In a new study, published in Nature, German researchers with the European Molecular Biology Laboratory (EMBL) report that more than a quarter of the non-antibiotic drugs they tested – including acid-reducing medications, antivirals, blood-pressure medications, anti-psychotics and chemotherapy drugs – inhibited the growth of at least one strain of bacteria commonly found in the gut of healthy humans.

Another worrying finding was that consumption of some non-antibiotics could promote antibiotic resistance.

Collateral Damage

The human gut contains a large number of species of bacteria, collectively referred to as the gut microbiome. In the last decade, it has become clear that the composition of the gut microbiome affects human health. It is well-known that antibiotics have a large impact on this microbiome, for example causing gastrointestinal side effects.

Recently, a few commonly used non-antibiotic drugs have been shown to cause changes in gut microbiome composition, but the full extent of this phenomenon was unknown until now.

“The number of unrelated drugs that hit gut microbes as collateral damage was surprising,” said corresponding author and EMBL senior scientist Peer Bork, PhD. “This shift in the composition of our gut bacteria contributes to drug side-effects, but might also be part of the drugs’ beneficial action.”

Common drugs, unexpected impacts

The research team screened 1,079 drugs (156 of which had known antibacterial activity) on 40 representative bacteria from the human gut and monitored effects on bacterial growth. These non-antibiotic drugs tested were intended to target human cells rather than microbial cells, yet the scientists found that more than a quarter of the non-antibiotics (250 out of 923) affect the growth of at least one species in the gut microbiome of healthy individuals, including Escherichia coli, Bacteroides fragilis, and Clostridium difficile.

The non-antibiotic drugs tested included drugs like omeprazole, a proton-pump inhibitor sold under the brand-name Prilosec; loxapine, which is used to treat schizophrenia; and metformin, an antidiabetic drug. The researchers suspect that the antimicrobial effects of some of these drugs, like metformin, could be directly related to their mechanism of action.

Chemotherapy drugs, calcium-channel blockers (used to treat high blood pressure), and antipsychotics inhibited more gut bacteria than other medications. With some drugs, such as antipsychotics, the impact on gut bacteria could possibly enhance their therapeutic effect, the researchers say.

Although the bacterial species’ susceptibility to the drugs varied, the researchers report that the species that are most abundant in the gut of healthy individuals were more susceptible, including species like Roseburia intestinalis, Eubacterium rectale, and Bacteroides vulgaris.

“This suggests that human-targeted drugs have an even larger impact to the gut microbiome with key species related to healthy status,” the authors write.

Promoting antibiotic resistance

The researchers also uncovered a previously unnoticed risk; that consumption of non-antibiotic drugs may promote antibiotic resistance, in part because the general resistance mechanisms of microbes to human-targeted drugs and to antibiotics seem to overlap.

Finding that there was a strong correlation between the bacteria that were resistant to antibiotics and those that were resistant human-targeted drugs, the researchers experimented with a strain of E coli that carries the antibiotic-resistance gene tolC, which produces a protein that flushes antibiotics and other chemicals out of bacterial cells.

Strains of E coli in which this gene was active were resistant both to antibiotics and six of seven non-antibiotics tested, while E coli lacking the gene were more sensitive to both.

This is a serious and worrying finding given that as a population we take many non-antibiotic drugs – for example acid-reducing medications or blood-pressure drugs – often for long periods of time. Doing so, say the researchers could promote antibiotic resistance by inhibiting susceptible strains of bacteria and allowing drug-resistant strains to flourish.

Underestimating the damage

“Taking into account that abundant members of the human gut microbiome are impacted more by drugs, one could speculate that pharmaceuticals, used regularly in our times, may be contributing to the decrease in the diversity of microbiomes of modern western societies,” the researchers conclude.

Since only a fraction of the hundreds of bacterial species in the human gut were tested, the authors say the number of non-antibiotic drugs that inhibit bacterial growth is likely higher, which highlights the urgent need to examine the role that these drugs are potentially playing in microbiome-related diseases and in the global rise of antibiotic resistance.

