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Super bugs

Ten important moments in the history of antibiotic discovery

Starting in the 1930's, scientists began discovering antibiotics. These drugs have gone on to save millions of lives by killing the bugs responsible for infectious diseases. Here are the ten key moments in the discovery of antibiotics.

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von Victoria Parsons

Alexander Fleming discovers penicillin 

Image credit: Monica Arellano-Ongpin licensed under Creative Commons

On September 3, 1928, Fleming returned from holiday and sorted through some petri dishes at St Mary’s Hospital in London, where he was Professor of Bacteriology. The dishes contained a bacteria called Staphylococcus, which causes boils, sore throats and abscesses. One dish stood out. It had a blob of mold on it, and the bacteria around the mold had been killed.

Fleming kept experimenting with his „mold juice“ and found it could kill a range of bacteria. He published the results of his research in 1929. Although it would be many years before penicillin could be isolated from the mold and used as an antibiotic, this marks the discovery of the first true antibiotic.

Source: The American Chemical Society

 “Wonder drug“ penicillin developed for use on soldiers in World War Two 

A glass penicillin fermentation vessel like the ones used by drug company Glaxo between 1940-45 when attempting to mass-produce penicillin. Later, the mold was grown within large industrial fermenters and able to be mass produced. Image credit: Wellcome Images licensed under Creative Commons

After Alexander Fleming discovered it, penicillin largely fell out of scientists minds. It proved very difficult to isolate the drug from the mold. But the few trials that were carried out with it showed that it was hugely effective in treating infections, in mice at least.

With the outbreak of the Second World War, it became obvious that finding a way of mass producing penicillin could save many soldiers lives and be hugely useful. So the US and British government’s challenged the pharmaceutical industry to find a way to mass produce it.

Pharmaceutical companies chose different methods of trying to mass produce penicillin, but ultimately it was Pfizer that was successful – they developed a way of using deep-tank fermentation (a process they had been using to produce citric acid) to make penicillin in bulk. In 2008, Pfizer’s work on this was designated a National Historic Chemical Landmark by the American Chemical Society.

Once penicillin could be mass produced it was given to soldiers heading to Europe; because it was known that infections, not battle wounds, claimed more lives. Scientists manufactured 2.3 million doses of penicillin in time for the D-Day landings, and drug companies in the US distributed posters which proclaimed “Thanks to PENICILLIN… He Will Come Home!“

After the war, mass-production of the wonderdrug began in earnest and it was soon available to civilian patients.

Cephalosporins isolated in 1945

Image credit: Pablo Fernandez licensed under Creative Commons

Like penicillin, the class of antibiotics called cephalosporins came from research that was mostly academic, but then led to results which had a practical, medical application.

Cephalosporium bacteria was first isolated from soil in Sardinia, in 1945, by a scientist called Giuseppe Brotzu, who isolated the bacteria from sewage runoff. However, he lacked the resources to investigate further so sent samples to scientists at Oxford University, UK. The compound was then purified by Edward Abraham and Guy Newton.

After cephalosporin C, as it was called, was discovered in 1953 by the Oxford University scientists they sent it to the United States Further work in the United States led to large-scale production of the drug.

Cephalosporins are broad-spectrum antibiotics, which mean they are effective against a wide range of bacteria. They are used to treat septicaemia, pneumonia, meningitis, biliary-tract infections, peritonitis, and urinary-tract infections. Of the other antibiotics, they are most similar to the penicillins.

Sources: A Glimpse of the Early History of the Cephalosporins, Journal of Clinical Infectious Diseases, and NHS Evidence.

Chloramphenicol discovered in 1947 

Image credit: Brother Magneto licensed under Creative Commons

Chloramphenicol was discovered in soil and compost – a natural product secreted by the bacterium Streptomyces venezuelae. The efficiency of the new antibiotic was soon proved with dramatic results, combating two typhus outbreaks in Bolivia and Malaysia in 1948.

