Antimicrobial resistance (AMR) has been heralded as “one of the biggest health threats facing mankind” by the O’Neill review. EPM looks at five ways in which the pharmaceutical sector is fighting this threat
Antibiotic alternatives: Staphefekt
Micreos has secured £9.3m (€12m) for the development of products containing Staphefekt, an alternative to antibiotics that treats bacterial colonisation on skin.
Gladskin is a lysin based product registered for human use and specifically targets S.aureus bacteria on intact skin. Staphefekt was first used in Gladskin, a product for people with inflammatory skin conditions such as eczema, rosacea and acne.
Contrary to antibiotics, Staphefekt kills only the harmful bacteria, leaving the beneficial microbiome on skin unharmed.
Repurposing existing therapies
The Antibiotic Research UK (ANTRUK) charity has launched a research programme to test whether existing therapies for the treatment of medical conditions can reverse the antibiotic resistance of superbugs.
ANTRUK’s programme challenges the rise in antibiotic resistant bacteria (superbugs) by screening antibiotic resistance breakers against antibiotic resistance in Gram-negative bacteria.
The charity asked scientific organisations and universities to submit tenders for this testing to see if therapies already in use and being safely administered in humans can be co-administered with antibiotics.
This is the first of five projects that will be carried out in the next five to seven years, with the ultimate objective of developing new antibiotic therapies for use by the early 2020’s to overcome superbugs, according to ANTRUK.
Antibiotic alternatives: Viruses that eat bacteria
C. diff is one of the natural microbes found in your gut, but chronic antibiotic use can make it go haywire. It’s also one of the many superbugs turning up at hospitals. It caused 14,000 deaths and 250,000 hospitalisations between 2005 and 2011, according to the Centers for Disease Control and Prevention (CDC).
Specialists at the University of Leicester and AmpliPhi Biosciences Corporation have found phages, viruses that eat bacteria, to specifically target C. diff. They work by attaching to bacteria as a host, injecting their DNA—which replicates—and causing the bacterial cell to burst open.
AmpliPhi is funding the development of these C. diff phages and hopes to have a mixture ready for clinical trials soon.
Phenotypic and target-based screening
Phenotypic screening for bioactive compounds that kill bacteria has been the mainstay for antibiotic discovery for the past century and has recently found favour again.
Researchers can identify chemicals with antibacterial activity. However the mechanism of action for the bioactive compounds must be addressed before further development can proceed and is an important hurdle to overcome.
Target-based screening uses structural biology and drug design, compounds that bind to the target and can quickly enter medicinal chemistry programmes.
While the jury is still out on their ability to completely solve AMR, phenotypic and target-based screening may have a significant role to play.
Antibiotic Alternative: PPMOs
Researchers at Oregon State University and other institutions say bacteria’s new worst enemy may be a peptide-conjugated phosphorodiamidate morpholino oligomer, or PPMO. These lab-synthesised forms of DNA or RNA are said to function better than a standard antibiotic without the risk of bacteria becoming resistant to them.
Unlike antibiotics, which attack a bacteria cell’s function and can cause other side effects, PPMOs disrupt the bacteria’s genes. Issues of toxicity need to be addressed in further testing before PPMOs can be used in humans, the researchers said.