In an effort to identify factors that might enhance patient safety and post-marketing surveillance efforts, the team analysed data on new drugs approved between 2001 and 2010, with follow up through 2017.

They found that 71 of the 222 drugs put on the market during that time were withdrawn, required a “black box” warning about serious adverse effects, or warranted a safety announcement about new risks to the public. While most of the safety concerns are not serious enough to require withdrawal of a drug from the market, the finding highlights the need for ongoing surveillance of new drugs in the post-market period, said the researchers in the Journal of the American Medical Association (JAMA).

Not enough time

To assess new drugs for safety and effectiveness, the FDA relies on premarket drug testing and clinical trials. Most of the trials are funded by the drug manufacturers themselves and involve fewer than 1,000 patients studied over a period of six months or less. This makes it very difficult to detect long-term safety issues that could potentially affect large numbers of people.

These issues rarely led to a drug withdrawal, said co-author and associate professor of medicine and public health Dr. Joseph Ross. More commonly it was “a black box warning, or drug safety communication issued by the FDA to let physicians and patients know that new safety information has been determined.”

The researchers found that it took a median of 4.2 years after the drugs were approved for safety concerns to come to light, and issues were more common among psychiatric drugs, biologic drugs, and drugs that were approved near the regulatory deadline for approval.

Drugs ushered through the FDA’s fast-track approval process were also among those that had higher rates of safety interventions. These approvals typically look for outcomes other than patient survival, such as changes in tumour size, to determine whether the drugs worked.

The consequences of fast-tracking

The current analysis comes at a time when US President Trump has stated that he wants the Food and Drug Administration to cut the red tape and approve drugs faster.

The findings of the analysis show “that there is the potential for compromising patient safety when drug evaluation is persistently sped up,” added Ross.

“The fact that so many new safety risks are being identified after FDA approval indicates that the FDA is taking its responsibility of ensuring the safety of new drugs throughout their lifetime seriously,” said Nicholas Downing, MD, lead author of the study. “However, these safety risks emerge, on average, four years after approval. This means that many patients are exposed to these medications before the risks become clear.”

The researchers say they hope their data will help inform the ongoing debate about premarket drug evaluation.

Based on real world data from four European countries and almost 10 million people using a full range of non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors (a new generation of NSAID commonly prescribed for arthritis pain).

The landmark analysis in the British Medical Journal found that NSAIDs raise risk of hospital admission for heart failure and that the magnitude of risk varied between individual NSAIDs and according to the dose prescribed.

Although not the first study to show such an association it is certainly one of the largest.

9 common drugs implicated

The risk of admission for heart failure increased for seven traditional NSAIDs (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and two COX-2 inhibitors (etoricoxib and rofecoxib). The increased risk of hospital admission ranged from 16% for naproxen to 83% for ketorolac.

Overall, the researchers found current NSAID users (defined as individuals who had used NSAIDs within the past 14 days) were 19% more likely to be admitted to the hospital with heart failure than past users (individuals who had not used NSAIDs for at least 183 days).

A particular of concern was that commonly used NSAIDS such as ibuprofen, diclofenac, and naproxen were all associated with increased risk of heart failure and that use of high doses of ibuprofen and diclofenac doubled the odds, though the increased risk associated with use of high dose naproxen was slightly lower.

By contrast with other selective COX-2 inhibitors (eg, rofecoxib, etirocoxib), celecoxib were not associated with increased risk of heart failure. But celecoxib was used mostly in low doses, so the safety of higher doses of celecoxib remains unexplored.

The researchers say that the new data “offers further evidence that the most frequently used individual traditional NSAIDs and selective COX 2 inhibitors are associated with an increased risk of hospital admission for heart failure. Moreover, the risk seems to vary between drugs and according to the dose.”

