President Obama’s recent executive order on antibiotic resistance has called attention to a growing problem that is threatening to undermine the extraordinary achievements of modern medicine. The President’s executive order and the accompanying “National Strategy for Combating Antibiotic-Resistant Bacteria” call for a broad range of measures to conserve the antibiotics we have and to develop new ones.
To better understand why these measures are so important, it helps to understand the concept of “selective pressure.” Selective pressure is a force that causes an organism to evolve in a certain direction. When organisms reproduce, random mutations (biological changes) occur that sometimes confer an evolutionary advantage. In the case of antibiotic resistance, the bacteria that are not killed by antibiotics pass along the antibiotic-resistant trait to their offspring. As the offspring reproduce, the antibiotic-resistant trait becomes more common because the bacteria without it are killed off. Eventually, the entire bacteria population becomes resistant, resulting in life-threatening antibiotic-resistant infections such as MRSA, VRE and CRE.
Because bacteria grow more quickly and in larger numbers than other organisms, the effects of selective pressure can show up very rapidly in hospital settings where the frequent and sustained use of antibiotics results in consistent selective pressure on bacterial populations. As a result, hospital-acquired infections (HAIs) have become a huge issue, claiming more than 20,000 lives annually in the United States alone. The total cost of antibiotic resistance to the U.S. economy has been estimated at a staggering $35 billion, including $20 billion in direct healthcare costs, according the Centers for Disease Control.
With the Rise of AI, What IP Disputes in Healthcare Are Likely to Emerge?
Munck Wilson Mandala Partner Greg Howison shared his perspective on some of the legal ramifications around AI, IP, connected devices and the data they generate, in response to emailed questions.
Eliminate selective pressure and eliminate antibiotic resistance
The good news is that evolutionary theory also offers a means of discouraging the emergence of antibiotic resistance – namely, the reduction or elimination of the selective pressure. For instance, a short-term, high dosage regimen of antibiotics is usually preferable to a long-term, mild dose because it is less likely to leave bacterial survivors that can pass along the antibiotic-resistant trait to their offspring. Similarly, an incomplete drug regimen can allow bacteria to survive and adapt, so it’s important to take the full complement of pills that has been prescribed.
Yet another strategy to fight antibiotic resistance is to develop anti-infective therapies that defy the biological pathways bacteria use to become resistant. One way bacteria acquire drug-resistant characteristics is through mutations that create changes in the proteins of their outer cell membranes, thus preventing antibiotics from locking onto their cell membrane receptors. As a result of these mutations, bacterial receptors become resistant to antibiotics. My company, Ruthigen, is developing a non-antibiotic, anti-infective agent called RUT58-60 that has been shown to compromise bacterial cell membrane integrity and kill bacteria within 30 seconds of contact time.
Most importantly, unlike with antibiotics, these bacterial changes are not reversible.
A Personalized Approach to Medication Nonadherence
At the Abarca Forward conference earlier this year, George Van Antwerp, managing director at Deloitte, discussed how social determinants of health and a personalized member experience can improve medication adherence and health outcomes.
RUT58-60 is designed for prophylactic use in abdominal surgeries to prevent infection. Abdominal surgery represents about 34 percent of all post-surgical infections. By helping to reduce the incidence of post-surgical infections, RUT58-60 may eventually reduce the need for follow-up treatment with antibiotics, which in turn – as we have seen – decreases selective pressure, thus discouraging the emergence of antibiotic resistance.
Because of selective pressure, the average time to resistance of new antibiotics has decreased dramatically. From the 1940s to the 1980s, the average time to resistance for a new antibiotic exceeded 10 years; today, it is approximately a year, which is largely due to the fact that new antibiotics are basically new versions of existing antibiotics to which bacteria have already developed resistances.
Rather than struggling to stay a step ahead of bacteria’s skillful ability to adapt and survive, science and industry must work together to develop new approaches to fight harmful bacteria that elude Mother Nature’s wily defenses.