In 1949, chloramphenicol was approved for use by the US Food and Drug Administration as the first broad-spectrum antibiotic. Its use rapidly spread worldwide and it was used extensively in the treatment of infections ranging from acne to bronchitis to bacterial meningitis.

In the 1960’s, chloramphenicols popularity waned as use of the drug was linked to fatalities resulting from its toxic effects on bone marrow. It is now rarely used, due to its toxicity and the availability of effective, alternate antibiotics.

Source: The Journal of Pediatric Pharmacology and Therapeutics

1948: The first tetracyclines

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Discovered as natural products from the soil bacteria actinomycete, research on tetracyclines was first published in 1948.  This new class of antibiotic was noted for their broad spectrum activity – they were effective against a wide range of infections – and they began to be mass produced in the late 1940’s and early 1950’s.

Source: New York Academy of Sciences

Discovery of colistin

Image credit: Nathan Reading licensed under Creative Commons

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Bacteria are tested for sensitivity to antibiotics. This strain of bacteria was only resistant to Colistin, eg. it was resistant to all other antibiotics tested on it.

In 1947 an antibiotic called Polymyxin, in the class of antibiotics called the cyclic polypeptide antibiotics, was discovered. Polymyxin E was produced by soil bacteria, and is also called Colistin – because the soil bacteria that produces it was first called Bacillus polymyxa var. Colistinus, before being renamed Paenibacillus polymyxa.

Colistin has been available since 1959 for treating infections caused by Gram-negative bacteria. However, because it was potentially toxic – and another class of antibiotics, called aminoglycosides, were discovered which worked on the same bacteria but were less toxic – use in humans was massively restricted.

Colistin is now considered a drug of last resort, and is usually reserved to treat bacteria which are already resistant to treatment with other drugs. However, it’s been used to treat farm animals around the world for decades, and resistance to the drug has grown.

Sources: UK Government’s Animal and Plant Health Agency

Aminoglycosides

Image credit: Sanofi Pasteur licensed under Creative Commons. Scanning electron microscope image of mycobacterium tuberculosis, responsible for tuberculosis.

The first aminoglycoside, the antibiotic streptomycin, was discovered in 1943 by American biochemists Selman Waksman, Albert Schatz, and Elizabeth Bugie. They isolated the antibiotic from Streptomyces griseus, a strain of soil bacteria. Streptomycin was found to kill various bugs, including one which causes tuberculosis.

Aminoglycosides were the long sought after remedy to tuberculosis and other serious bacterial infections. However, their potential side effects – they could be toxic to kidneys and ears – meant their use declined in most countries in the 1970s and 1980s, as new antibiotics were discovered which could be used for similar treatment.

Today aminoglycosides are once more one of the most commonly used antibiotics worldwide, because of their high efficiency and low cost. Doctors may be reluctant to use them because of the risk of toxicity, but have little choice because these antibiotics are so powerful.

Source: US National Library of Medicine National Institutes of Health 

The 1950’s: Discovery of macrolides

Image credit: Nathan Reading licensed under Creative Commons

The macrolides were first discovered in the 1950s, when scientists isolated erythromycin from the soil bacteria Streptomyces erythraeus. In the 1970s and 1980s synthetic versions of erythromycin, including clarithromycin and azithromycin, were developed.

Macrolides are used to treat infections caused by the bacteria Streptococcus in people who are allergic to and so can’t be treated with penicillin. Macrolides can also be used to treat penicillin-resistant strains of bacteria.

This family of antibiotics includes erythromycin and clarithromycin, which are particularly useful for treating lung and chest infections. Macrolides are well tolerated, orally available and widely used to treat mild-to-moderate infections.

Source: Encyclopædia Britannica

The emergence of MRSA 

Image credit: NIAID licensed under Creative Commons. Scanning electron micrograph of a human neutrophil ingesting MRSA (purple).

Methicillin-resistant S. aureus was first reported in the UK in 1961, just a year after the antibiotic methicillin was introduced in the country. S. aureus was already resistant to penicillin, and when the bug became resistant to methicillin as well it became the first superbug – a bacteria that is resistant to multiple antibiotics.