Previous studies highlight problems

Several studies have previously shows links between NSAIDs and health problems.

Earlier this year an analysis in the European Heart Journal found that Cox-2 inhibitors also increased the risk of other health problems including ulcers and increased blood pressure.

A 2014 study in BMJ Open found a significant increase in irregular heartbeat (atrial fibrilliation) in older adults taking NSAIDs. Current use was associated with a 76% greater risk of atrial fibrillation than never use, after taking account of other risk factors, such as age, sex, and underlying cardiovascular problems. Similarly, recent use (with the preceding 30 days) of these drugs was linked to an 84% greater risk of atrial fibrillation.

Also in 2014 an analysis in the journal Rheumatology found that NSAID use (aspirin and ibuprofen) almost double the risk for deep vein thrombosis (DVT) and pulmonary embolism, two lethal conditions.

An accompanying editorial to the latest study says “NSAIDs were first introduced over a century ago and most of the commonly used NSAIDs were registered in an era with few requirements for safety documentation. Therefore, for most of these drugs, there is an alarming lack of randomised studies addressing their safety.”

The research found soaring levels of resistance in chicken meat, with 24% of samples testing positive for ESBL E. coli, a type of E. coli resistant to the ‘critically important’ modern cephalosporin antibiotics. This is four times higher than was found during a similar study in 2015, in which just 6% of chicken tested positive for ESBL E. coli. Modern cephalosporins are widely used for treating life-threatening E.coli blood poisoning in humans.

The study is the first to examine UK-origin non-organic retail meat for resistance to a wide range of important antibiotics for treating E. coli infections. It found very high levels of resistance to two more highly important antibiotics.

A staggering 51% of the E. coli from pork and poultry samples were resistant to the antibiotic trimethoprim, which is used to treat over half of lower urinary-tract infections. In addition, 19% of the E. coli were resistant to gentamicin, a very important human antibiotic used to treat more serious upper urinary-tract infections.

Supermarket polices need to change

The study, commissioned by the Alliance to Save our Antibiotics and carried out by scientists at Cambridge University, looked at 189 UK-origin pig and poultry meat samples from the seven largest supermarkets in the UK (ASDA, Aldi, Coop, Morrisons, Sainsbury’s, Tesco and Waitrose).

It tested for the presence of E. coli which are resistant to the key antibiotics for treating E. coli urinary-tract and blood-poisoning infections in people. The highly resistant ESBL E. coli was found on meat from all of the supermarkets.

The findings provide further evidence that the overuse of antibiotics used to mass medicate livestock on British farms is likely to be undermining the treatment of E. coli urinary-tract and blood-poisoning infections in humans. Some of the antibiotics tested are used in far greater quantities in livestock farming than in human medicine.

This is important because scientists have proven that the use of a veterinary aminoglycoside called apramycin is very likely to have contributed to gentamicin resistance in human E. coli infections. [See studies here and here].

Emma Rose of the Alliance to Save our Antibiotics said: “These findings show the level of antibiotic resistance on retail meat to be worse than expected. Supermarkets must now publicly commit to polices which prohibit the routine mass-medication of groups of healthy animals, and take immediate steps to reduce farm use of the ‘Critically Important’ drugs.”

Dr Mark Holmes, from Cambridge University, who led the study said: “I’m concerned that insufficient resources are being put into the surveillance of antibiotic resistance in farm animals and retail meat. We don’t know if these levels are rising or falling in the absence of an effective monitoring system. These results highlight the need for improvements in antibiotic stewardship in veterinary medicine. While some progress has been made we must not be complacent as it may take many years before we see significant reductions in the numbers of antibiotic-resistant bacteria found in farms.”

Humans at risk

E-coli is by far the most common cause of urinary-tract infections and of dangerous blood poisoning, and can also cause meningitis. These infections must be treated with antibiotics.

