It is impossible to overstate the importance of antibiotics to global and individual health. Antibiotics have saved the lives of millions of people, and almost everyone will have taken a course of the drugs at some point.
The misuse of antibiotics has meant their effectiveness has waned while the number of deaths due to infection has risen. The answer? Minimise the use of existing antibiotics through appropriate prescribing and greater use of vaccines, develop effective new medicines and find new ways to incentivise companies to invest in antibiotics research and development, while discouraging their unnecessary use.
Alexander Fleming discovered penicillin mould in 1928. The mould was developed into an antibiotic medicine during the 1930s and was first used during the second world war. By D-day, 6 June 1944, there was enough penicillin to treat bacterial infections experienced by the troops. During the 1940s and 1950s, additional antibiotics, such as streptomycin, tetracycline and vancomycin, were discovered.
Antibiotics completely transformed people’s lives. David Payne, head of GSK’s antibacterial discovery performance unit, says: “In the pre-antibiotic era, many people died from minor infections. It’s very rare that someone will die from an infected cut these days. The use of antibiotics has increased life expectancy substantially; you may only take them for one or two weeks, but they cure you from that infection and can extend your life expectancy maybe by decades.”
However, over the past 25 years, the bacteria M. tuberculosis, S. aureus and E. coli, among many others, have begun to show a resistance to antibiotics, a situation that threatens global public health. “There are documented cases where people have infections caused by bacteria that are resistant to all the available antibiotics, and the mortality in those patients is very high,” Payne says.
According to the 2014 Review on Antimicrobial Resistance, chaired by Jim O’Neill, former Goldman Sachs chief economist and UK government Treasury minister, if antibiotic resistance is allowed to increase at its current rate, it is projected to cause up to 10 million deaths a year globally by 2050.
Some of the factors behind this resistance are well-known, such as the overuse and inappropriate use of antibiotics for illnesses that they can’t treat, such as viral infections.
Even in 1945, when he was awarded the Nobel prize for medicine, Fleming was aware of the possibility of bacterial resistance. Some bacteria genetically mutate to become resistant to antibiotics; others may acquire resistance via contact with another.
According to the 2016 report by the Review of Antimicrobial Resistance, also chaired by O’Neill, there are now an estimated 700,000 deaths worldwide from drug-resistant infections. About 50,000 of them are in Europe and the US.
A Perfect Storm?
So why not just find another drug? Few new antibiotics have been approved for use in decades and we now face a perfect storm – as resistance increases, the availability of innovative antibacterials decreases. There is no one cause of this, but there are two major challenges, scientific and commercial. First, the complex structure of many bacteria means that developing new medicines capable of penetrating and killing them is exceptionally difficult, and failure rates are higher in antibiotics research and development than in most other areas.
Second, the commercial model used by pharmaceutical companies involves generating a financial return on investment, which goes up as the use of the medicine increases. The more a medicine is prescribed, the more patients it helps and the greater the return on investment. This works well for most medicines, but not for antibiotics: new antibiotics should be used sparingly and kept in reserve to avoid resistance, which makes it difficult for companies to recoup their investment.
It is crucial, however, that these drugs are available when they are needed. The new proposed industry model does not rely on the number of prescriptions being sold. GSK and others, for example, G20 health ministers, advocate a “de-linked model”, which separates return on investment from the number of prescriptions being sold. The proposed model will act as an incentive to invest in antibiotic research and development, and remove any pressure to generate sales through increasing the use of the new medicine.
Other areas of GSK’s work ensure that the need for antibiotics is minimised in the first place. GSK is a world leader in supplying vaccines aimed at preventing both bacterial and viral infections, which can thereby result in reduced use of antibiotics. As a leading supplier of antibiotics, GSK also provides antibiotic surveillance across 42 countries and 70 centres, gathering country-specific resistance data which is then shared with public health stakeholders and healthcare professionals to support appropriate prescribing.
Payne stresses the potential impact of neglecting antibiotic resistance: “There will be an increasing number of people with infections where we will run out of options to treat them. This will not only have a huge impact on the individual patient, but will also stop medical advances. We can only do complex life-changing surgeries if we can protect that patient from bacterial infections during the surgery.”
Payne is positive about how public/private partnerships are playing such an important part in maintaining antibiotic research, but considers it is critical to take the next step: “We need to apply this new commercial model to a specific antibiotic and test this approach within a pilot to see if it is feasible. We are very open to applying this to one of our antibiotics in development.”
by Sue George