MRSA remained uncommon in the UK for several years after it was first discovered, but then slowly the number of cases increased. In the 2000’s there were several outbreaks of MRSA infections in UK hospitals, causing thousands of deaths.

It’s hard to put a figure on how many cases of MRSA there are globally, and how many deaths. But in the US alone the Centers for Disease Control and Prevention estimates there are more than 80,000 invasive MRSA infections and over 11,000 deaths every year.

Source: Journal of Antimicrobial Chemotherapy

The quinolones – not isolated from soil but made by chemists

Image credit: Marc Perkins licensed under Creative Commons. A slide of gram-stained Bacillus megaterium seen at approximately 1,000x magnification. This bacterium is a gram-positive bacillus that is in the streptobacillus form (growing in long chains).

Unlike many of the other antibiotics discovered during the middle of the last century, the quinolone class of antibiotics was not isolated from bacteria in the soil but made, synthetically, by chemists.

The discovery of the quinolones began accidentally, in 1962, as a byproduct of some research on the antimalarial drug chloroquine. The accidental discovery led to prolific research on quinolones and the development of a library quinolone compounds.

The quinolones are a very useful class of antibiotics which can be used against both gram positive and gram negative bacteria.

Source: The Quinolones: Past, Present, and Future, Journal of Clinical Infectious Diseases

bacteria

Super bugs

Seven things YOU can do to combat antibiotic resistance

Antibiotic resistance is one of the biggest public health threats of our time. CORRECTIV reporters have been covering superbugs for more than two years. Here are the seven things they've learned that we can all do to help fight drug resistant bugs.

read more 5 minutes

von Victoria Parsons

1. Wash your hands

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Wash them properly. Every time your hands look visibly dirty, after every time you use the bathroom, and every time before you eat or prepare food.

Washing your hands reduces the spread of bacteria and protects you from infections. Cleaning them regularly is one of the best ways to avoid getting sick, and stops the spread of bugs from you to the people you come into contact with.

Read more of CORRECTIV’s tips on hand washing here.

2. Do what your doctor says when you’re prescribed antibiotics

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For decades, the advice has been that it’s essential that you finish taking your prescribed course of antibiotics, even if you feel better and your symptoms have gone away.

This was said to be because if you stop taking an antibiotic partway through the treatment it gives the bug an opportunity to develop resistance to the antibiotic. This resistant bug can then spread, making the antibiotics less effective in treating them.

However, some scientists are now questioning this longstanding refrain. They say that actually, you should stop taking the antibiotics as soon as you feel better – because any exposure of the bugs to the drugs creates resistance.

Our take on this? Follow the instructions your doctor gives you when he prescribes antibiotics. And maybe ask him what he thinks about the debate over this bit of science.

Source: UK National Health Service

3. Cook and handle meat properly

Photo credit: Kyle Brammer licensed under Creative Commons

Some antibiotic-resistant infections come from food – like salmonella, campylobacter and E. Coli. When farm animals are given antibiotics, bugs that are resistant to the drugs can survive treatment. These resistant bugs can multiply in the animals guts and remain on the meat.

Raw meat can contaminate your meal with resistant germs. When cooking meat, wash your hands before and after. Handle the meat properly: don’t use chopping boards or knives that have touched uncooked meat on other parts of the meal.

Raw meat must be stored at a low enough temperature. Don’t handle raw meat if you have open cuts on your hands. Read more of CORRECTIV’s tips on handling raw meat here.

Source: CDC

4. Take care when visiting friends and family in hospital

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You should wash your hands before you enter their room and after you leave it. This helps avoid spreading germs around the hospital.

Doctors and nurses should also wash their hands before touching every patient – and it’s okay to check that they’ve done this. In fact, in the United States, hospitals encourage patients to ask their doctors if they’ve washed their hands. Some doctors and nurses even wear badges to show they want to be asked and reminded.