Figures compiled by the Alliance from official data (acquired through Freedom of Information requests to submitted to Public Health England, Northern Ireland’s Public Health Agency, Public Health Wales and Health Protection Scotland) show that the number of E. coli blood-poisoning infections has been increasing for the past 25 years and reached a record 45,666 in 2015.

The increase is partly being driven by increasing resistance to key antibiotics in urinary-tract infections, resulting in more treatment failures and in some cases the development of serious blood-poisoning infections. No new antibiotics have been discovered for treating E. coli for 35 years.

Routine use on the farm

The overuse of antibiotics in human medicine is part of the problem, but increasing scientific evidence from a wide range of studies shows that the routine dosing of animals on intensive farms raised in disease-inducing conditions, is also an important contributor.

Dr Ron Daniels BEM, CEO of the UK Sepsis Trust said: “This study highlights a worrying trend towards rising resistance in E.coli on UK retail meat. E.coli in people is the greatest cause of deaths from sepsis, and poor antimicrobial stewardship in intensive farming is undoubtedly contributing to this trend. It’s of paramount importance that we act decisively to reduce this immediate threat to human life.”

The Alliance has raised the issue of farm-antibiotic use with all major retailers over the last few years, and has seen positive progress from Waitrose, who in 2015 stated that antibiotics would not be used for routine prophylaxis within its supply chains.

In August 2016, Waitrose updated their policy to also state that they are working towards significant year on year reductions in usage of all antibiotics, and have pledged to end the use of all CIAs as soon as possible.

In response to the testing, the Alliance is calling for similar action from all UK supermarkets to tackle the use of antibiotics in their supply chains, by banning the routine preventative mass-medication of groups of animals, and dramatically curbing farm-use of the ‘critically important’ antibiotics. The global network Avaaz has also launched a petition calling for urgent action.

Philip Lymbery, Compassion in World Farming’s CEO, said: “This new study reveals our worst fears: without a drastic change in the over-use of antibiotics on factory farms, we could be facing a post-antibiotic era. We must no longer sacrifice animal welfare for the sake of producing cheap meat.”

Peter Melchett, policy director at the Soil Association said: “These results show how vital it is to encourage farming systems that keep animals healthy without abusing medicines that are crucial to human health. Organic farmers have been doing this successfully for years. Supermarkets must act to protect public health and support farmers to change their farming systems.”

• The testing was carried out by Dr Mark Holmes – Reader in Microbial Genomics & Veterinary Science at the University of Cambridge. A full briefing of the findings, “Antibiotic-resistant E. coli on supermarket meat – a serious threat to human health”, is available here.
• To learn more about natural alternatives to antibiotics see our article Antibiotic alternatives – your 12-point plan.

Early exposure to these powerful drugs is associated with an increase in food allergy diagnosis, new research from the University of South Carolina suggests.

The researchers from the College of Pharmacy, School of Medicine and Arnold School of Public Health used South Carolina Medicaid administrative data from 2007 to 2009 to identify children with food allergies and compared these to a control group taken from the same dataset, who had no food allergies.

Even after adjusting for factors including birth, breastfeeding, asthma, eczema, maternal age and urban residence, they found that children prescribed antibiotics within the first year of life were 1.21 times more likely to be diagnosed with food allergy than children who hadn’t received an antibiotic prescription.

Higher antibiotic use = more allergies

The association between antibiotic prescription and development of food allergy was statistically significant, and the odds of a food allergy diagnosis increased with the number of antibiotic prescriptions a child received, growing from 1.31 times greater risk with three prescriptions to 1.43 times with four prescriptions and 1.64 times with five or more prescriptions.

The interdisciplinary research team, led by Bryan Love, Pharm.D., found that the strongest association was in children who were prescribed cephalosporin and sulfonamide antibiotics, which are broad-spectrum antibiotics, compared with narrower spectrum agents such as penicillins and macrolides. The study was published recently in the journal Allergy, Asthma & Clinical Immunology.

