del descubrimiento de la fosfomicina basado en artículos y documentos localizados en Medline/PubMed y Google entre 1945 y 2020. Para la búsquedade artículos en PubMed se emplearon las palabras claveen términos MeSH fosfomycin OR fosfomycin history, fosfomycin discovery, Streptomyces fradiae y en Google lostérminos libres; fosfomicina, fosfomicina historia, fosfomicina descubrimiento, Streptomyces fradiae. Se revisaron todos los trabajos encontrados y se seleccionaron paraestudio los que contenían cualquier reseña histórica de interés para esta investigación.Resultados: Se encontraron 3500 artículos sobre fosfomicina, de los cuales 32 (0,9%) trataban algún aspectorelacionado con su descubrimiento y correspondían 21 a suhistoria (0,6%), repartidos entre 13 publicaciones y 8 notasde prensa, 7 al género Streptomyces (0,2%) y 4 a fosfomicina (0,1%).Conclusiones: La historia del descubrimiento de lafosfomicina comienza con el hallazgo de la bacteria Streptomyces fradiae en una muestra de tierra procedente delmonte Montgó entre Dénia y Jávea (Alicante). Existe escasa literatura publicada y la existente es la mayoría de veces incompleta. Algunas publicaciones médicas y notas deprensa han permitido recuperar su historia. (AU)

Emergence of methicillin resistance predates the clinical use of antibiotics.

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two ß-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

Why Do Antibiotics Exist?

In the struggle with antibiotic resistance, we are losing. There is now a serious threat of moving into a postantibiotic world. High levels of resistance, in terms of both frequency and strength, have evolved against all clinically approved antibiotics worldwide. The usable life span of new clinically approved antibiotics is typically less than a decade before resistance reaches frequencies so high as to require only guarded usage. However, microbes have produced antibiotics for millennia without resistance becoming an existential issue. If resistance is the inevitable consequence of antibiotic usage, as has been the human experience, why has it not become an issue for microbes as well, especially since resistance genes are as prevalent in nature as the genes responsible for antibiotic production? Here, we ask how antibiotics can exist given the almost ubiquitous presence of resistance genes in the very microbes that have produced and used antibiotics since before humans walked the planet. We find that the context of both production and usage of antibiotics by microbes may be key to understanding how resistance is managed over time, with antibiotic synthesis and resistance existing in a paired relationship, much like a cipher and key, that impacts microbial community assembly. Finally, we put forward the cohesive, ecologically based "secret society" hypothesis to explain the longevity of antibiotics in nature.

Evolución del consumo de antibióticos a nivel extrahospitalario en Asturias, España (2005-2018) / Evolution of antibiotic consumption in pediatric outpatients of Asturias, Spain (2005-2018)

Introducción: El consumo de antibióticos en España es elevado y más del 90% de las prescripciones se realizan en ámbito extrahospitalario. La exposición a antibióticos en la edad infantil es alta. El objetivo de este estudio es describir la evolución del consumo extrahospitalario de antibióticos en la población pediátrica del Principado de Asturias entre 2005 y 2018.Material y métodos: Estudio descriptivo y retrospectivo del consumo de antibacterianos de uso sistémico (grupo J01 de la clasificación ATC, Anatomical Therapeutic Chemical Classification) en ámbito extrahospitalario en la población pediátrica (0-13 años) del Principado de Asturias entre 2005 y 2018. Se compara el consumo, medido en número de dosis diarias definidas (DDD) por 1.000 habitantes y día (DHD), en 3 periodos de tiempo.Resultados: El consumo medio de antibacterianos en la población pediátrica asturiana (2005-2018) fue de 14 DHD (IC95% 13,4-14,6), con un aumento hasta 2009 (15,2 DHD) y descenso a partir de 2015 (11,9 DHD en 2018). A lo largo del estudio se detectó: 1) un aumento del consumo de amoxicilina (p=0,027), que supera al de amoxicilina-clavulánico desde el año 2011; 2) un consumo estable de macrólidos, con un aumento de azitromicina (p<0,001) y un descenso de claritromicina (p=0,001); 3) un descenso del consumo de cefalosporinas (p<0,001); 4) un aumento del consumo de quinolonas (p=0,002).Conclusiones: El consumo de antibióticos a nivel extrahospitalario en la población pediátrica del Principado de Asturias entre los años 2005 y 2018 ha experimentado un descenso mantenido en los últimos años y una mejora evolutiva del patrón de uso. (AU)

Introduction: Data about consumption of antibiotics in Spain are worrisome. They are mainly prescribed in the community sector and there is a high exposure to antibiotics in the pediatric population. The aim of this study is to describe the evolution of antibiotic consumption in the pediatric population of Asturias during 2005-2018 period.Material and methods: Retrospective and descriptive study using data about consumption of antibacterial agents for systemic use (J01 group of the Anatomical Therapeutic Chemical Classification) in pediatric outpatients in Principado de Asturias between 2005 and 2018. Data, expressed as defined daily dose (DDD) per 1000 inhabitants per day (DID), in three periods were compared.Results: Mean antibiotic consumption in pediatric outpatients in Principado de Asturias (2005-2018) was 14 DID (CI95% 13.4-14.6). Consumption increased until 2009 (15.2 DID) and decreased from 2015 onwards (11.9 DID in 2018). Remarkable data along the study were: 1) increase in amoxicillin consumption (p=0.027), that have exceeded that of amoxicillin-clavulanate since 2011; 2) steady consumption of macrolides, with an increase in azithromycin (p<0.001) and a decrease in clarithromycin (p=0.001); 3) reduction of cephalosporins consumption (p<0.001); 4) increase in quinolones consumption (p=0.002).Conclusions: Global antibiotic consumption in pediatric outpatients in Principado de Asturias between 2005 and 2018 has experienced a constant decrease lately and an improvement in patterns of antibacterial use. (AU)

Possible drugs for the treatment of bacterial infections in the future: anti-virulence drugs.

