08 June 2016 14:25:47

Antibiotic Armageddon

Antibiotics have been one of the major advances in medicine over the last century and have (with vaccination) led to the near eradication of diseases such as tuberculosis in the developed world. Unfortunately, their effectiveness and easy access has led to overuse, especially in livestock raising, prompting bacteria to develop resistance.

In 1928, Alexander Fleming identified penicillin, the first chemical compound with antibiotic properties. Fleming was working on a culture of disease-causing bacteria when he noticed the spores of green mould in one of his culture plates. He observed that the presence of the mould killed or prevented the growth of the bacteria.

The World Health Organization has classified antimicrobial resistance as a "serious threat [that] is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country"

According to Dame Sally Davies, 50,000 people are dying every year in Europe and the USA from infections that antibiotics have lost the power to treat. She has described the threatened loss of antibiotics to the world as on a par with terrorism and climate change.

From tuberculosis to gonorrhoea, infections that used to be easily treated have once again become a serious threat. The Sexually Transmitted Bacteria Reference Unit (STBRU) at Public Health England (PHE) has recently detected an outbreak of high-level azithromycin-resistant gonorrhoea in northern England. The outbreak was first detected in Leeds in March 2015 and now appears to have spread to neighbouring areas in the north of England. Eleven cases have been reported in the Leeds outbreak, and since then a further four cases have been detected in patients from Macclesfield, Oldham and Scunthorpe. Some of the cases have reported partners from other parts of England. All cases to date have been in heterosexual patients. An outbreak control team meeting has been convened and STBRU is currently performing next-generation sequencing on these strains to better understand the molecular epidemiology.

There are an estimated 480,000 cases a year of multidrug-resistant (MDR TB) and 190,000 deaths from it. MDR TB is hard to treat, requiring two years of antibiotics that are not available or affordable in some poorer countries. The World Health Organization has just recommended a new shorter regime, lasting nine to 12 months, but cases of extremely drug-resistant disease - XDR-TB - have emerged and are often lethal.

The golden era of antibiotics, when new ones were often being discovered, is long past. It has become increasingly difficult for pharmaceutical companies to develop new ones as the old ones have lost their power to cure through overuse. Bacteria become drug-resistant by evolving to overcome antibiotics. That means new drugs must be used as little as possible, to keep them for extreme circumstances where the older drugs fail.

So the old model, in which pharmaceutical companies develop a new drug and then market it to sell as much as possible, is not in anybody's interest, because the more these drugs are used the faster they lose their potency.

Among Lord O'Neill's recent proposals is a new way of repaying companies for their inventions, through a "market entry reward" - a payment of around $1.3bn (£890m) to the successful developer of a new antibiotic for an "unmet need".

This, for the first time, would cut the link between research and development and the price of a drug, which is a model that campaigners have advocated for other diseases where the price of drugs is unaffordably high.

A blueprint to end the scourge of antimicrobial resistance proposes that drug companies should foot the bill for the development of new antibiotics and that patients should not be able to get them without a test to ensure they are needed.

Economist Jim O'Neill, who was charged two years ago by David Cameron with finding answers to one of the most pressing problems in the world today, says the global financial cost of no action would be the loss of 10 million lives a year by 2050 and £69tn ($100tn) a year.

"One million people have died while we have been doing this review," said Lord O'Neill, who became a minister while completing the report. Without action, he said, there would be more people dying in the future than are dying of cancer. The two most eye-catching proposals advanced by O'Neill are: to force the pharmaceutical industry to "pay or play" and to ban doctors from prescribing antibiotics until they have carried out rapid tests to prove the infection is bacterial. "We must stop treating antibiotics like sweets, which is what we are doing around the world today," he said. However, there must be incentives to develop such tests which do not yet exist. Doctors and policymakers need to get out of their comfort-zone, he added. "By 2020 it should become mandatory to use rapid diagnostics before antibiotics are prescribed."

In a report on near patient testing from June 2015, several studies show that by resolving diagnostic uncertainty, c-reactive protein Point of Care Test (CRP POCT) can reduce antibiotic prescribing for RTIs in primary care by up to 42% (in suspected lower RTIs with a cough lasting less than four weeks together with one focal and one systemic symptom), without a clinically significant increase in complications or missed diagnoses. CRP POCT is cost-effective, does not markedly increase workflow in most practices and had no effect on the rate of RTI consultations during long-term follow-up. Indeed, giving patients evidence-based information improves their satisfaction with the consultation and could lead to fewer visits through improving patient education in self-management.

That would be an incentive for industry to invent the rapid diagnostic tests needed and a new Global Innovation Fund worth $2bn over five years would help pay for this and other research. Low-income and middle-income countries should be subsidised to buy the tests. Recent headlines revealed that the total number of antibiotic prescriptions dropped by 7.3% from 2014/15 to 2015/16, compared to a target of 1%, while use of broad-spectrum antibiotics fell by 16%, compared to a target of 10%. This suggests UK GPs are at least making an effort to reduce their prescribing.

However, there must also be urgent action to stop the use of highly critical antibiotics in animals, which are the last line against infection in humans, said the report. Recently bugs resistant to colistin, one of the antibiotics of last resort, were found in China, where the drug has been used in farm animals.

""In some parts of the world, probably in the largest emerging economies and almost definitely in the United States, the use of antibiotics in animals is greater than in humans and that means the misuse is probably higher too," said O'Neill. A change in consumer habits might help. O'Neill said: "An emerging generation is becoming more choosy about what they eat." Products should be labelled so consumers could see where antibiotics have been used, he added.

If you are trying to reduce antibiotic prescribing, we have patient leaflets for you to give to your patients that explain the decision.