Healthy gut flora crucial

This research builds upon previous studies finding that normal gut flora is critical for developing the body’s tolerance to foreign proteins such as food.

Antibiotics are known to alter the composition of gut flora, and US children aged three months to three years are prescribed 2.2 antimicrobial prescriptions per year on average, according to the literature.

In the UK doctors are writing 10 million needless antibiotic prescriptions each year. Across Europe prescription rates for children under the age of 4 are higher than for any other age group.

The study’s results suggest a potential link between the rise in antibiotic prescriptions for young children and the rise in diagnosis of food allergies in children.

Given the study’s findings and the body of research suggesting that antibiotics are frequently improperly prescribed to treat viral infections, Love said that prescribing medical professionals should be cautious before ordering antibiotics for young children but noted that it can be difficult to distinguish between viral and bacterial infections.

“We need better diagnostic tools to help identify kids who truly need antibiotics,” he said. “Overusing antibiotics invites more opportunity for side effects, including the potential development of food allergies, and can encourage antibacterial resistance.”

• For more on this subject see also: New links between antibiotics, gut damage and modern disease

In the first research by charity Antibiotic Research UK, analysed 5 years of government data and  discovered that while the number of antibiotic prescriptions is coming down across England, GP practices in the most deprived parts of the country are prescribing 20% more and, worryingly, antibiotic prescriptions are on the increase in these deprived areas.

For instance, in Clacton-on-Sea, the UK’s most deprived area, we see antibiotic prescribing rates of almost twice the national average.

No reason for winter over-prescribing

The data also highlighted seasonal variation in prescription levels with 59% more prescriptions in December than in August with no obvious reason. Professor Colin Garner of Antibiotic Research UK says:

“It is true that colds and flus sometimes lead to bacterial infections due to suppressed immune systems and so we would expect a minor increase in antibiotic prescription in the winter months, however the data shows us a 59% jump in four months and this is far too high.”

One explanation is that patients are requesting antibiotics from their GPs for simple coughs and colds and GPs are irresponsibly acceding to these requests despite the advice they have been given not to prescribe antibiotics for viral conditions such as these.

The report suggests that an increased resistance by bacteria to antibiotics could change surgery as we know it today. As a consequence, new hips, knees, organ transplantation, open heart surgery and many cancer treatments will become even more high risk.

It is estimated that there are 400,000 cases of reported antibiotic resistant infections with 25,000 deaths each year in the European Union; in the UK the figure is close to 5,000 deaths per year.

And a new ‘superbug’ on the horizon

In a second and arguably more alarming study, Chinese and British scientists, writing Lancet Infectious Diseases, report that they have discovered a strain of Escherichia coli that is resistant to colistin, a ‘last resort’ antibiotic currently being used on strains of E. coli that are resistant to all other treatments.

Colistin is an older type of antibiotic that was rarely used for decades because there were other antibiotic options that have fewer side effects. As antibiotic resistance has increased, the drug has come back into more widespread use in both people and especially farm animals.

Experts argue that it should be preserved for people and should not be employed in agricultural operations, where vast quantities of antibiotics are fed to animals as growth promoters. And yet, in China, the drug is used more in animal production than it is on people.

Little surprise, then, that the researchers found the resistant bacteria in pigs, raw pork meat, and in a small number of people in China.

A portable mutation

This is not the first instance of colistin resistance in the scientific literature, but this study has revealed more about how that resistance works and it is this that has worried global health authorities.

The genetic mutation that makes the bacteria resistant is on a type of DNA (the MCR-1 gene) that is ‘portable’. In other words it is easily replicated and transferred – not just to other E. coli bacteria but to other types of bacteria as well.

British scientists and health experts described the discovery as ‘worrying,’ ‘disturbing’ and ‘alarming’ and there is a suggestion that this type of resistant bacteria may already be circulating in the UK in low numbers.

