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Antibiotic Resistance: The Most Frightening Thing Since Ebola (August 2014)

 

We’ve all heard of the shocking outbreak of the Ebola virus in West Africa which has claimed the lives of over 1 500 victims to date. The most frightening thing is that we have no idea how to treat it. We may feel relatively safe from Ebola being separated by such a great distance. Yet this crisis forms a pertinent reminder that no matter how developed we consider Western medicine to be, we are still vulnerable to epidemic. Ebola isn’t a case of antibiotic resistance, but it shows us how scary the implications of resistance could be. Already around 25 000 people in Europe die each year from antibiotic resistant infections, according to the European Medicines Agency. There is every potential for this to get worse. Without effective antibiotics, patients will die from even the most simple of infections. Unfortunately finding a solution is not an easy task.

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The responsibility for addressing the problem of antibiotic resistance often seems confused. Who is accountable: prescribers, patients, pharmaceutical companies, governments? When I used to work on the dispensing counter in a pharmacy I dealt with a never-ending stream of customers filling prescriptions for antibiotics. I saw how they were often used irresponsibly. I also witnessed returning customers whose antibiotics were ineffective. Yet I have only had access to one part of the picture, so I set out to find out more about the state of antibiotic resistance and what is being done.

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I visit a local practitioner, Dr Jonathan Glover in his beautiful home in the countryside. He meets me at the gate with a broad smile and firm handshake. I sit down at his crowded table while he bustles about making me a tea. He leans back in his chair, coffee in hand, expectantly waiting for me to start. Dr Glover has a lot to say on the topic of antibiotic resistance. He sees its effects in his everyday work. He explains how common conditions such as urinary infections are having more and more samples showing multi- resistant strains of organism, which means that several types of antibiotics are ineffective. Dr Glover describes one particular type of these organisms, known as MRSA as “basically a plague of the hospital surgical team.” It can mean for example that hip-replacement patients can have to “go back to theatre, have their hip replacement taken out, packed with antibiotics and sometimes left for three months during which time they can’t walk.”

 

These cases of antibiotic resistance are increasing. More than half of all skin and soft tissue infections are now caused by MRSA, according to the Journal of Emergency Medicine. Dr Glover explains how when he first started practicing medicine in the 1990s “it used to be pretty much unheard of to get MRSA out in the community [rather than in hospital], but now we’re getting it pretty regularly.” Dr Glover also discusses another example of multi-resistant bacteria known as ESBL. ESBL can mean that those prone to illnesses such as urinary infections have to be given intravenous antibiotics as there are no oral alternatives that will work. “That’s a big red light for the health community to say ‘look this is an infection in the community and we just have nothing that we can treat it with’.”

 

The effects of antibiotic resistance aren’t always represented by hard statistics, but there certainly are frightening examples. A World Health Organisation report informs us that every year there are 440 000 new cases of multi-drug resistant tuberculosis resulting in at least 150 000 deaths. Antibiotic resistance is an issue that cannot be ignored.

 

One of the major explanations for why antibiotic resistance is such a chronic problem is the over-prescribing of antibiotics. I ask Dr Glover how often he prescribes antibiotics. He says he would be “upset” if he prescribed more than four or five on a typical morning of 15 patients. Even so, some of these would be delayed prescriptions, not to be used unless certain conditions arise. This surprises me considering the general trend of over-prescribing. However, I soon find that Dr Glover is a keen advocate of what the medical profession describe as “antibiotic guardianship,” which sees it as a prescriber’s duty to ensure antibiotics are used correctly.

 

I tell Dr Glover about how many customers I used to see in pharmacy using antibiotics for conditions such as colds and coughs. His grimace is obvious, “that’s painful to see and hear about.” Cold and flu symptoms are caused by viruses not bacterial infection, making antibiotic treatment utterly useless. Yet according to Harvard University researchers, doctors are still prescribing antibiotics for sore throats 60% of the time, despite the fact that sore throats are only caused by bacterial infection 10% of the time. Other symptoms such as coughs and runny noses are strong signs that the patient has a virus instead.

