Winning The Race Against Superbugs
About 700,000 people die each year from bacterial infections, according to the World Health Organization (WHO). In the US alone, 23,000 people die from drug-resistant infections, according to the Centers for Disease Control and Prevention (CDC). The world urgently needs new antibiotics, vaccines, diagnostics and other products to help fight the rise of drug resistant bacteria. If we fail to solve this problem, many advances of modern medicine that depend on fighting infection with antibiotics – routine surgery, cancer therapy, treatment of chronic diseases – may be jeopardized.
The global antibiotics pipeline is precariously thin
In December 2018, there were 42 antibiotics in the global clinical pipeline1, of which only 11 were being developed to treat superbugs on the WHO critical threat list.2
1 Pew Charitable Trusts, March, 2019
2 World Health Organization, “Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics”, 2017
Discovery of novel antibiotics to treat priority pathogens is not keeping pace with the rise in resistance
No approved classes of antibiotics have been discovered since 1962 for the most dangerous types of bacteria – Gram-negatives – and innovations to improve the diagnosis and prevention of drug-resistant infections have been slow. The science is challenging. The economic model that once meant we could rely on industry for a steady supply of new antibiotics simply no longer works. New economic models, like CARB-X, and increased investment are needed to drive innovation.
C. difficile, MRSA, Enterobacteriaceae (CRE), Neisseria gonorrhoeae, Acinetobacter – these are just a few of the deadliest superbugs targeted by projects in the CARB-X portfolio. The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) have published lists of urgent and priority drug-resistant bacteria. To be eligible for CARB-X funding, the research must target pathogens on the WHO and CDC lists.
Why Gram-negatives are so hard to treat
Bacteria have evolved ways to protect themselves against unwanted or toxic compounds such as antibiotics. Gram-negative bacteria have a double membrane or wall, along with a variety of defense mechanisms such as the ability to change their structure to avoid being targeted by the drug and efflux pumps that expel drugs out of the cell, making it difficult to design new antibiotics and effective treatments. Gram-positive bacteria by comparison have a single membrane barrier that is easier to penetrate to get the antibiotic into the cell. However, some Gram-positive bacteria like C. difficile are increasingly difficult to treat and can be deadly.
Antibacterial discovery is long, costly and uncertain
It takes on average 10 years and hundreds of millions of dollars to develop a new drug. Superbugs can develop resistance much faster and more efficiently. CARB-X focuses on projects in early development phases, often referred to as the “Valley of Death”, because it is in these early phases of research that many projects are abandoned because of lack of funding and support.
Where do antibiotics come from?
The first antibiotic was discovered in 1928 when researcher Alexander Fleming found a type of mold, Penicillium notatun, had halted the growth of Staphylococcus, bacteria that can cause skin infections and pneumonia, in his petri dish. It also was found to kill other bacteria. Many existing antibiotics are derived from natural sources like soil bacteria, but other therapeutic approaches are also showing promise. Building resistance to antibiotics is a natural defense mechanism in bacteria.