Spreading around the world

Professor Timothy Walsh, of Cardiff Institute of Infection & Immunity at Cardiff University, which took part in the study, said:

“The effect on human health posed by this new gene cannot be underestimated. The rapid spread of similar antibiotic-resistant genes suggests that all antibiotics will soon be futile in the face of previously treatable gram-negative bacterial infections such as E.coli and salmonella.

“Our investigations in China found that MCR-1 is already prevalent in E.coli samples found in live animals and meat products, and in a small number of human cases.

Walsh adds that MCR-1 is likely to spread to the rest of the world at an alarming rate unless we take a globally coordinated approach to combat it.

• See also our article Antibiotic alternatives – your 12-point plan

Natural Health News — The drugs we release into the environment are likely to have a significant impact on the growth of food crops, according to a new study.

By assessing the impacts of a range of non-steroidal anti-inflammatory drugs, the research published in the Journal of Ecotoxicology and Environmental Safety,has shown that the growth of edible crops can be affected by these chemicals – even at the very low concentrations found in the environment.

British researchers from University of Exeter Medical School and Plymouth University focused their analysis on lettuce and radish plants and tested the effects of several commonly prescribed drugs, including diclofenac and ibuprofen. These drugs are among the most common and widely used group of pharmaceuticals, with more than 30 million prescribed across the world every day.

The potential for these chemicals to influence plants is becoming increasingly relevant, particularly as waste management systems are unable to remove many compounds from our sewage. Drugs for human use make their way into soil through a number of routes, including the use of sewage sludge as fertiliser and waste water for irrigation.

This study looked for a number of changes in edible plants, assessing factors such as water content, root and shoot length, overall size and how effectively the plants photosynthesised.

Each drug was shown to affect the plants in very specific ways, with marked differences between drugs that are closely related. For example, drugs from the fenamic acid class affected the growth of radish roots, whilst ibuprofen had a significant influence on the early root development of lettuce plants.

Dr Clare Redshaw, one of the scientists leading the project at the Medical School’s European Centre for Environment & Human Health, said: “The huge amounts of pharmaceuticals we use ultimately end up in the environment, yet we know very little about their effects on flora and fauna. As populations age and generic medicines become readily available, pharmaceutical use will rise dramatically and it’s essential we take steps towards limiting environmental contamination. We haven’t considered the impact on human health in this study, but we need to improve our understanding quickly so that appropriate testing and controls can be put in place.”

There have been growing concerns about the presence of pharmaceuticals in the environment, particularly as evidence emerges of the effects they can have on the development of animals and antibiotic resistance in bacteria. Yet their ability to affect plant growth is poorly understood.

This study marks an important step in an emerging research field attempting to assess how very low concentrations of drugs can affect the growth of crucial crop plants. It specifically considered the non-steroidal anti-inflammatory drugs tolfenamic acid, meclofenamic acid, mefenamic acid, diclofenac, naproxen and ibuprofen.

The findings from a study published in the British Medical Journal show that this benefit is similar to giving statins to everyone over 50 years who is not already taking them.

The researchers from Oxford University and the British Heart Foundation conclude that the 150 year old public health message: “An apple a day keeps the doctor away” is able to match more widespread use of cholesterol-lowering drugs like statins, and is likely to have fewer side effects.

In the UK, lifestyle changes are the recommended first step to prevent heart disease. However, trial data suggest that statins can reduce the risk of vascular events, irrespective of a person’s underlying risk of cardiovascular disease. As such, calls are being made for greater use of statins at a population level, particularly for people aged 50 years and over.

Statins, however, are linked to a range of adverse effects such as muscle atrophy, liver damage and diabetes.

Statins versus apples

So the researchers set out to test how a 150 year old proverb might compare with the more widespread use of statins in the UK population. They analysed the effect on the most common causes of vascular mortality of prescribing either a statin a day to those not already taking one or an apple a day to everyone aged over 50 years in the UK.

The researchers assumed a 70% compliance rate (which is the percentage of people who are prescribed statins, and actually follow the prescription regimen) and that overall calorie intake remained constant.

