Alexander Fleming: a second look.

In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming's laboratory in its original location at St. Mary's Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.

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.

Terapia antibacteriana: origen y evolución en el tiempo / Antibacterial therapy: origin and evolution in the time

Desde siempre, el ser humano buscó una explicación a los fenómenos y una solución a sus males. El instinto fue quien primero guió al hombre para buscar remedios con los que aliviar sus males lamiendo o limpiando sus heridas. Mediante el método de "ensayo-error", el hombre prehistórico fue encontrando plantas y sustancias minerales que resultaban eficaces. En la Edad Media y el Mundo Moderno, la medicina Hippocrático-galénica tuvo, en relación a la terapéutica, a Dioscórides como el gran referente Con el decurso de los años, científicos como Pasteur, Koch, Cantani, Emmerich, Low, Tiberio, sentaron las bases para que más tarde otros como Freudenreich, Domagk, Fleming, Waksman, entre otros, descubrieran y perfeccionaran la amplia gama de antibióticos que hoy conocemos. A pesar de estos avances, en la actualidad se observan múltiples mecanismos de resistencia bacteriana que ponen en peligro la eficacia antibiótica (AU).

The human beings have always looked for an explanation to the phenomena and a solution to his misfortunes. Firstly the instinct was what guided the man to look for remedies to alleviate his ills licking or cleaning his wounds. By means of the "trial-error" method, the prehistoric man was finding plants and mineral substances that were effective. In the Middle Ages and the Modern World, the Hippocratic-galenic medicine took Dioscorides as the great referent in relation to therapeutic. As the years went by, scientist like Pasteur, Koch, Cantani, Emmerich, Low, Tiberio, set the bases for Freudenreich, Domagk, Fleming, Waksman among others to discover and improve the wide range antibiotics known today. In spite of these advances, multiple mechanisms of bacterial resistance putting in danger antibiotic effectiveness are observed today (AU).

Relato de 3 Casos de Complicações de Otite Média Aguda / Report of 3 Cases of Complications of Acute Otitis Media

Antes da introdução dos antibióticos na prática clínica, a disseminação do processo infeccioso da orelha média para as estruturas adjacentes frequentemente resultava em complicações graves, que atualmente são mais comuns nos países em desenvolvimento, como o Brasil, do que nos países desenvolvidos, e mais prevalentes nas primeiras duas décadas de vida. Este trabalho relata três casos clínicos de complicações de otite média aguda atendidos no Hospital Universitário São Francisco de Assis no ano de 2015, através das revisões dos prontuários, que foram analisados e discutidos com base na literatura atual. As complicações de otites médias agudas podem ser graves e potencialmente fatais. (AU)

Prior to the introduction of antibiotics into clinical practice, dissemination of the infectious process from the middle ear to adjacent structures often resulted in severe complications, which are currently more common in developing countries, such as Brazil, than in developed countries, and more prevalent in the first two decades of life. This paper reports three clinical cases of acute otitis media complications treated at the São Francisco de Assis University Hospital in 2015, through medical records reviews, which were analyzed and discussed based on current literature. The complications of acute otitis media can be serious and potentially fatal. (AU)

[Chemotherapy: from bacteria killer to antitumor agent : A striking transformation in the term over the last century]. / Chemotherapie: vom Bakterienkiller zum Tumortherapeutikum : Ein entscheidender Begriffswandel in den letzten hundert Jahren.

The term chemotherapy is more than 100 years old and during this period it has been going through decisive changes in terminology. Initially describing an antibacterial therapy it now is known as a part of the new oncologic therapy. Those upheavels and their causes are represented. Conclusively, the evolution of the urooncologic chemotherapy is briefly outlined.

Penicillin: promise, problems and practice in wartime Edinburgh.

While medical historians have paid ample attention to the introduction of antibiotics and their impact on hospital-based practice during and after the Second World War, the multiple issues surrounding their use in Scottish hospitalsare sorely lacking in current discussions. Drawing on an extensive yet underused range of materials including patient treatment records, oral histories and medical correspondence, this paper explores the introduction of penicillin for civilian treatment at the Royal Infirmary of Edinburgh during the closing stages of the War. It highlights the success of the drug in clinical treatment as well as its shortcomings, offering an alternative view of its initial impact on surgical practice.

A history of the treatment of appendicitis in children: lessons learned.