Be aware that wearing rings or fake fingernails gives bugs a good spot to hide. Make sure you wash these very carefully.

Read more hospital visiting tips from CORRECTIV here.

5. Think twice before requesting antibiotics for a cough or a cold

Photo credit: Rebecca Brown licensed under Creative Commons

Viral infections like coughs and colds, flu, sore throats and bronchitis cannot be treated with antibiotics. Antibiotics do not fight infections that are caused by viruses directly, only those that are caused by bacteria.

To combat antibiotic resistance we all have to use antibiotics appropriately and responsibly. If you take antibiotics for a cough, sore throat or flu, they usually won’t make you feel better. They also won’t stop other people from catching your cold, and you may end up contributing to the problem of antibiotic resistance.

This is because you’ll kill harmless bacteria when you take antibiotics for your cold, and leave antibiotic-resistant bacteria behind. These resistant bugs can then spread.

Source: CDC

6. Stay up to date with vaccinations

Photo credit: NIAID licensed under Creative Commons

Staying healthy and preventing disease is key to fighting antibiotic resistance. It’s better to prevent a disease than to treat it.

Vaccines protect you and the people you come into contact with. Many of the infectious disease that were once common – like polio, measles, whooping cough, German measles, mumps and tetanus – are now controlled with vaccinations. Vaccines have prevented countless cases of infectious disease and saved millions of lives.

Keep your vaccines up to date, and if you travel abroad check to see if you need vaccinations. Make sure you get them in time.

Source: CDC

7. Prevent the spread of Sexually Transmitted Infections

Photo credit: Jenny Koske licensed under Creative Commons

Common sexually transmitted infections (STI’s) like chlamydia, gonorrhea and syphilis are caused by bacteria and usually treated with antibiotics. However, these STI’s are becoming more difficult to treat. This is because they are often undiagnosed, and because the antibiotics used to treat them are beginning to fail.

Resistance has increased rapidly in recent years, especially with gonorrhea. Strains of multi-drug resistant gonorrhea that do not respond to any available antibiotic have been detected by doctors. Untreated or untreatable STI’s can have serious, long term consequences on your health.

Reduce your risk of catching an STI. Use protection with your partner, get tested regularly, and know the symptoms. Learn more about drug-resistant STI’s and what you can do to combat them here.

Source: WHO and CDC

rs942_gb_clown

Super bugs

Top Priority Antibiotic Resistance

In Great Britain, superbugs have been in the center of attention since some well publicised outbreaks. Government initiatives aim to tackle the issue, but problems, like the lack of reliable data, remain. Here we provide an overview over the complex situation in the country and help you to get the most relevant information.

von Victoria Parsons , Andrew Wasley

Antibiotic resistance has become a prominent topic in British politics. In 2014 the UK government launched the AMR review as a high-profile, high-level response to the serious concerns being raised about antibiotic resistance. 

The Review, led by former Goldman Sachs economist Lord Jim O’Neill, has focused largely on the issue as a global health crisis and has produced recommendations on how to tackle the problem at an international level. 

In a recent exclusive interview with the Bureau, Lord O’Neill said that the antibiotics crisis is a „more troubling train wreck“ than the global financial crash of 2008. He also floated the idea of an „antibiotics tax“, which was one of several options explored by the Review in their recent and final report.

The UK’s chief medical officer, Dame Sally Davies, has described the problem of antibiotic resistance as a „ticking time bomb“ that should be ranked along with terrorism on a list of threats to the nation.

In 2013 the Government launched the cross-party Five Year Antimicrobial Resistance Strategy. The Strategy is focusing on three strands: improving knowledge and understanding of antimicrobial resistance; conserving existing antibiotics; and stimulating the developments of new antibiotics.

High awareness after serious outbreaks 

The awareness stems partly from a series of serious outbreaks of MRSA in the mid-2000s. The outbreaks reached a peak in 2006 when MRSA caused or contributed to 1,652 deaths – five times the number in 1993 when records began. Several policy changes have tightened up on cleanliness in hospitals and the number of deaths has fallen in recent years.