They estimate that 5.2 million people are currently eligible for statin treatment in the UK and that 17.6 million people who are not currently taking statins would be offered them if they became recommended as a primary prevention measure for everyone over 50.

By their calculations, offering a daily statin to 17.6 million more adults would reduce the annual number of vascular deaths by 9,400, while offering a daily apple to 70% of the total UK population aged over 50 years (22 million people) would avert 8,500 vascular deaths.

However, side-effects from statins mean that prescribing statins to everyone over the age of 50 is predicted to lead to over a thousand extra cases of muscle disease (myopathy) and over ten thousand extra diagnoses of diabetes.

But a cowardly conclusion

In spite of the findings the authors refused to be drawn on the benefits of food over drugs. They write:

“This research adds weight to calls for the increased use of drugs for primary prevention of cardiovascular disease, as well as for persevering with policies aimed at improving the nutritional quality of UK diets,” they conclude.

However lead author Dr Adam Briggs of the British Heart Foundation Health Promotion Research Group at Oxford University said: “The Victorians had it about right when they came up with their brilliantly clear and simple public health advice: “An apple a day keeps the doctor away”. It just shows how effective small changes in diet can be, and that both drugs and healthier living can make a real difference in preventing heart disease and stroke.

While no-one currently prescribed statins should replace them for apples, we could all benefit from simply eating more fruit.”

• Follow this link to learn more about lowering cholesterol without statins.

A new report, by the group Action on Additives, shows that 52 children’s medicines surveyed contain at least one and sometimes two or three of the seven E-number ingredients known as the ‘Southampton Seven Additives’.

These ingredients are seven additives with proven links to hyperactivity in a scientific study carried out by Southampton University and commissioned by the Food Standards Agency (FSA) in 2007.

The 2007 study built on findings of a 2004 study, carried out by the same team at Southampton.

The 'Southamptom Seven' additives linked to hyperactivity

Food manufacturers have removed most of the colourings from hundreds of snacks, sweets and other products, after the FSA called for a voluntary ban in 2008.

They remain in children’s medicines however, even though in June this year, the European Food Standards Agency called for five of these colourings (all but Quinoline Yellow, E104) to be tested for genotoxicity – that is the ability of a substance to cause damage to DNA, the genetic material of our cells.

Key findings

The report names and shames several popular brands of children’s medicines and has revealed that:

• Four of the six colourings highlighted as causal by the researchers have been found in children’s medicines.
• The red colouring Carmoisine (E122) is used in five medicines, including Calpol Infant Suspension and Boots Paracetamol 3 Plus Months.
• The most frequently used colouring is Sunset Yellow (E110), in six medicines, including a treatment for epilepsy.
• Five medicines, including four antibiotics, contain Quinoline Yellow (E104).
• Five medicines contain Ponceau 4R (E124) including Anbesol Teething Gel.
• In total, research for the report found at least one of the six Southampton colourings in 19 children’s medicines.
• The preservative Sodium Benzoate (E211), was in 37 children’s medicines, including a Boots cough syrup, Tixylix, and six different Benylin cough mixtures or syrups.
• Four medicines formulated for children contained a colouring as well as the preservative sodium benzoate.

The manufacturers, including Boots and Johnson & Johnson, have stated that they felt that the additives are safe.

Click for larger image

Children’s medicines poorly regulated

However, medicines are subject to different, weaker regulations to food and drink.

Synthetic colourings are banned from food and drinks targeted specifically at children under 36 months under the EU ‘Weaning Directive’  because children’s developing physiology places them in a special risk group in relation to the ingestion of additives.

Yet, even medicines for children as young as 2 months contain colourings and preservatives that are banned from their food.