During the latter half of the 19th century, surgeons increasingly reported performing appendicectomies. Fitz from Harvard, Groves from Canada and Tait from Britain all recorded successful removal of the appendix. McBurney described the point of maximal tenderness in classic appendicitis and also the muscle-splitting incision centred on this point. Priority is given to McArthur in describing the lateral muscle-splitting incision. The direction of the cutaneous incision was later modified by Elliott and Lanz. Incisions that healed well were essential to recovery. Appendicectomy became a 'fashionable' operation after the London surgeon, Treves, removed the appendix of King Edward VII. Through the 20th century, the mortality from appendicitis fell notably with the advent of sulphonamide and penicillin, improvements in fluid therapy and safer anaesthesia. By 1990, diagnostic delay was the main cause of death. Semm performed the first laparoscopic appendicectomy in 1990, roundly criticized at the time for what is now a routine procedure. We view contemporary debates on the indications for appendicectomy, the best approach and how to optimize recovery in the light of the history of this intriguing disease.

Past, present and future of macrolide therapy for chronic rhinosinusitis in Japan.

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Cooperative development of antimicrobials: looking back to look ahead.

As foundations and governments mobilize to tackle antimicrobial resistance (AMR), several experiments in academic-industrial collaboration have emerged. Here, I examine two historical precedents, the Penicillin Project and the Malaria Project of the Second World War, and two contemporary examples, the Tuberculosis Drug Accelerator programme and the Tres Cantos Open Lab. These and related experiments suggest that different strategies can be effective in managing academic-industrial collaborations, and that such joint projects can prosper in both multisite and single-site forms, depending on the specific challenges and goals of each project. The success of these strategies and the crisis of AMR warrant additional investment in similar projects.

Antagonismo microbiano en la terapia de las enfermedades infecciosas / Microbial antagonism in the therapy of infectious diseases

The history of antibiotics begins with the first observations of Pasteur and Joubert about microbial antagonism at the end of the XIX century. Three types of antagonism were studied: bacterial killing by other bacteria, virus against bacteria and blockade of cellular receptors by bacterial filtrates. In the first type, the piocianase from Pseudomonas aeruginosaand the activity of Bacillus subtilisover Mycobacterium tuberculosiswere the better examples; in the second, the French D'Herelle was a pioneer using bacteriophages against Shigella dysenteriae;and another French, Besredka, headed the third line with his "antivirus thérapie" on Staphylococcus aureus.

La historia de los antibióticos comienza con las primeras observaciones de Pasteur y Joubert sobre el antagonismo entre bacterias, realizadas a fines del siglo XIX. Tres tipos de antagonismo fueron objeto de estudio: bacterias que mataban a otras bacterias, virus capaces de lisar bacterias y bloqueo de receptores celulares del huésped por filtrados bacterianos. En el primer tipo de antagonismo, los mejores ejemplos fueron la actividad de la piocianasa producida por Pseudomonas aeruginosay la acción de Bacillus subtilissobre Mycobacterium tuberculosis;en el segundo descuella el francés D'Herelle como pionero al emplear bacteriófagos contra Shigella dysenteriae,en tanto que el ucraniano-francés Besredka encabeza el tercer tipo con su "antivirusthérapie "en Syaphylococcus aureus.Con el tiempo, la primera línea triunfaría, con una ligera modificación, al enfrentar hongos contra bacterias.

History of antibiotics: from fluoroquinolones to daptomycin (Part 2).

In the Modern Era, physicians attested to the reciprocal influence among a technologically advanced society, rapid scientific progresses in medicine, and the need for new antimicrobials. The results of these changes were not only seen in the prolongation of life expectancy but also by the emergence of new pathogens. We first observed the advent of Gram-negative bacteria as a major source of nosocomial infections. The treatment of these microorganisms was complicated by the appearance and spread of drug resistance. We first focused on the development of two major classes of antimicrobials still currently used for the treatment of Gram-negative bacteria, such as fluoroquinolones and carbapenemes. Subsequently, we directed our attention to the growth of the incidence of infections due to Methicillin-Resistant Staphylococcus aureus (MRSA). Although the first MRSA was already isolated in 1961, the treatment of this new pathogen has been based on the efficacy of vancomycin for more than four decades. Only in the last 15 yr, we assisted in the development of new antimicrobial agents such as linezolid and daptomycin.

Necessidade de novos antibióticos: [Carta ao Leitor] / The need of new antibiotics: [Letters to the Editor]

Os antibióticos são uma classe de fármacos indispensável; sem eles haveria perdas na expectativa de vida que conquistamos ao longo de décadas. Mas a potência dos antibióticos está ameaçada pela resistência bacteriana. Há uma explosão de casos reportados na literatura. De fato, o aumento da resistência bacteriana, principalmente entre patógenos potencialmente perigosos, tem levado ao aumento na necessidade de novos fármacos e novas classes de antibióticos, tanto para infecções adquiridas em hospitais quanto na comunidade. Entretanto, a despeito dessa necessidade, somente duas novas classes de antibióticos foram introduzidas na medicina desde 1963, quando o ácido nalidíxico foi aprovado: uma em 2000 e uma em 2003. O artigo discute um pouco esta questão.

