Clinicians have relied on antibiotics to treat bacterial infections ever since they were discovered in the early 20th century. As a result, mortality and hospitalization rates that resulted from common infections went down. So did the Western world’s urgency to pursue alternative methods of fighting bacteria.
Since the discovery of antibiotics, western researchers have instead focused on developing drugs that block an essential enzyme or process that bacteria require to survive or replicate. At first, this approach was successful. Several new classes of antibiotics were discovered and brought to market. However, the antibiotics developed in recent years have been second, third, fourth or even fifth generation versions of the products discovered decades earlier. Researchers have tried exhaustively to find new drugs or drug targets through genomic approaches, bioinformatics, and high throughput screening with little success.
Unfortunately, this approach has created a situation where the last novel class of antibiotics to be approved was discovered in 1987. Moreover, the last novel class of antibiotic capable of treating Gram negative infections was introduced in the 1960s. Gram-negative bacteria have a more complex cell wall, containing two cellular membranes, which provides protection to the bacteria and makes it difficult for some antibiotics to access and interrupt their intracellular machinery. In the meantime, bacteria rapidly developed resistance to the antibiotics in use while the novelty of the drugs used to fight them stagnated. Today, the Centers for Disease Control and Prevention estimates that drug-resistant infections kill approximately 23,000 people per year in the U.S. at a cost of more than $20 billion to our healthcare system.
To address this public health crisis, innovative methods must be explored to treat and prevent infection. The White House stressed the importance of novel thinking in this area by including in the National Strategy for Combating Antibiotic-Resistant Bacteria (CARB) the goal of developing “non-traditional therapeutics and innovative strategies to minimize outbreaks caused by resistant bacteria in human and animal populations.”
Some therapeutics that were no longer pursued after antibiotics became widely used might prove worthy of additional research. Take bacteriophage therapy, for example. Bacteriophages are viruses that specifically infect bacteria. Discovered in 1915, bacteriophage research and clinical trials spread quickly throughout Europe and the United States in the 1920s and 30s. By the 1940s, companies such as Eli Lilly had begun to commercialize bacteriophage treatments, and World War II Russian soldiers carried bacteriophage treatment doses for dysentery. However, starting in the 1950s, interest in bacteriophage therapies within the United States and the western nations waned as multiple antibiotics were discovered and commercialized. Drug manufacturers saw the promise of small molecule antibiotics, which could act in a broad spectrum manner against a range of bacteria, as a potent and efficient means treating diseases.
Other examples of nontraditional therapeutics being researched include, but are not limited to, antibody therapies, altering or supplementing the bacteria that naturally populate the human intestine, or harnessing the power of the human immune system to fight infection. BARDA is not yet funding any nontraditional therapies in the antibacterials portfolio, but is considering future investments in this area.
In September 2015, BARDA entered into a cooperative agreement with the UPMC Center for Health Security Inc. The first objective of this program is to gain a better understanding of the scientific, regulatory, clinical, and commercial challenges that must be overcome in order to advance nontraditional antimicrobial therapy development. UPMC will conduct literature searches, interviews, and a workshop of invited attendees before delivering a final detailed report. This assessment will help inform BARDA’s strategic direction as the organization considers future investments in these types of therapies for resistant bacterial infections as well as emerging infectious diseases.
As researchers pursue new and more effective antibiotic therapies, it is up to all of us to protect the antibiotics that we have by ensuring that we use them appropriately. The use of antibiotics is the single most important factor leading to antibiotic resistance around the world. Whether you are a potential patient, medical professional, or an agricultural professional, you have an important role to play in protecting existing antibiotics. Take some time during Get Smart about Antibiotics Week to learn about actions that you can take to help protect the antibiotics that we all rely on to stay healthy.
