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It is important for people to understand that if they are feeling under the weather and see their GP or a nurse, antibiotics may not be prescribed if they are not effective for their condition, but they should expect to have a full discussion about how to manage their symptoms. Professor Dame Sally Davies, Chief Medical Officer, comments: Without effective antibiotics, minor infections could become deadly and many medical advances could be at risk; surgery, chemotherapy and caesareans could become simply too dangerous. But reducing inappropriate use of antibiotics can help us stay ahead of superbugs. The public has a critical role to play and can help by taking collective action. I welcome the launch of the ‘Keep Antibiotics Working’ campaign, and remember that antibiotics are not always needed so always take your doctor’s advice. Health Minister Steve Brine said: Following on from the global Call to Action conference held this month, we are asking people to help so we can make sure antibiotics keep working. This government is firmly committed to combatting drug resistant infections and refuses to allow modern medicine to grind to a halt – simple steps can make a huge difference. Dr Chris Van Tulleken, TV and of infectious diseases doctor at University College London Hospitals, comments: As an infectious diseases doctor, I see first-hand what happens if antibiotics don’t work – and it’s scary. Antibiotics are not just vital for treating serious bacterial infections, they’re needed to help with other treatments like chemotherapy. Antibiotic resistance is a problem that will affect every one of us, so we all have a role to play. As GPs we are often asked to prescribe antibiotics by patients who think that they will cure all their ills. The reality is that antibiotics are not always needed so you shouldn’t expect to be prescribed them by your doctor or nurse. Always take their advice and remember that your pharmacist can recommend medicines to help with your symptoms or pain. Public Health England’s new campaign is part of a wider cross-government strategy, involving the agricultural, pharmaceutical and healthcare sectors, which tackles the threat of antibiotic resistance by increasing supply and reducing inappropriate demand. To help keep this precious resource in the fight against infections working, the public are asked to play their part and urged to always take their doctor, nurse or pharmacist’s advice on antibiotics. For further information on antibiotics, their uses and the risk of resistance, search ‘NHS Antibiotics’ online. The campaign will run from Monday 23 October across England for 8 weeks and will be supported with advertising, partnerships with local pharmacies and GP surgeries, and social media. Additional data from Public Health England’s ESPAUR report illustrates: * four in 10 patients with an E.coli bloodstream infection in England cannot be treated with the commonest antibiotic (co-amoxiclav) used in hospitals; in addition, almost 1 in 5 of these bacteria were resistant to at least 1 of 5 other key antibiotics * of the 1 million antibiotic resistant bacteria causing urinary tract infections identified in NHS laboratories in 2016, trimethoprim resistance was very common (37%) but the current recommended first line treatment, nitrofurantoin, remains effective (3%) * between 2012 and 2016, antibiotic prescribing reduced by 5%, when measured as defined daily doses per 1000 inhabitants per day * the number of antibiotic prescriptions dispensed in General Practice decreased by 13% between 2012 and 2016 (-2% from 2015 to 2016) * dental practices dispensed 1 in 5 fewer prescriptions in 2016 compared to 2012 and more than 99% of prescribed antibiotics were in accordance with dental treatment guidelines * hospital prescribing has increased year on year, but has reduced use of the last resort antibiotics (piperacillin/tazobactam and carbapenems) by 4% between 2015 and 2016. Self-care advice provided by the ‘Keep Antibiotics Working’ campaign in leaflets and materials distributed in GP surgeries and pharmacies across England includes: * ask your pharmacist to recommend medicines to help with symptoms or pain * get plenty of rest * drink enough fluids to avoid feeling thirsty * use paracetamol if you or your child are uncomfortable as a result of fever – which is a sign of the body fighting infection, and normally gets better by itself in most cases * use tissues for your nose and wash your hands frequently to avoid spreading your infection to family and friends. The campaign is part of a wider cross-government strategy to help preserve antibiotics. The government’s UK Five Year Antimicrobial Resistance Strategy 2013 to 2018 set out aims to improve the