New infection control guidelines for nursing staff in 2005 included screening hospital patients for MRSA, better hygiene practices and putting contagious patients in isolation rooms. 

Hospitals must now report the numbers of MRSA infections – and make these available to the public. Since 2012, when the number of MRSA related deaths was fewer than 300, the records have shown the number of MRSA infections each year instead of deaths. 

In addition the UK government has run several public awareness campaigns around the use of antibiotics, including telling people not to ask their doctors for antibiotics for a common cough or cold because antibiotics do not help fight viral infections. 

Incomplete reporting

The government publishes data for cases of the most common, and what it considers to be the most dangerous, infections.

Campylobacter is the most common food poisoning infection in the UK, thought to be responsible for at least 280,000 cases a year and around 100 deaths.

While antibiotics will work in many cases, a Bureau investigation in April this year found that resistance to one of the key antibiotics used to treat campylobacter infection – ciprofloxacin – is steadily increasing. In 2015, almost one in two of all human campylobacter cases tested in England for resistance to ciprofloxacin – one of several drugs doctors turn to when victims of the food poisoning bug develop complications – returned positive results.

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Public Health England publishes annual, monthly and quarterly data on E. coli, C. difficile, and MRSA infections, but there is no information on what proportion of these cases are resistant to some or all antibiotics. This infection data is broken down either by hospital or by clinical commissioning group – National Health Service bodies responsible for the planning and commissioning of health care services for their local area.

Data collected by European Centre for Disease Prevention and Control, which analyses samples from participating hospitals, puts the UK in the lower average for the proportion of resistant strains of E. coli and Staphylococcus aureus or MRSA

Unclear trend in consumption

The most recent data shows that in 2013, humans were dispensed a total of 531.2 tonnes of antibiotics while total sales for animal use was 418.7 tonnes. When broken down to biomass, Human consumption of antibiotics was the equivalent of 135mg per kg of person, whereas sales of antibiotics for use in food producing animals equated to 55.6mg per kg.

This puts the UK at the mean of the continent: The European average was 116mg in humans and 144mg in animals according to a report by the European Commission from 2015 that analysed data from 2012. When it comes to total consumption, the UK came in at third place after France and Italy, mostly owing to its large populace.

In 2014, more than 37 million antibiotic „items“ were prescribed by doctors in general practice. An item refers to a single supply of an antibiotic on a prescription form – which tells us how many antibiotic prescriptions there were, but doesn’t indicate the length of treatment or dose prescribed. The three groups of antibiotics most frequently used in England that year were penicillins (45 percent), tetracyclines (22 percent) and macrolides (15 percent).

Although the number of prescriptions for antibiotics written by doctors has gone down in recent years, a report from Public Health England in 2015 found that the consumption of antibiotics had actually gone up 6.5 percent between 2011 and 2014. This suggests that longer prescriptions or higher doses of antibiotics are being prescribed by doctors, who prescribe around 74 percent of antibiotics to patients.

When it comes to transparency of antibiotic prescriptions in doctors’ offices, England is ahead of other European countries. The prescription data for every individual doctor’s office is public – and can for example be used for statistical and scientific analyses.

In hospitals antibiotic prescribing also increased significantly between 2011 and 2014, up 11.7 percent in hospital inpatients and 8.5 percent in outpatients. The Public Health England report also found that hospitals were prescribing the highest proportion of broad-spectrum antibiotics. This is problematic because, according to The National Institute for Health and Care Excellence, broad-spectrum antibiotics should only be used when infections are already resistant – if they are routinely prescribed, they increase the risk of MRSA and other resistant bugs.

As discovered by the Bureau, even the government only has a partial view of what is used by the farming industry. The Veterinary Medicines Directorate publishes an annual report on sales of antibiotics for use in animals, based on data from animal pharmaceutical companies. 

