The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use
01 May 2017-Emerging Infectious Diseases (Centers for Disease Control and Prevention)-Vol. 23, Iss: 5, pp 849-853
TL;DR: The unusual serendipity involved in the discovery of penicillin demonstrates the difficulties in finding new antibiotics and should remind health professionals to expertly manage these extraordinary medicines.
Abstract: After just over 75 years of penicillin’s clinical use, the world can see that its impact was immediate and profound. In 1928, a chance event in Alexander Fleming’s London laboratory changed the course of medicine. However, the purification and first clinical use of penicillin would take more than a decade. Unprecedented United States/Great Britain cooperation to produce penicillin was incredibly successful by 1943. This success overshadowed efforts to produce penicillin during World War II in Europe, particularly in the Netherlands. Information about these efforts, available only in the last 10–15 years, provides new insights into the story of the first antibiotic. Researchers in the Netherlands produced penicillin using their own production methods and marketed it in 1946, which eventually increased the penicillin supply and decreased the price. The unusual serendipity involved in the discovery of penicillin demonstrates the difficulties in finding new antibiotics and should remind health professionals to expertly manage these extraordinary medicines.
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TL;DR: Focusing on product development and technological improvements will enable acoustofluidic separation to find real-world applications, the researchers conclude.
Abstract: Acoustofluidics, the integration of acoustics and microfluidics, is a rapidly growing research field that is addressing challenges in biology, medicine, chemistry, engineering, and physics. In particular, acoustofluidic separation of biological targets from complex fluids has proven to be a powerful tool due to the label-free, biocompatible, and contact-free nature of the technology. By carefully designing and tuning the applied acoustic field, cells and other bioparticles can be isolated with high yield, purity, and biocompatibility. Recent advances in acoustofluidics, such as the development of automated, point-of-care devices for isolating sub-micron bioparticles, address many of the limitations of conventional separation tools. More importantly, advances in the research lab are quickly being adopted to solve clinical problems. In this review article, we discuss working principles of acoustofluidic separation, compare different approaches of acoustofluidic separation, and provide a synopsis of how it is being applied in both traditional applications, such as blood component separation, cell washing, and fluorescence activated cell sorting, as well as emerging applications, including circulating tumor cell and exosome isolation.
240 citations
TL;DR: The aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug.
Abstract: The emergence and spread of antibiotic-resistant pathogens is a major public health issue, which requires global action of an intersectoral nature. Multidrug-resistant (MDR) pathogens—especially “ESKAPE” bacteria—can withstand lethal doses of antibiotics with various chemical structures and mechanisms of action. Pharmaceutical companies are increasingly turning away from participating in the development of new antibiotics, due to the regulatory environment and the financial risks. There is an urgent need for innovation in antibiotic research, as classical discovery platforms (e.g., mining soil Streptomycetes) are no longer viable options. In addition to discovery platforms, a concept of an ideal antibiotic should be postulated, to act as a blueprint for future drugs, and to aid researchers, pharmaceutical companies, and relevant stakeholders in selecting lead compounds. Based on 150 references, the aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug (a prodrug or generally reactive compound with no specific target, broad-spectrum antibacterial activity, adequate penetration through the Gram-negative cell wall, activity in biofilms and in hard-to-treat infections, accumulation in macrophages, availability for oral administration, and for use in sensitive patient groups).
214 citations
Cites background from "The Discovery of Penicillin—New Ins..."
...The discovery and clinical use of antibiotics may be considered to be one the greatest achievements in the history of medicine [1]....
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TL;DR: The aim of this review is to recap the history, the emergence, and clinical features of various MRSA infections, and to summarize the current advances regarding MRSA screening, typing, and therapeutic options for an audience of clinical microbiologists and infectious disease specialists.
Abstract: Staphylococcus aureus has been an exceptionally successful pathogen, which is still relevant in modern age-medicine due to its adaptability and tenacity. This bacterium may be a causative agent in a plethora of infections, owing to its abundance (in the environment and in the normal flora) and the variety of virulence factors that it possesses. Methicillin-resistant S. aureus (MRSA) strains-first described in 1961-are characterized by an altered penicillin-binding protein (PBP2a/c) and resistance to all penicillins, cephalosporins, and carbapenems, which makes the β-lactam armamentarium clinically ineffective. The acquisition of additional resistance determinants further complicates their eradication; therefore, MRSA can be considered as the first representative of multidrug-resistant bacteria. Based on 230 references, the aim of this review is to recap the history, the emergence, and clinical features of various MRSA infections (hospital-, community-, and livestock-associated), and to summarize the current advances regarding MRSA screening, typing, and therapeutic options (including lipoglycopeptides, oxazolidinones, anti-MRSA cephalosporins, novel pleuromutilin-, tetracycline- and quinolone-derivatives, daptomycin, fusidic acid, in addition to drug candidates in the development phase), both for an audience of clinical microbiologists and infectious disease specialists.