 

The issue does not lie solely with prescribers. One of the problems of clinical practice is that patients often come to a practitioner expecting a prescription. I have a chat with Mrs Brenda Birt, a recently retired prescribing nurse, while she keeps a watchful eye over her grandchildren. She has witnessed a lot of change within medical practice, but not within her patients’ views: “I don’t know how you get through to the broader community because they still feel if I’ve got a sore throat, I need penicillin, or I need so and so, and of course they don’t.”

 

The problem is not just that too many antibiotic prescriptions are being given out, but that patients are not finishing their courses. Dr Glover explained to me the importance of this. If a course of antibiotics is started but not finished then you have effectively “killed the weaklings and left the superbugs out and about ready.” This means that over many courses more resistant strains will reproduce and the infection will become unaffected by that particular drug.

 

I recently overheard a conversation where a woman said she was feeling “soooo bad” that she took her three day antibiotic course all in the one day and couldn’t believe that the doctor hadn’t prescribed her more. Antibiotics do not work like pain-killers, you can’t just take more at once if you feel worse. I was prescribed antibiotics recently and although I knew that I should complete my course at regular intervals, this information was not offered by the doctor. Dr Glover explains that under the concept of antibiotic guardianship, it is an important role of the prescriber to make sure the patient clearly understands their intentions.

 

My meeting with Isaac Batley, the Director of iS Health Group, a pharmaceutical consultancy company, gives me more to think about. Mr Batley ducks through the door of his local pub to tower above me. We find him a seat where he can stretch out his legs before the table. I quickly find out that he is perhaps Dr Glover’s worst nightmare. "You can educate the patient all day long saying this is the reason why you have to take the rest of your course… I know this, ok. I don’t finish all of my courses!” During a recent course, he had only taken three out of seven days when the issue cleared up. I joke that he shouldn’t admit that and make a play of covering my recorder. “But it’s true,” is his response, said with a shrug. Mr Batley is certainly the perfect reflection of a patient who knows all the right information, but ultimately doesn’t have the motivation to follow the rules exactly. “To be fair, he didn’t actually say to finish the course, he said to try not to start the course!” Even so, I think it’s fair to say that we can’t blame the doctor here! There is only so much a doctor can do.

 

Antibiotic resistance would be less concerning if there were new drugs stepping up to fill the role of antibiotics that are no longer functioning as they should. This sadly is not the case. There has been shockingly little antibiotic development in several decades. Mr Batley reflects on this, “I work with companies that do antibiotics, but at the moment no-one is really developing antibiotics.” If there is this obvious need for new antibiotics, why aren’t we seeing new drugs appearing on the pharmacy shelves?

 

“Antibiotics are not sexy!” Dr Glover proclaims, as an instant explanation to me. I suspect he has used this line before. He explains that if a pharmaceutical company were to develop an effective antibiotic at the moment prescribers would say “if it’s alright with you company, we will put this in our cupboard and we will never use it unless we really really have to and only then will we use it carefully.” At its base level, a pharmaceutical company is a business which will be driven by profit. Dr Glover sees the issue as a ‘market failure,’ where antibiotics aren’t being developed because they will not reap the same profits as drugs that will be used constantly for chronic conditions such as high blood pressure.

 

Mr Batley has quite a different idea. Mr Batley has worked with major drug companies such as Astra, Sanofi and Pfizer. As far as he is concerned the sole reason why pharmaceutical companies have not been producing antibiotic drugs is that the government has said they would not pay to have them used after their development. Mr Batley explains that there is a wide enough patient need that there would be a profit to be made even with the increased focus on responsible use. The problem is that governments “only have a finite budget to spend on drugs so a lot of their role is about reducing that spend and they have been saying for a long time that we don’t need antibiotics.”

 

It is difficult to credibly assess the extent to which this has impacted the development of antibiotic drugs. Yet this hypothesis does make sense in light of political trends. An example of this is the 1999 NHS reformation which set a strict cash-limited budget with increased ‘black-listing’ of drugs that were not considered ‘good value for money.’ Tony Blair, the Prime Minister at the time, saw this as the way to “harness new developments rather than be driven by them,” which really meant to choose which developments to accept and which to reject. Antibiotic resistance was not a major concern in the media at the time, so it is easy to see that antibiotic development could have been disadvantaged.