knowledge and understanding of AMR, conserve and steward the effectiveness of existing treatments, and stimulate the development of new antibiotics, diagnostics and novel therapies. In July 2014, the Prime Minister announced a review of antimicrobial resistance chaired by the economist Jim O’Neill. The subsequent report, published in 2016, recommended a number of actions to be taken globally to manage the rise of antimicrobial resistance, including public awareness campaigns. PHE’s ‘Keep Antibiotics Working’ campaign targets the general public and is aligned Antibiotic Guardian which urges healthcare professionals and engaged members of the public to take one of a number of pledges to help personal and organisational commitment to preserve antibiotics. The discovery of penicillin, one of the world’s first antibiotics, marks a true turning point in human history — when doctors finally had a tool that could completely cure their patients of deadly infectious diseases. Penicillin was discovered in London in September of 1928. Alexander Fleming, the bacteriologist on duty at St. Mary’s Hospital, returned from a summer vacation in Scotland to find a messy lab bench and a good deal more. Upon examining some colonies of Staphylococcus aureus, Dr. Fleming noted that a mold called Penicillium notatum had contaminated his Petri dishes. After carefully placing the dishes under his microscope, he was amazed to find that the mold prevented the normal growth of the staphylococci. Sir Alexander Fleming (1881 – 1955), studying a test tube culture with a hand lens. It took Fleming a few more weeks to grow enough of the persnickety mold so that he was able to confirm his findings. His conclusions turned out to be phenomenal: there was some factor in the Penicillium mold that not only inhibited the growth of the bacteria but, more important, might be harnessed to combat infectious diseases. Fleming famously wrote about that red-letter date: “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.” Fourteen years later, in March 1942, Anne Miller became the first civilian patient to be successfully treated with penicillin, lying near death at New Haven Hospital in Connecticut, after miscarrying and developing an infection that led to blood poisoning. But there is much more to this historic sequence of events. Actually, Fleming had neither the laboratory resources at St. Mary’s nor the chemistry background to take the next giant steps of isolating the active ingredient of the penicillium mold juice, purifying it, figuring out which germs it was effective against, and how to use it. Howard Florey, a professor of pathology who was director of the Sir William Dunn School of Pathology at Oxford University. He was a master at extracting research grants from tight-fisted bureaucrats and an absolute wizard at administering a large laboratory filled with talented but quirky scientists. This landmark work began in 1938 when Florey, who had long been interested in the ways that bacteria and mold naturally kill each other, came across Fleming’s paper on the penicillium mold while leafing through some back issues of The British Journal of Experimental Pathology. Soon after, Florey and his colleagues assembled in his well-stocked laboratory. They decided to unravel the science beneath what Fleming called penicillium’s ”antibacterial action.” A petri-dish of penicillin showing its inhibitory effect on some bacteria but not on others. One of Florey’s brightest employees was a biochemist, Dr. Chain was an abrupt, abrasive and acutely sensitive man who fought constantly with Florey over who deserved credit for developing penicillin. Despite their battles, they produced a series of crude penicillium-mold culture fluid extracts. During the summer of 1940, their experiments centered on a group of 50 mice that they had infected with deadly streptococcus. Half the mice died miserable deaths from overwhelming sepsis. The others, which received penicillin injections, survived. It was at that point that Florey realized that he had enough promising information to test the drug on people. But the problem remained: how to produce enough pure penicillin to treat people. In spite of efforts to increase the yield from the mold cultures, it took 2,000 liters of mold culture fluid to obtain enough pure penicillin to treat a single case of sepsis in a person. In September 1940, an Oxford police constable, Albert Alexander, 48, provided the first test case. Alexander nicked his face working in his rose garden. The scratch, infected with streptococci and staphylococci, spread to his eyes and scalp. Although Alexander was admitted to the Radcliffe Infirmary and treated with doses of sulfa drugs, the infection worsened and resulted in smoldering abscesses in the eye, lungs