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The Unmeasured Cost of Antimicrobial Resistance

Antimicrobial resistance could change modern medicine as we know it

With antimicrobial resistance becoming more of a recognised threat, in 2014 a review on the potential threat of antibiotic resistance was commissioned by the then Prime Minister of the UK. Economist Jim O’Neill was tasked with quantifying the threat of antimicrobial resistance in terms of human lives.

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The review estimated that by the year 2050, if we dont act to curb the growing threat of antimicrobial resistance, 10 million deaths will occur as a direct consequence of antimicrobial resistance. This figure has since been quoted a lot, to really drive home the magnitude of the threat. However, this estimate isn’t a true measure of the cost of antimicrobial resistance, because it only quantifies anticipated deaths due to infections through resistance mechanisms we know about.

It doesn’t take into account the fact that antimicrobials have become an integral part of modern medicine.

This figure excludes resistance due to new mechanisms, which continue to show up as we build larger collections of microbes and search their genomes for features that explain the resistance of organisms to drugs we rely on. It also excludes deaths due to a change in the calculus that medical professionals and patients need to make when deciding whether to perform life-saving medical procedures.

Antibiotics have shaped modern medicine

Humans have always been plagued by infections. However in the 1940s, following the discovery of penicillin, it seemed we had finally freed ourselves from the scourge of bacterial infections (exemplified by the US surgeon general famously announcing in 1968 that “the war against diseases has been won”).

Modern healthcare has been built up over the past century on the basis that infections can be prevented or treated using antimicrobials. Surgical procedures have undergone stunning transformations in terms of their safety. Before the discovery of antibiotics, going under the knife frequently resulted in the loss of patient life. In the very early days of surgery, before anaesthetics, surgeons’ skill was measured largely by their speed. Patients would need to be held down, and surgeons needed to work as quickly as they could, against the patient’s struggling, to complete their task. The introduction of anaesthetics allowed for longer, more technical surgeries, but unfortunately led to wounds being open for longer and surgeons hands and tools (both unwashed) lingering in these wounds longer. As a result, mortality rates in hospitals actually rose during the 1800s.

For a long time, the greatest risk in surgery wasn’t something going wrong during the procedure, it was infection following it. Many surgeries we take for granted today, particularly operations on the torso, would rarely be considered before antibiotics, because of the near certainty they could result in deadly infection. The introduction of antiseptics, and later antibiotics prior to surgery to prevent infection (called prophylactic antibiotics) dramatically changed the types of surgeries that could be performed without an intolerable risk to the patient’s life.

“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” — David Cameron, former UK Prime Minister

Antimicrobial resistance is said to present a risk that we will fall back into the pre-antibiotic era. However, this is misleading. Our health system is now designed to treat more chronic conditions. Healthcare has become progressively more technological and invasive, and antimicrobials have become an integral part of providing this type of care. For example, antimicrobials are given as standard to prevent infection during surgery, to women delivering by caesarean section, and to cancer patients undergoing chemotherapy. Antimicrobials have become pivotal in extending the overall health of human societies. Resistance doesn’t just impact infectious disease directly; it affects the surgeries we perform, our ability to treat cancers, and our health system as a whole.

Medicine today

Almost 50 million surgeries are performed in the US every year. Rates of infection following surgery are around 11% without antibiotics and 4% with antibiotics. The baseline risk of infection following surgery varies depending on the procedure, from 3% for surgery on a hip fracture to 40% for colorectal surgery. These days, patients will often be given antibiotics around 2 hours before major surgery, to make sure that the life-saving drug is in the bloodstream during surgery, ready to kill bacteria as they appear. Antibiotics reduce the risk of infection by varying amounts, from 35% for cancer chemotherapy to 86% for having a pacemaker implanted. For every 75 colorectal surgeries performed, prior antibiotic treatment can prevent 20 infections and one death.