More transparency is required so we can see where the problem lies. In February the Bureau published an investigation which showed that the use of a critically important class of antibiotics called fluoroquinolones had increased by 59 percent in UK poultry farming between 2013 and 2014. 

The Veterinary Medicines Directorate data shows that total antibiotic sales (in a metric that allows for varying numbers of livestock over time) gradually increased between 2008 and 2014, while sales of antibiotics that are critically important in human medicines – like fluoroquinolones and 3rd and 4th generation cephalosporins – increased more sharply.

We are working on getting access to more detailed data so we can create a bigger picture of which antibiotics are being used and where, to better our understanding of the problem.


The authors are journalists at „The Bureau of Investigative Journalism“, a British independent not-for-profit newsroom, with whom we collaborate on superbugs investigations

Graveyard: 10 million people will supposedly die of drug-resistant germs

Graveyard: 10 million people will supposedly die of drug-resistant germs© Ivo Mayr

Super bugs

Projected death toll from drug-resistant superbugs ‘based on incomplete data and flawed assumptions’

An official estimate of the massive number of deaths that will be caused each year by antimicrobial resistance – and cited widely by the UN and world leaders – is “unreliable” and “undermines” the fight against superbugs, a new scientific study has warned.

read more 10 minutes

von Hristio Boytchev , Victoria Parsons

This investigation appears together with “The Independent“ and in German with „Spiegel online


An official estimate of deaths expected to be caused annually by antimicrobial resistance – cited by the United Nations and world leaders – is „unreliable“ and undermines the fight against superbugs, a group scientists has warned.

Antimicrobial resistance (AMR) arises when micro-organisms that cause an infection survive medicine that is intended to kill them or stop their growth.

A figure of „10 million“ deaths a year has been widely used to illustrate the dangers of not taking action on AMR, but leading scientists now say it is based on incomplete data and flawed assumptions.

The number first appeared in 2014, in the initial report of the Review on Antimicrobial Resistance – a body set up by former Prime Minister David Cameron and headed by the economist Lord Jim O’Neill.

The aim of the AMR Review was to analyse the potential impact to human health of growing resistance to antibiotics and antivirals.

It warned that without urgent action, by 2050 a further 10 million people around the world would lose their lives to drug-resistant infections – a figure that has been cited for the past two years by media organisations, politicians, the UN, the European Commission, the World Health Organisation, the G7, and many others. 

The number also has prompted headlines warning of an “antibiotic apocalypse“, in which superbugs would “kill more than cancer“ – and a world that’s on the cusp of a “post-antibiotic era“.

Now scientists, led by Marlieke de Kraker at the HUG (Geneva University Hospitals), say that while the dangers of the overuse of antibiotics are undisputed, the 2014 death toll estimate does not stand up to scientific scrutiny.

In a peer-reviewed article, published in the scientific journal PLOS Medicine, the researchers acknowledge that action is required to fight antibiotic resistance, but recommend that „estimates for such an important, ‘hot’ topic should undergo scrutiny by independent experts before being made publicly available“.

“We contend that unreliable global estimates like those provided in the AMR Review potentially undermine, rather than support, the fight against a post-antibiotic era“, the study’s authors conclude.

Speaking to correctiv.org, Ms de Kraker said her article had been well-received by the scientific community – many had long doubted the figure and are reportedly glad it has finally been disputed.

Petra Gastmeier, director of the Institute of Hygiene and Environmental Medicine at the Charité University Hospital in Berlin – not involved in the study – agreed with its conclusions, saying „the authors have shown the mistakes of the British study step-by-step“.

But neither scientist would provide their own estimates, saying there were too many uncertainties and not enough data.

Lord O’Neill, who was the first minister to resign from Theresa May’s new Government – two days after presenting the Review’s findings to a major summit of the UN in New York – said the AMR Review no longer existed in a formal capacity, but was keen to comment on the new findings.

He said: „Two specialist forecasting organisations put these numbers together for us about the possible future consequences of inaction, and this work has helped spur huge momentum on AMR in the UK and internationally in the last two years, which continues.