Antibiotic resistance is a global threat that should be urgently resolved. Finding a new antibiotic is one way, whereas the repression of the dissemination of virulent pathogenic bacteria is another. From this point of view, this paper summarizes first the mechanisms of conjugation and transformation, two important processes of horizontal gene transfer, and then discusses the approaches for disarming virulent pathogenic bacteria, that is, virulence factor inhibitors. In contrast to antibiotics, anti-virulence drugs do not impose a high selective pressure on a bacterial population, and repress the dissemination of antibiotic resistance and virulence genes. Disarmed virulence factors make virulent pathogens avirulent bacteria or pathobionts, so that we human will be able to coexist with these disarmed bacteria peacefully.

Antimicrobial resistance: more than 70 years of war between humans and bacteria.

Development of antibiotic resistance in bacteria is one of the major issues in the present world and one of the greatest threats faced by mankind. Resistance is spread through both vertical gene transfer (parent to offspring) as well as by horizontal gene transfer like transformation, transduction and conjugation. The main mechanisms of resistance are limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. The highest quantities of antibiotic concentrations are usually found in areas with strong anthropogenic pressures, for example medical source (e.g., hospitals) effluents, pharmaceutical industries, wastewater influents, soils treated with manure, animal husbandry and aquaculture (where antibiotics are generally used as in-feed preparations). Hence, the strong selective pressure applied by antimicrobial use has forced microorganisms to evolve for survival. The guts of animals and humans, wastewater treatment plants, hospital and community effluents, animal husbandry and aquaculture runoffs have been designated as "hotspots for AMR genes" because the high density of bacteria, phages, and plasmids in these settings allows significant genetic exchange and recombination. Evidence from the literature suggests that the knowledge of antibiotic resistance in the population is still scarce. Tackling antimicrobial resistance requires a wide range of strategies, for example, more research in antibiotic production, the need of educating patients and the general public, as well as developing alternatives to antibiotics (briefly discussed in the conclusions of this article).

[An allied miracle cure; how liberators introduced penicillin in the Netherlands]. / Een geallieerd wondermiddel.

The introduction of penicillin to medical practice in the Netherlands is closely related to the liberation of the Netherlands from Nazi occupation. The allied forces brought penicillin - of which they had vast quantities - to the Netherlands and introduced it to Dutch doctors. In many of the oldest documented cases involving the use of penicillin in the Netherlands, allied army doctors gave the ampoules of penicillin to Dutch doctors, who used the until then unknown medicine as a last-resort drug to treat patients with severe infections that had failed to respond to other treatments. The archives of the Dutch Journal of Medicine (NTvG) contain numerous interesting examples of case reports. A public call on the website of the Dutch public news broadcaster NOS resulted in several other apt examples. It is, however, not known exactly who the first Dutch patient to receive penicillin was.

The History of Wound Healing.

Since the dawn of humanity, wounds have afflicted humans, and healers have held responsibility for treating them. This article tracks the evolution of wound care from antiquity to the present, highlighting the roles of surgeons, scientists, culture, and society in the ever-changing management of traumatic and iatrogenic injuries.

The interweaving roles of mineral and microbiome in shaping the antibacterial activity of archaeological medicinal clays.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal Earths (MEs), natural aluminosilicate-based substances (largely kaolinite and montmorillonite), have been part of the European pharmacopoeia for well over two millennia; they were used generically as antidotes to 'poison'. AIM OF THE STUDY: To test the antibacterial activity of three Lemnian and three Silesian Earths, medicinal earths in the collection of the Pharmacy Museum of the University of Basel, dating to 16th-18th century and following the methodology outlined in the graphical abstract. To compare them with natural clays of the same composition (reference clays) and synthetic clays (natural clays spiked with elements such as B, Al, Ti and Fe); to assess the parameters which drive antibacterial activity, when present, in each group of samples. MATERIALS AND METHODS: a total of 31 samples are investigated chemically (ICP-MS), mineralogically (both bulk (XRD) and at the nano-sized level (TEM-EDAX)); their organic load (bacterial and fungal) is DNA-sequenced; their bioactivity (MIC60) is tested against Gram-positive, S. aureus and Gram-negative, P. aeruginosa. RESULTS: Reference smectites and kaolinites show no antibacterial activity against the above pathogens. However, the same clays when spiked with B or Al (but not with Ti or Fe) do show antibacterial activity. Of the six MEs, only two are antibacterial against both pathogens. Following DNA sequencing of the bioactive MEs, we show the presence within of a fungal component, Talaromyces sp, a fungus of the family of Trichocomaceae (order Eurotiales), historically associated with Penicillium. Talaromyces is a known producer of the exometabolite bioxanthracene B, and in an earlier publication we have already identified a closely related member of the bioxanthracene group, in association with one of the LE samples examined here. By linking fungus to its exometabolite we suggest that this fungal load may be the key parameter driving antibacterial activity of the MEs. CONCLUSIONS: Antibacterial activity in kaolinite and smectite clays can arise either from spiking natural clays with elements like B and Al, or from an organic (fungal) load found only within some archaeological earths. It cannot be assumed, a priori, that this organic load was acquired randomly and as a result of long-term storage in museum collections. This is because, at least in the case of medicinal Lemnian Earth, there is historical evidence to suggest that the addition of a fungal component may have been deliberate.

Breve historia del cloranfenicol en oftalmología. ¿Es seguro su uso? / Brief history of chloramphenicol in ophthalmology. Is it safe to use?

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