The source of antibiotic resistant infections is two-fold. There is strong selective pressure for bacteria circulating in hospitals to become resistant to antibiotics. In addition, we can carry antibiotic resistance into the hospital with us when we arrive. One example is the bacteria MRSA — before many surgeries patients must come in two weeks before the procedure to be swabbed and tested to see if they carry the bacteria. If they do, they need to be treated to eliminate this bacteria before it’s safe to operate. Many of us carry MRSA and it causes us no harm — it’s not until we go under the knife that the bacteria have an opportunity to cause a threatening infection.

In the USA, about 650,000 cancer patients receive chemotherapy each year. This life-saving treatment wipes out the patient’s immune system, making them extremely vulnerable to infections. Currently, about 10% of these patients develop an infection that requires a visit to the hospital. Our ability to treat these infections is critical to saving or extending the lives of cancer patients.

“It is quite possible — and perhaps even likely — that the recent era of material mortality improvements will give way to many years of material mortality worsening” — Sally Davies, UK Chief Medical Officer

A recent study in the Lancet estimated that 40–50% of bacteria that cause surgical site infections, and a quarter of bacteria causing infections after chemotherapy are resistant to standard antibiotics used to prevent infections due to these procedures in the USA. The study found that our current prophylactic procedures are already unreliable in preventing infections by common pathogens, which commonly show up in hospitals with resistance to the drugs we use. But the situation is likely to get worse in the future. The authors of the study predicted that a 30% reduction in the effectiveness of these antibiotics would result in an extra 120,000 infections and 6,300 more deaths following the 10 most common surgical procedures each year.

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Resistance to prophylactic drugs are one thing, but what’s really worrying are the infections that can’t be treated by any antibiotics. A 2009–10 survey found that a lot of the bacteria that are associated with surgical wound infections are resistant to our last-line antibiotics, that we use for drug resistant infections. This means that not only would routine surgeries result in infections, which cause more patient suffering and cost more money and time to treat, but that the patient may not survive their infection.

How will we deal with this?

Failing major improvements in how we manage antibiotics, choices around whether or not to perform surgeries will become more difficult. For a life-or-death surgery, this will likely go ahead regardless, with an understanding that the patient’s chances of surviving aren’t as good. Elective procedures like joint replacements will become a tougher decision. The first hip replacement came in 1947. As of 2015, 332,000 Americans a year now undergo that operation. Joint replacements offer relief of pain, better quality of life, and more mobility, which can improve lifespan. However, if a joint replacement becomes too much of an infection risk, its likely to be avoided altogether, leaving the patient to cope with the worn joint instead.

One (temporary) solution to this problem could be to change the antibiotics that are given to patients before surgery, to ones that fewer bacteria are resistant to. This would be a very risky strategy long-term, though, because it would change the selection pressures in hospitals to favour bacteria that are resistant to the new drugs. Over time this would limit our options for treating infections even more. An alternative would be to take a personalised approach, where each individual is screened for antibiotic resistant pathogens before surgery. In theory this would prevent the patient’s own bacteria from infecting them, but it assumes that the initial screen is thorough enough to capture any bacteria living on the patient that could potentially cause infection. It also doesn’t account for bacteria present in the hospital environment or carried by the surgical team, other patients, or visitors.

The major solution being put forward is antimicrobial stewardship. Antimicrobial stewardship involves interventions aimed at creating systemic change in how we use antibiotics. These interventions include making sure physicians are prescribing the right drug for a given infection, saving some antibiotics as “drugs of last resort” that are only used for multi-drug resistant infections when absolutely necessary, and making sure hospitals do everything they can to prevent infections from occurring in the first place.

However, attempts to improve antimicrobial stewardship have often been met with scepticism, manipulation, or even hostility by clinicians. A major impediment to implementing change is pressure, particularly from parents of patients. Clinicians have admitted to “caving” to pressure from parents when they’re concerned about their child’s health and want every step to be taken to make sure they’re getting the best treatment. Improved awareness of the growing threat of antimicrobial resistance, and the impact that different interventions can have are required to make sure that people act on recommendations.

Further reading

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To see more about what we do, visit our website; to learn more about what we’re doing to track the global spread of antibiotic resistance, see the Global Health Research Unit.

Bioinformatician + data scientist, building machine learning algorithms for the detection of emerging infectious threats to human health

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