“One of my Review’s 10 specific calls was for improved surveillance to get better data to continue to assess this huge health and economic threat so in that sense we agree on the need for better data.“

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Consulting giant KPMG was one of the two forecasting organisations mentioned by Lord O’Neill. A KPMG spokesperson said: „Our own analysis was based on assumptions and the best data available at the time. Since then more data has become available and we are looking to update our estimates next year.“

When David Cameron commissioned the review in 2014, he warned that antibiotic resistance could lead to medical „dark ages“. He said it was one of the gravest crises the world faced.

Lord O’Neill, a former senior Goldman Sachs banker with a worldwide reputation as a top economist, was asked to head the review – and in 2015 he issued a call for urgent action.

But according to the PLOS Medicine study, Lord O’Neill’s AMR Review contained three main errors.

The scientists led by Marlieke de Kraker found the Review’s global deaths estimate not credible because it was based on incomplete data from the European Antimicrobial Resistance Network (EARS-Net), which records instances of infections in 895 European hospitals.

The new study argues this data is not representative of infections across Europe as a whole. This is because a third of the hospitals that report to EARS-Net are large specialist hospitals, whose patients will naturally be carrying more infections than patients in, for example, a smaller hospital or a GP’s surgery.

The AMR Review had extrapolated infections data from the 895 European hospitals to calculate the global number of infections, which the new study calls „a crude approach“.

Fears over antibiotic usage leading to lethal infections were discussed by the G8 in 2013

Suppose that 2,000 patients die from a resistant strain from a bug such as MRSA, and 1,000 patients with a treatable, non-resistant strain also die. It would be reasonable to assume the deadliness of the resistant bug is twice as high. It was precisely this assumption the Review made – according to Ms de Kraker’s team who contest it.

Charité University Hospital’s Petra Gastmeier explained that the two groups of patients were different. She said the MRSA deaths will be, on average, older – and therefore at a bigger risk of serious illness and death than those who are infected with the non-resistant bug.

The older people are, the more antibiotics they are likely to have taken – increasing the likelihood of them carrying resistant bugs, she added.

While infections with resistant bugs can result in death, the risk is probably lower than what the Review had assumed.

Based on these assumptions, the Review used a figure of 700,000 deaths a year from antimicrobial resistance as its baseline. And then, „based on [these] already uncertain… estimates“, the PLOS Medicine study suggests that the Review’s final error was assumptions about increasing infection rates in the future.

According to the study, there is already evidence that fewer people are dying from infections because of better medical care. The 10 million figure was calculated based on the AMR Review’s assumption that resistant bugs will become significantly more common and twice as infectious, and that the proportion of people who die from these infections will not change – even though, as the study points out, improvements in public health systems, especially in middle-income countries, mean that even now the number of people who die from such infections is getting smaller.  

While the study acknowledges that the Review did call for better data and better surveillance of infections, it also says that the Review did not clearly report „how existing uncertainties in each of the applied steps could affect their estimates.“

The scientists said: „The Review estimated that antimicrobial resistance could cause 10 million deaths a year by 2050. This estimate has become a familiar refrain. It has been quoted repeatedly by lay media, experts, and public health agencies. Frequently, only this specific, frightening conclusion is reproduced from the report, unaccompanied by caveats or confidence intervals… We contend that unreliable global estimates like those provided in the AMR Review potentially undermine, rather than support, the fight against a post-antibiotic era.“

A Department of Health spokesperson said: „The figures in Lord O’Neill’s report are predictions based on a number of assumptions about current and future trends. They serve as a warning as to what might happen if we don’t act now – and there is certainly consensus from experts across the world that the threat from antimicrobial resistance is very real.“

© Ivo Mayr

Super bugs

Less than half of antibiotics used in hospitals worldwide are prescribed appropriately, confirms a comprehensive new study

A new meta-analysis from a team of Cochrane scientists looked at 221 studies to assess the effectiveness and safety of interventions which try to improve how doctors prescribe antibiotics to in-patients. The analysis also identified ways of reducing unnecessary use of antibiotics in hospitals.

read more 4 minutes

von Hristio Boytchev , Victoria Parsons

A wide variety of interventions were found to safely reduce unnecessary antibiotic use in hospitals, according to a new update from a meta-analysis which has been running for 15 years.