180 citations
Cites background from "The Discovery of Penicillin—New Ins..."
...These infections became successfully treatable after the paradigm-altering discovery of penicillin by Alexander Fleming, due to the uniform susceptibility of these bacteria [26]....
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TL;DR: Suggestions on how to address this public health threat are suggested, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR are concluded.
Abstract: Antibiotics changed medical practice by significantly decreasing the morbidity and mortality associated with bacterial infection. However, infectious diseases remain the leading cause of death in the world. There is global concern about the rise in antimicrobial resistance (AMR), which affects both developed and developing countries. AMR is a public health challenge with extensive health, economic, and societal implications. This paper sets AMR in context, starting with the history of antibiotics, including the discovery of penicillin and the golden era of antibiotics, before exploring the problems and challenges we now face due to AMR. Among the factors discussed is the low level of development of new antimicrobials and the irrational prescribing of antibiotics in developed and developing countries. A fundamental problem is the knowledge, attitude, and practice (KAP) regarding antibiotics among medical practitioners, and we explore this aspect in some depth, including a discussion on the KAP among medical students. We conclude with suggestions on how to address this public health threat, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR.
113 citations
Cites background from "The Discovery of Penicillin—New Ins..."
...In 1945, Sir Alexander Fleming, with Sir Howard Florey and Ernst Chain, were awarded the Nobel Prize in Physiology/Medicine for the invention of penicillin to treat several infectious diseases (45, 48)....
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...Ernst Chain and Howard Florey then isolated the pure form of penicillin in the form of penicillin G, and production was scaled up, making the antibiotic available for increasingly widespread clinical use from 1942, initially for allied force military community, but was extensively marketed for civilians after the Second World War (1, 48)....
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University of Dhaka1, Loyola University Chicago2, BGC Trust University Bangladesh3, Indian Veterinary Research Institute4, Mawlana Bhashani Science and Technology University5, University of Szeged6, Sarhad University of Science & IT, Ring Road (Hayatabad Link) Peshawar7, State University of Bangladesh8, Kathmandu9
TL;DR: Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications.
99 citations
References
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Journal Article•
TL;DR: It is suggested that it may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes, and its value as an aid to the isolation of B. influenzae has been demonstrated.
Abstract: 1. A certain type of penicillium produces in culture a powerful antibacterial substance. The antibacterial power of the culture reaches its maximum in about 7 days at 20o C. and after 10 days diminishes until it has almost disappeared in 4 weeks. 2. The best medium found for the production of the antibacterial substance has been ordinary nutrient broth. 3. The active agent is readily filterable and the name "penicillin" has been given to filtrates of broth cultures of the mould. 4. Penicillin loses most of its power after 10 to 14 days at room temperature but can be preserved longer by neutralization. 5. The active agent is not destroyed by boiling for a few minutes but in alkaline solution boiling for 1 hour markedly reduces the power. Autoclaving for 20 minutes at 115o C. practically destroys it. It is soluble in alcohol but insoluble in ether or chloroform. 6. The action is very marked on the pyogenic cocci and the diphtheria group of bacilli. Many bacteria are quite insensitive, e.g. the coli-typhoid group, the influenza-bacillus group, and the enterococcus. 7. Penicillin is non-toxic to animals in enormous doses and is non-irritant. It doses not interfere with leucocytic function to a greater degree than does ordinary broth. 8. It is suggested that it may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes. 9. The use of penicillin on culture plates renders obvious many bacterial inhibitions which are not very evident in ordinary cultures. 10. Its value as an aid to the isolation of B. influenzae has been demonstrated.
1,503 citations
695 citations
"The Discovery of Penicillin—New Ins..." refers background in this paper
...The Oxford team then published their clinical findings (5)....
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TL;DR: This survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive.
Abstract: Infections caused by antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's “10 × '20 Initiative.”
649 citations
TL;DR: In 1929, while examining plates seeded with staphylococci, Fleming observed that colonies failed to grow in the neighborhood of a colony of a contaminating mold.
Abstract: Excerpt In 1929, while examining plates seeded with staphylococci, Fleming1observed that colonies failed to grow in the neighborhood of a colony of a contaminating mold. Following up this chance ob...
134 citations
"The Discovery of Penicillin—New Ins..." refers background in this paper
...” The researchers published their findings in The Lancet in August 1940, describing the production, purification, and experimental use of penicillin that had sufficient potency to protect animals infected with Streptococcus pyogenes, Staphylococcus aureus, and Clostridium septique (4)....
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