Action on Additives believes that the same protection offered to young children by the Food Standards Agency should also apply to medicines and is calling on the Medicines and Healthcare Products Regulatory Agency (MHRA) – the UK government body responsible for regulating all medicines – to remove them from children’s medicines

Parents need to be better informed

In July 2013, MHRA stated that it is committed to encouraging manufacturers to remove the colourings identified. But the Agency said it was unable to enforce a ban without further EU regulation.

In fact, the European Union issued its own guidance on the use of ‘colouring agents’ used in paediatric medicines, advising that special care is needed when formulating medicines for children. It highlights that the known risk of, for example, azo dyes, should be taken into consideration.

“We are concerned that some of our most trusted children’s medicines contain unnecessary colourings that have been linked to hyperactivity and attention deficit disorders,” says Lizzie Vann-Thrasher, Co-ordinator of Action on Additives. “Manufacturers of children’s medicines should follow the example of the food and drinks industry and remove these colourings from children’s medicines.”

To alert parents to the research, Action on Additives have published A Parent’s Guide to Additives in Children’s Medicines which is now available.

Action on Additives recommends that these additives should be banned and not simply ‘recommended for withdrawal’ or phased out in children’s medicines as they are in food and drink .

The group encourages parents and carers to learn more and to request additive free medicines. It is also important that parents report any adverse reactions to the Medicines and Healthcare Products Regulatory Agency (MHRA). This can be done online via the ‘Yellow Card’ scheme or pick up a leaflet at your local pharmacy.

While antibiotic ‘stewardship’ programmes have helped reduce some of the misuse of the the medications in hospitals, the analyses by Harvard University researchers,  published in JAMA Internal Medicine, suggests the message isn’t always getting through, with patients continuing to request antibiotics for conditions they don’t cure, and doctors prescribing them.

The inappropriate use of antibiotics adds to the creation of drug-resistant bacteria, or ‘superbugs’, which are very difficult to treat and are a public health threat.

“Also, people need to understand that by taking antibiotics for viral infections, they’re putting something in their bodies that they don’t need,” said Jeffrey A. Linder, MD, MPH, associate professor of medicine at Harvard Medical School, associate physician at Brigham & Women’s Hospital, Boston, and senior author of the study. “Taking antibiotics unnecessarily exposes people to adverse drug reactions, allergies, yeast infections and nausea, with no benefit.”

Antibiotics don’t work for viral infections

Sore throats caused by streptococcus bacteria (‘strep’) should be treated with antibiotics. But while people often think they have ‘strep’ throat, streptococcus is the cause only about 10% of the time. In most cases, a virus causes the sore throat. Acute bronchitis is almost always viral, and even when bacteria are involved, there is no need for antibiotics unless the patient develops pneumonia, said Dr. Linder.

To assess the antibiotic prescribing rate for sore throat, researchers determined there were 94 million visits to primary care physicians and emergency rooms for sore throats between 1997 and 2010, based on an extrapolation of 8,191 visits. Physicians prescribed antibiotics 60% of the time, a decrease from 73% from numbers reported by the same authors in 2001.

For acute bronchitis, researchers calculated there were 39 million visits to primary care physicians and emergency rooms between 1996 and 2010, based on a extrapolation of 3,667 actual visits. Researchers determined there was a significant increase in the number of visits for acute bronchitis to primary care doctors, from 1.1 million in 1996 to 3.4 million in 2010. They also noted an increase in the antibiotic prescribing rate in emergency rooms for this condition; from 69% to 73%, during the same 14-year period.

Time is the best treatment

Most sore throats and cases of acute bronchitis should be treated with rest, fluids and using a humidifer, and don’t require a visit to the doctor, said Dr. Linder. A cough, runny nose and hoarseness usually are signs that a sore throat is viral, not caused by strep. Pain relievers can help. Essentially a chest cold, acute bronchitis involves swelling and inflammation of the bronchial tubes in the lungs and typically follows a head cold or flu, which are viral infections. The illness lasts a week or two, but the cough, caused by lung irritation, may linger for weeks.

• See also our guide to soothing a sore throat naturally