Robotics, Security & Safety: The Rise of Antibiotic Resistance
On 28th September 1928 a piece of mold fortuitously contaminated a petri dish in Alexander Fleming’s laboratory at St Mary’s Hospital in London.
He discovered that it produced a substance that killed the bacteria he was examining. After months of calling it "mold juice", he named the substance penicillin (from Latin penicillus, “paintbrush,” in reference to the shape of the mold cell structures).
If you use penicillin, use enough.
Sir Alexander Fleming, Nobel Laureate1
Over the following decades penicillin became the “wonder-drug,” curing millions of patients suffering from bacterial infections. Other compounds with anti-bacterial, or “anti-biotic”, properties were later discovered and revolutionized healthcare, forming the bedrock of many of the greatest medical advances of the last century. Many infectious diseases, such as pneumonia and tuberculosis, which had often proved fatal, could now be treated effectively. Together with Howard Florey and Ernst Boris Chain, Alexander Fleming received the Nobel Prize in Physiology or Medicine for their work in the field of antibiotics in 1945.
There is no doubt that penicillin and other antibiotics are amongst the greatest inventions in the field of medical science. Yet Fleming's warning has always haunted their success. Antibiotic resistance is today a costly and dangerous problem. Some people fear there may be worse to come: a strain of resistant bacteria for which no treatment is currently available might start an epidemic. In such a scenario, elective surgeries, such as a hip replacement, bariatric surgery or colectomy, may come to be seen as unacceptably risky. Non-elective surgeries would also become more dangerous and the risks of procedures which suppress the immune system, such as organ transplants and cancer chemotherapies, would increase.
What are the consequences of antibiotic resistance?
Antibiotic resistance is the ability of a microbe to resist the effects of medication previously used to treat them. Resistance arises in one of three ways: (1) natural resistance in certain types of bacteria, (2) genetic mutation, or (3) one species acquiring resistance from another. Resistance can appear spontaneously (e.g. random mutations), but more commonly builds up gradually over time, and this may be caused by misuse of antibiotics.
According to the Center for Disease Control and Prevention, at least 2 million people in the US become infected with bacteria resistant to antibiotics every year, and at least 23,000 people die as a direct result of these infections.2 Already the cost to the US healthcare system of dealing with infections resistant to one or more antibiotics is USD 20 billion a year.3 Worldwide the annual mortality rate from antibiotic resistance is more than 700,000 people and by 2050 this number could rise to 10 million.4 Without global action, the implied economic cost of drug-resistant infections would be at least USD 100 trillion and could cut the annual world’s GDP by 2 - 3.5% by 2050. These figures almost certainly underestimate the actual costs, because they are based on the direct costs of disease and on deaths caused by the most important drug-resistant pathogens, but the additional secondary health effects could be just as large.5
Antibiotic resistance is often a direct result of rising antibiotic use. The greater the volume of antibiotics used, the greater the chances that super antibiotic-resistant population of bacteria will prevail in a “survival of the fittest” contest between the bacteria. Two trends are contributing to a global rise in antibiotic consumption:6
- Rising affluence as well as expanding insurance coverage increases the access to antibiotics. On one hand this saves lives, but on the other, the increasing usage also drives up resistance.
- Increased demand for animal protein and resulting intensification of animal production for food is leading to a greater use of antibiotics in agriculture. This increase in usage also drives up antibiotic resistance.
Trends in antibiotic use
Between 2000 and 2010 total antibiotic consumption grew by more than 30%, from approximately 50 billion to 70 billion standard units (SU).7 Penicillin and cephalosporins accounted for nearly 60% of total consumption in 2010, an increase of 41% from 2000. The countries consuming the most antibiotics overall in 2010 were India (13 billion SU), China (10 billion SU) and the United States (7 billion SU). The consumption shown on a “per capita” basis demonstrates: The United States led with 22 units per person (2010), compared with 11 units in India and 7 units in China. Per capita consumption is generally higher in higher income countries, but the greatest increase in the use of antibiotics between 2000 and 2010 was from the Emerging Markets, and consumption continues to rise.
In most countries, about 20% of antibiotics are used in hospitals and other healthcare facilities. 80% are used in the community, either prescribed by healthcare providers or purchased directly by consumers without prescription. Perhaps half of all use is inappropriate and avoidable. The use against mild coughs and the common cold is typically ineffective, but it adds to the growing global resistance to antibiotics.8
The Centre for Disease Dynamics, Economics & Policy (CDDEP), a think-tank, developed a drug resistance index. The index aggregates information about antibiotic resistance and antibiotic use into a single composite measure that quantifies the decay of antibiotic effectiveness over time. The index runs from zero, meaning that antibiotics are fully effective, to 100, which means pathogens are fully resistant. In 27, mostly European, countries CDDEP calculated the index between the years 2000 and 2014. It shows that the effectiveness of antibiotics has declined in 22 of these 27 countries. Only Germany and Sweden actually buck the trend and improve. In India, the poorest country in the group, the index suggests that antibiotics used to treat most bacterial infections now fail to work.
The prevalence of sepsis is another indication that global antibiotic resistance is on the rise. The number of cases of sepsis rose from 621,000 to 1,141,000 between the years 2000 and 2008, and number of patients who died from sepsis also rose from 154,000 to 207,000. One reason for this is the emergence of “MRSA” (methicillin-resistant staphylococcus aureus), a bacteria which is no longer susceptible to methicillin (a descendent of penicillin).9
What can be done against antibiotic resistance?
To stop the global rise of drug-resistant infections, there is a supply and demand problem that needs to be solved. According to the Review of Antimicrobial Resistance, the following steps should be taken (summarized):10
- Reduce unnecessary use of antimicrobials in agriculture: There are circumstances where antibiotics are required in agriculture and aquaculture, such as to maintain animal welfare as well as food security. However, much of their global use is not for treating sick animals, but rather to prevent infections or simply to promote growth.
- Improve global surveillance of drug resistance and antimicrobial consumption in humans and animals: Surveillance is one of the cornerstones of infectious disease management, which has been until recently often ignored.
- Promote new, rapid diagnostic instruments to cut unnecessary use of antibiotics: Rapid diagnostics could transform the way we use antimicrobials in humans and animals. Reducing unnecessary use of antibiotics could slow the development of its resistance.
- Promote the development of vaccines: Vaccines can prevent infections and therefore lower the demand for therapeutic treatments, reducing use of antimicrobials and therefore slowing the rise of drug resistance.
- Better incentives to promote investment for new antibiotic drugs: Currently the commercial return for developing antibiotics looks unattractive: The total market for antibiotics is about USD 40 billion of sales per annum. But only around USD 4.7 billion of this amount is from sales of patented antibiotics (that is about the same number the as yearly sales for one top-selling cancer drug). So it is not surprising that companies are not investing in antibiotics despite the very high medical needs. New commercial models are needed to encourage innovation.
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