and shoulder. Florey and Chain heard about the horrible case at high table one evening and, immediately, asked the Radcliffe physicians if they could try their ”purified” penicillin. After five days of injections, Alexander began to recover. But Chain and Florey did not have enough pure penicillin to eradicate the infection, and Alexander ultimately died. A laboratory technician examining flasks of penicillin culture, taken by James Jarche for Illustrated magazine in 1943. Another vital figure in the lab was a biochemist, Dr. Norman Heatley, who used every available container, bottle and bedpan to grow vats of the penicillin mold, suction off the fluid and develop ways to purify the antibiotic. The makeshift mold factory he put together was about as far removed as one could get from the enormous fermentation tanks and sophisticated chemical engineering that characterize modern antibiotic production today. In the summer of 1941, shortly before the United States entered World War II, Florey and Heatley flew to the United States, where they worked with American scientists in Peoria, Ill., to develop a means of mass producing what became known as the wonder drug. Aware that the fungus Penicillium notatum would never yield enough penicillin to treat people reliably, Florey and Heatley searched for a more productive species. One hot summer day, a laboratory assistant, Mary Hunt, arrived with a cantaloupe that she had picked up at the market and that was covered with a ”pretty, golden mold.” Serendipitously, the mold turned out to be the fungus Penicillium chrysogeum, and it yielded 200 times the amount of penicillin as the species that Fleming had described. Yet even that species required enhancing with mutation-causing X-rays and filtration, ultimately producing 1,000 times as much penicillin as the first batches from Penicillium notatum. Throughout history, the major killer in wars had been infection rather than battle injuries. In World War I, the death rate from bacterial pneumonia was 18 percent; in World War II, it fell, to less than 1 percent. From January to May in 1942, 400 million units of pure penicillin were manufactured. By the end of the war, American pharmaceutical companies were producing 650 billion units a month. Ironically, Fleming did little work on penicillin after his initial observations in 1928. Beginning in 1941, after news reporters began to cover the early trials of the antibiotic on people, the unprepossessing and gentle Fleming was lionized as the discoverer of penicillin. And much to the quiet consternation of Florey, the Oxford group’s contributions were virtually ignored. That problem was partially corrected in 1945, when Fleming, Florey, and Chain — but not Heatley — were awarded the Nobel Prize in Physiology or Medicine. In his acceptance speech, Fleming presciently warned that the overuse of penicillin might lead to bacterial resistance. In 1990, Oxford made up for the Nobel committee’s oversight by awarding Heatley the first honorary doctorate of medicine in its 800-year history. Maybe this September 28, as we celebrate Alexander Fleming’s great accomplishment, we will recall that penicillin also required the midwifery of Florey, Chain and Heatley, as well as an army of laboratory workers. Markel about how a particular aspect of modern medicine came to be? Howard Markel revisits moments that changed the course of modern medicine on their anniversaries, like the development of penicillin on Sept. Above: Jean-Claude Fide is treated with penicillin by his mother in 1948. Howard Markel writes a monthly column for the PBS NewsHour, highlighting the anniversary of a momentous event that continues to shape modern medicine. He is the director of the Center for the History of Medicine and the George E. Wantz Distinguished Professor of the History of Medicine at the University of Michigan. The discovery of penicillin, which has saved millions of lives, was made by physician/scientist Alexander Fleming. Born in Scotland in 1881, he eventually moved to London with his family. After completing school, Fleming worked in a shipping office for several years before starting medical school, using money from his share of his uncle’s estate to pay for his education. The captain convinced Fleming to pursue a career in research instead of surgery, so that he could stay at the school. Fleming was taken under the wing of Sir Almroth Wright, a pioneer in immunology and vaccine research. Fleming remained with this research group for his entire career. As an Army Medical Corps captain in World War I, he witnessed many of his fellow soldiers die as a result of uncontrolled infection. At the time, antiseptics were used and often caused more harm than good.
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