 

Nevertheless, the government is certainly now aware of the issue of antibiotic resistance. Prime Minister David Cameron has proclaimed that “if we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine where treatable infections will kill once again.” The government has started making plans. We can see this particularly with the UK Five Year Antimicrobial Strategy 2013-2018. However, there is a big jump between making plans and real progress being seen. Mr Batley at least, is yet to see any change reach the companies he deals with.

 

So what is the future of antibiotic resistance looking like? Responsible prescribing practice is perhaps a simpler issue to address. “I think we’re all getting a bit better,” Dr Glover muses. He explains that new systems are being put in place, such as scoring criteria for conditions that might justify antibiotics. There is still a long way to go. A 2014 survey undertaken by Medscape found that 12% of prescribers prescribed antibiotics without being certain they were necessary more than half of the time. A further 21% prescribed antibiotics 25 to 49% of the time without being certain. It is not reasonable to expect that antibiotics will never be given out without certainty, as sometimes medical situations require a ‘best guess,’ but it should still be better than this.

 

We cannot solely blame doctors for the overuse of antibiotics. The same Medscape survey found that 28% of antibiotics prescribed without certainty were given out because the patient requested a prescription. The most common reason for this was that the patient believed it would cure the illness, but another popular motivation was to be able to return to work quickly. It is no surprise that patients want to feel better quickly, of course they do. Dr Glover explains that he could refuse to prescribe an antibiotic, but there is nothing to stop that patient going elsewhere and amending their story to secure an antibiotic. It is important therefore that patients come to realise that it is in their long-term interests to make minimal use of antibiotics. “My job is not so much not prescribing the antibiotic, but educating the population… If I can explain to one patient why they haven’t got their prescription they may never come back for the same reason so that’s a big win.”

 

Nurse Birt has a fitting idea whilst watching her grandchildren play in front of her, “it needs to come through the schools. It needs to start from the bottom to go to the top.” She uses the example of smoking campaigns. Considering the widespread social effects of smoking education, I think she has a good point.

 

So we’ve established public awareness of antibiotic resistance is vital. Even so, no matter how responsible we are with antibiotic use to slow the problem down there still needs to be alternatives developed. To do so there needs to be co-operation between governments and pharmaceutical companies. However this is a more complicated issue than it may first appear.

 

Mr Batley explains the drawn-out process and many steps of drug development that takes 10 to 15 years “if you are going to start from scratch.” Considering this, Dr Glover is apt in assessing that “you’re stuck with a bigger problem if you haven’t got a solution ready for it.”

 

Some believe that governments need to directly pour funding into antibiotic development. This is beginning to happen with European governments partnering with private enterprise in programs such as COMBACTE under the Innovative Medicines Initiative. The program started from the beginning of 2013 and over 250 million euros has been assigned. This may sound like a lot of money, but we must keep in mind that each drug development costs millions to reach our pharmacies and hospitals.

 

Direct funding is not the only approach to the problem. Mr Batley argues that “I don’t think they [the government] should fund the development of drugs because it skews it [the market] and you take away the competition.” As far as Mr Batley is concerned what drug companies need is an assurance that by the time they finish developing their drug in 10 to 15 years, after investing millions, that there will be a place in the government’s budget for its use.

 

Mr Batley and I end up a bit off topic discussing the idea of ‘orphan drug status’, which means that in certain situations where there is nothing yet available to treat a minority condition, drug companies can be given an “easier and quicker route to getting their license and getting to market.” I can’t help but think that if the situation gets desperate enough a similar program will be needed for antibiotic development. We should hope not though. It is hardly desirable to decrease the safety barriers that drugs undergo before they meet our hospital shelves.

 

There is no single party responsible for addressing the issue of antibiotic resistance. David Cameron argues that he wants “to see stronger, more coherent global response, with nations, business and the world of science working together to up our game in the field of antibiotics.” It is all very well to say this, but practical change needs one step at a time. Dr Glover sums it up “there’s that old story that nobody did something that somebody was supposed to be responsible for, that anybody could have done.” Once we take a minute to absorb the riddle, it shows how we must all be an active part of the process or nothing will be done.

 

It is not too late to address the dilemma of antibiotic resistance. Yet public concern in the developed world at present is focused on other worthy causes such as cancer research. The Western public are yet to see the full extent of the danger of antibiotic resistance and the developing world are unable to fund it. Perhaps the tragic case of the Ebola virus will begin to open our eyes to see the disaster looming right before us.