The update found that in hospitals antibiotics are only prescribed according to medically recommended guidelines 43 per cent of the time. This means that in more than half of the cases where antibiotics were used, hospital doctors prescribed them outside of the guidelines.

When antibiotics are used too often or incorrectly, this leads to the development of resistant bacteria. In Germany it’s estimated that between one and four thousand people die in hospital from antibiotic resistant infections every year.

Why aren’t the doctors following the guidelines?

“Valium for Surgeons“

Many surgeons prescribe antibiotics as a precaution during surgery, says Hajo Grundmann, Head of Hospital Hygiene at the University Hospital of Freiburg. He says that surgeons administer antibiotics as a „reassurance“ days after surgery has been completed, in contradiction to the guidelines which says antibiotics should be administered at most a few hours before and after surgery to prevent infection.

Grundmann says that „antibiotics are the valium for surgeons“ because they bring peace of mind, but adds that there is another factor: many hospitals are now profitable companies. This puts the doctors under greater pressure. Their performance is measured not just in terms of whether the operations are successful, but whether they’re earning money for the hospital. When it comes to efforts to prescribe antibiotics „sparingly“ Grundmann says this may play a role.

The new study also demonstrated that it’s possible to change the prescribing behaviour of doctors through interventions. These can include monitoring, training and supervising doctors when it comes to their use of antibiotics – and according to the study, these interventions can improve appropriate prescribing rates by 15 per cent.

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Grundmann says that the difference, from 43 per cent appropriate prescribing without any interventions, to 58 per cent appropriate prescribing with interventions, is great. It’s a clear sign, he says, that it’s possible to change doctors behaviour without medically disadvantaging the patient. The study also showed that prescribing antibiotics within the guidelines could reduce a patient’s hospital stay by one day – reducing their chances of picking up an infection in hospital.

But 58 per cent of antibiotic prescribing falling with guidelines still means that a third of antibiotics in hospitals will be prescribed inappropriately. Winfried Kern, Professor of Infectiology at the University Hospital of Freiburg, says that unfortunately it’s not realistic to expect 100 per cent of prescribing to be within the guidelines. There are many medical situations, he says, where there is no guideline or where it would be medically sensible to deviate from the guideline – for example, if a patient is particularly susceptible to a certain antibiotic.

“And more than this, the guidelines are not always that good“, Kern added.

The study was published by a team led by Peter Davey at Dundee University, and looked in detail at how and why different interventions work. Davey said that one problem is that interventions are often vague and unconcrete, and do not have precise objectives. Sometimes the aim is to „follow the guidelines more often“, rather than trying to get appropriate prescribing up to 80 per cent, for example. This makes it difficult to increase appropriate prescribing and difficult to quantify successful interventions.

The least effective kind of intervention, Davey said, was to make doctors fill out a form before they could administer antibiotics to a patient. Often this would make the doctor feel patronised, and they might then fudge the form in order to get the antibiotics for the patient. Training events on antibiotic prescribing were also ineffective, he said.

But in Germany, the focus has been on training. „If something doesn’t work, there is training afterwards“, says Petra Gastmeier, a senior hygienist at the Berlin Charité hospital. There isn’t a lack of knowledge in Germany – the doctors, in theory, know what they are supposed to do.

According to Gastmeier, in the English speaking world more progress has been made. Infection specialists, surgeons and other doctors are often supervised and given feedback on their prescribing behaviour.

Gastmeier is now working on a project in Germany which should also encourage paramedics to prescribe antibiotics more appropriately. The situation in ambulances is similar to that in hospitals, she says.