As last-resort antibiotics and antivirals continue to lose their effectiveness against once easily treated infections, the urgency to find effective medications has become a priority of the World Health Organization (WHO) and national health agencies worldwide. While research into new antimicrobials can produce successful novel therapies, the process of getting a new drug to market is too slow to keep ahead of ever-evolving superbugs. To address this challenge, innovative organizations are rediscovering antibiotics of the past, and with the help of modern techniques and technology, are developing new weapons in the war on antimicrobial resistance.
Antimicrobial resistance and the fight for our lives
In the battleground of infection, antibiotics and antivirals are our warriors. For over a century, they have been effective in defeating invading armies of bacteria and viruses, but more recently have fallen victim to their own success. Many microorganisms have encountered these same opponents so many times that they have evolved new tactics and greater protection against the onslaught of antimicrobial attacks. As such, the so-called superbugs that most antibiotics and antivirals are tasked to defeat are now too powerful for our war-weary weapons. The WHO casts this antimicrobial resistance (AMR) as a global health emergency and one of the most urgent public health issues affecting the world’s population.
These superbugs are appearing and spreading with truly worrying velocity. The starkest example being Extensively Drug Resistant Tuberculosis (XDR-TB), the most virulent and drug resistant strain of TB. First discovered in 2006, by 2016 it was detected in 121 countries, is resistant to all four core anti-TB drugs available and causes fatalities in 28% of infections. The WHO also reports that many antibiotics and antivirals no longer hold any therapeutic benefit against infections of HIV, E.coli, Staphylococcus aureus and malaria. If this hasn’t worried you already, the WHO makes it clear in its 2017 report that there aren’t enough antibacterial agents in clinical development to keep ahead of AMR.
With the slow-moving development of new antimicrobials, the battle against superbugs at the patient level is floundering. At the moment, our usual method of treatment is to increase the doses of existing first-line antimicrobials, and once those prove to be ineffective, patients are prescribed the second-line drugs. When those fail, we move on to third-line and continue escalating until they receive the antimicrobials of last resort. The medications above first-line drugs are often increasingly more expensive, and while this is a significant budget strain on health services in developed nations, it is often an expense the developing world simply can’t afford. This results in prolonged illness and death for millions of the world’s poorest from once easily defeated infections.
Can retrospective research deliver new antimicrobial weapons to the frontline?
The need to develop new antimicrobials faster is clear, but how can we successfully expedite drug discovery and delivery to get more effective drugs on the frontline in clinics? One thought is to look back at research of the past to help uncover forgotten microbial weapons.
Researchers around the world are analyzing old antibiotics developed and patented in the past that were not brought to market because they needed further development before they could be used in clinics. An example is linezolid, discovered by Du Pont in 1970. Despite being a powerful antibiotic, it was shelved when it was found to cause liver toxicity. Two decades later, Pharmacia & Upjohn (now Pfizer) redeveloped linezolid to make it safe and it’s now the lead drug against methicillin-resistant Staphylococcus aureus (MRSA) with sales in excess of $1 billion in 2010.
By applying today’s analytical techniques, we can uncover new insights about mechanisms of action to resurrect antimicrobials from the scientific graveyard. For instance, the Hudson Institute of Medical Research in Australia researched acriflavine, a compound extracted from coal tar and used as a topical antibiotic in the trenches of World War I before being replaced by penicillin in the 1950s. With the help of modern technology, researchers were able to see that this antibiotic additionally stimulates the immune system at the same time as killing the bacteria, providing a powerful double-punch against an infection. The interest in acriflavine is a reminder that there is still much we don’t know about the drugs we decided to discard 50 or more years ago, and that they were often thrown on the scrapheap for commercial, not scientific reasons.
Tools to enable effective retrospective search for antibiotics
Effectively revisiting drugs of the past isn’t easy. Finding forgotten molecules with the potential for further development can take time, particularly if you don’t have dedicated resources. If you’re thinking of resurrecting old antimicrobials, explore the use of dedicated research tools to make sure you’re accessing all available data as efficiently as possible.
We have become so accustomed to finding information instantly in digital format that we sometimes assume that every piece of research from yesteryear made the jump into the electronic era. While true in many cases, information solutions such as SciFindern from CAS, with content extending back into the pre-digital age, have become vital resources for finding so-called 'forgotten' science.
Additionally, ChemZentTM provides researchers access to a digital and English-searchable version of Chemisches Zentralblatt, the oldest German scientific publication of chemistry abstracts started in 1830 and continued until 1969. The ChemZent collection makes it possible to perform substance and topic searches on research from more than a century ago. In this way, ChemZent offers scientists a chance to rediscover forgotten research on promising compounds that could hold enormous potential.
Many discarded antibiotics have been patented, but these patents are often not discoverable, and the important chemistry can remain hidden. SciFindern makes finding archived antibiotics easy, with an extensive collection of patents and annotated compounds of interest. Additionally, the integration of SciFindern means that patent, non-patent literature and collections like ChemZent can all be compared simultaneously.
As a division of the American Chemical Society, CAS dedicated to improving people's lives through the transforming power of chemistry. To combat this urgent global health issue, we provide the solutions and resources needed to help scientists deliver new insights from archived research.
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