Antibiotics are a important class of drugs, without them there would be losses in life expectancy achieved over decades. But the power of antibiotics is threatened by bacterial resistance. There is an explosion of cases reported in the literature. In fact, the increase in bacterial resistance, particularly among potentially dangerous pathogens, has led to an increased need for new drugs and new classes of antibiotics for both infections acquired in hospitals and in the community. However, despite this need, only two new classes of antibiotics have been introduced in medicine since 1963, when nalidixic acid was approved: one in 2000 and one in 2003. The article discusses this issue.

How an aspirin, a throat swab from a chicken, and four Guinea pigs changed thoracic surgery.

The development of antituberculous drugs changed thoracic surgery and also markedly lowered the morbidity and mortality of a disease that had epidemic proportions. This article summarizes aspects from 3 important articles that led to the discovery of these drugs.

History of antibiotics. From salvarsan to cephalosporins.

Infections have represented for a long time the leading cause of death in humans. During the 19th century, pneumonia, tuberculosis, diarrhea and diphtheria were considered the main causes of death in children and adults. Only in the late 19th century did it become possible to correlate the existence of microscopic pathogens with the development of various diseases. Within a few years the introduction of antiseptic procedures had begun to reduce mortality due to postsurgical infections. Sanitation and hygiene played a significant role in the reduction of the mortality due to several infectious diseases. The introduction of the first compounds with antimicrobial activity succeeded in conquering many diseases. In this review we analyzed, from a historical perspective, the development of antibiotics and the circumstances that led to their discovery. The first compound with antimicrobial activity was introduced in 1911 by Erlich. He focused his research activity on the discovery of a "magic bullet" to treat syphilis. Afterwards, Foley and colleagues brought penicillin to the forefront. Streptomycin represents the first drug discovered for the treatment of tuberculosis, and its development included the first use of clinical trials. Finally, with the development of cephalosporins, the introduction of new antimicrobial compounds with broad activity against gram-positive and also some gram-negative bacteria began.

The oxazolidinones: past, present, and future.

The success of linezolid stimulated significant efforts to discover new agents in the oxazolidinone class. Over a dozen oxazolidinones have reached the clinic, but many were discontinued due to lack of differentiated potency, inadequate pharmacokinetics, and safety risks that included myelosuppression. Four oxazolidinones are currently undergoing clinical evaluation. The Trius Therapeutics compound tedizolid phosphate (formerly known as torezolid phosphate, TR-701, DA-7218), the most advanced, is in phase 3 clinical trials for acute bacterial skin and skin structure infections. Rib-X completed two phase 2 studies for radezolid (Rx-01_667, RX-1741) in uncomplicated skin and skin structure infections and community-acquired pneumonia. Pfizer and AstraZeneca have each identified antitubercular compounds that have completed phase 1 studies: sutezolid (PNU-100480, PF-02341272) and AZD5847 (AZD2563), respectively. The oxazolidinones share a relatively low frequency of resistance largely due to the requirement of mutations in 23S ribosomal RNA genes. However, maintaining potency against strains carrying the mobile cfr gene poses a challenge for the oxazolidinone class, as well as other 50S ribosome inhibitors that target the peptidyl transferase center.

Penicillin: the medicine with the greatest impact on therapeutic outcomes.

The principal point of this paper is that the discovery of penicillin and the development of the supporting technologies in microbiology and chemical engineering leading to its commercial scale production represent it as the medicine with the greatest impact on therapeutic outcomes. Our nomination of penicillin for the top therapeutic molecule rests on two lines of evidence concerning the impact of this event: (1) the magnitude of the therapeutic outcomes resulting from the clinical application of penicillin and the subsequent widespread use of antibiotics and (2) the technologies developed for production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today. These same technologies became the model for the development and production of new types of bioproducts (i.e., anticancer agents, monoclonal antibodies, and industrial enzymes). The clinical impact of penicillin was large and immediate. By ushering in the widespread clinical use of antibiotics, penicillin was responsible for enabling the control of many infectious diseases that had previously burdened mankind, with subsequent impact on global population demographics. Moreover, the large cumulative public effect of the many new antibiotics and new bioproducts that were developed and commercialized on the basis of the science and technology after penicillin demonstrates that penicillin had the greatest therapeutic impact event of all times.