We have discovered a new class of phage-encoded lytic antimicrobial peptides that have potent in vitro activity across a wide range of resistant Gram-negative pathogens, including species which are part of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Amurins have also shown the ability to clear biofilms and act synergistically with a range of standard-of-care antibiotics. In addition, amurins have demonstrated the same activity profile against Escherichia coli. This differentiated spectrum of activity would make the amurins extremely well suited as potential treatments for patients suffering from polymicrobial Gram-negative infections, such as cystic fibrosis, ventilator-associated pneumonia, intra-abdominal infections, and serious burns or certain chronic wound infections. In March 2019, ContraFect was awarded a $6.9 million grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to support the further development of the amurin peptide program.
The Enterobacteriaceae family of Gram-negative bacteria includes Klebsiella pneumoniae (K. pneumoniae), Enterobacter species (Enterobacter e.g. Enterobacter cloacae) and Escherichia coli (E.coli), all of which can cause serious, life-threatening infections, and have demonstrated concerning resistance patterns. An estimated 140,000 healthcare-associated Enterobacteriaceae infections occur in the United States each year.
For example, K. pneumoniae are common causes of serious, potentially life-threatening pneumonia, complicated urinary tract and intra-abdominal infections in hospital settings, particularly in intensive care units and among vulnerable patients with impaired immune systems, diabetes or alcohol-use disorders. The mortality rates for hospital-acquired pneumonia due to K. pneumoniae can exceed 50% in vulnerable patients.
Enterobacteriaceae pathogens are considered a critical priority by the World Health Organization and urgent and serious threats by the Centers for Disease Control and Prevention.
Acinetobacter baumannii (Acinetobacter) is a hospital-associated Gram-negative pathogen most commonly found in severe pneumonia, as well as bloodstream, urinary tract and wound infections. In the United States, roughly 63% of isolates from Acinetobacter infections are considered multidrug-resistant. Carbapenem resistance in some European and Asian countries is reported to be even higher, surpassing 80% in some cases.
Therefore, are few treatment options available to effectively treat patients with multidrug-resistant Acinetobacter infections. Use of colistin, a polymyxin class antibiotic, can be toxic to the kidney and nervous system. As a result, overall mortality of patients with multidrug-resistant Acinetobacter infections is close to 50%, and there is an emerging threat of Acinetobacter strains reported to be resistant to all available antibiotic therapies, including colistin, which is currently the last-resort treatment option.
Acinetobacter is considered a critical priority by the World Health Organization and a serious threat by the Centers for Disease Control and Prevention.
Exebacase is an investigational novel lysin being studied in clinical trials as a treatment for patients with Staph aureus bacteremia, including endocarditis, caused by MRSA or MSSA.View CF-301 »