Infectious Disease experts say we are on the brink against pathogenic microorganisms, antibiotics and other antimicrobials, unless the healthcare industry and policy-makers significantly improve efforts to preserve these drugs’ effectiveness.

The mainstays of antimicrobials have been the β-lactam antibiotics, which include penicillin and methicillin. These antibiotics confer their bacteriocidal effect by inhibiting penicillin-binding proteins (PBPs) that are required for peptidoglycan biosynthesis and bacterial cell wall integrity. Resistance can be conferred through a number of mechanisms but broadly speaking is either due to bacteria acquiring enzymes capable of chemically inactivating the antibiotics (e.g. β-lactamases) or PBPs that show greatly reduced affinity for β-lactam antibiotics and hence reduced sensitivity to their inhibitory effects.

Amongst Gram-positive organisms, the most important resistant microorganisms in the ICU are currently multi-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (Referencers 3, 4). During the past decades, a shift in the multi-drug resistance (MDR) dilemma has been noted from Gram-positive to Gram-negative bacteria, especially due to the scarceness of new antimicrobial agents active against resistant Gram-negative microorganisms (Reference 4). In Gram-negative bacteria, a key resistance is the rapid increase of extended-spectrum β-lactamases (ESBLs) positive Klebsiella pneumonia and Escherichia coli; and more recently the emergence of carbapenem resistance. The rapid rise in carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter spp. has also become a critical issue for treating serious infections (Reference 5).  This resistance to antibiotics is responsible for a large number of hospital-acquired infections leading to significant clinical complications and patient mortality.

Amongst Gram-positive organisms, the most important resistant microorganisms in the ICU are currently multi-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (Referencers 3, 4). During the past decades, a shift in the anti microbial resistance dilemma has been noted from Gram-positive to Gram-negative bacteria, especially due to the scarceness of new antimicrobial agents active against resistant Gram-negative microorganisms (Reference 4). In Gram-negative bacteria, a key resistance is the rapid increase of extended-spectrum β-lactamases (ESBLs) positive Klebsiella pneumonia and Escherichia coli; and more recently the emergence of carbapenem resistance. The rapid rise in carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter spp. has also become a critical issue for treating serious infections (Reference 5).  This resistance to antibiotics is responsible for a large number of hospital-acquired infections leading to significant clinical complications and patient mortality.

Our approach to tackling anti microbial resistance

Blueberry is pursuing a long-term strategy of developing new antibiotics and their companion diagnostics alongside drugs specifically designed as “antibiotic resistance breakers”.

Antibiotic Resistance Breakers

We are developing a range of drugs that directly target mechanisms of bacterial resistance. By doing this we can restore sensitivity of bacteria to standard antibiotics. Some current treatments such as Augmentin (amoxicillin plus the beta-lactamase inhibitor clavulanic acid) utilize this strategy. At Blueberry we are developing approaches using both small and large molecules (e.g. peptide-aptamers) to target a range of different mechanisms of resistance with the aim of restoring bacterial susceptibility to previously effective antibiotics.

Developing New Antibiotics

In addition to targeting resistance mechanism we are also developing new antibiotics. These drugs target well-validated antibacterial mechanisms (for example cell wall biosynthesis) but with completely different pharmaceutical entities, which would therefore not be prone to current mechanisms of resistance.

Creating a sustainable response to antibiotic resistance

Together with advances in point-of-care diagnostics we believe that we can create a sustainable response to resistance that exploits the rapid development potential of protein aptamers to produce tailored therapies.

Antibiotic Resistance Chart

Achieving sustainable response to antibiotic resistance

The rapid development loop of aptamers, coupled to standard formulations allow us to develop a aptamer treament panel which can be used to deliver tailored therapies and is able to respond to emerging resistance.

References

2. Pyrek KM. Posted in: Articles, Antibiotic Stewardship, Antibiotic Resistance, Multidrug-Resistant Organisms (MDROS), PPE & Standard Precautions.

3. Arias CA, Murray BE. Nat Rev Microbiol. 2012 Mar 16:10(4):266-78.

4. Boucher HW et al. Clin Infect Dis 2009, 48:1-12.

5. Walsh TR. Int. J. of Antimicrobial Agents 2010 36:S8-S14