—Centers for Disease Control and Prevention (CDC)
VenatoRx is primarily targeting CRE (Carbapenem-Resistant Enterobacteriaceae) and CR-PA (Carbapenem-Resistance Pseudomonas aeruginosa). Both have been termed ‘super-bugs’ due to their resistance to virtually all known antibiotics.
Antibiotic-resistant bacteria pose a significant challenge to patients, physicians, and health organizations. In the United States, over 2 million people acquire infections annually from antibiotic resistant bacteria. Over 250,000 of these people require hospitalization, costing the US healthcare system over $21 billion per year.1,2 In Europe, antibiotic-resistant bacterial infections cause over 20,000 deaths per year and cost over €1.5 billion per year.3 A 2014 study commissioned by the UK estimates that annual world-wide deaths attributable to antibiotic-resistant infections will rise from a current 700,000 to 10 million by 2050 if action to counter this crisis is not taken immediately.4
Due to the increased use of antibiotics in a growing immuno-impaired population (those with advanced age, cancer, organ transplant or diabetes) and rapid dispersion of resistant organisms through travel, drug-resistant organisms have become increasingly common. VenatoRx is primarily targeting CRE (Carbapenem-Resistant Enterobacteriaceae) and CR-PA (Carbapenem-Resistance Pseudomonas aeruginosa). The latter have been termed ‘super-bugs’ due to their resistance to virtually all known antibiotics. Notably, CRE and CR-PA have been named two of the most urgent three priority pathogens by WHO5 and declared Urgent and Serious drug-resistant threats, respectively, by CDC.6 In addition, VenatoRx is engaged in biodefense efforts against less commonly known bacterial organisms such as Salmonella spp, Shigella spp, Vibrio spp, Burkholderia mallei, and Burkholderia pseudomallei, which could be deliberately engineered for resistance and used as biological weapons.
Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria that are resistant to all known unprotected beta-lactam antibiotics, including penicillins, cephalosporins, monobactams, and carbapenems. Enterobacteriaceae frequently are the causative pathogens for urinary tract and intra-abdominal infections. A recent study showed up to 50% mortality rate for patients who developed septicemia from an underlying CRE infection.7
Carbapenem resistance in CREs is driven primarily by bacterial production of a continuously- expanding class of enzymes known as beta-lactamases that break down and inactivate beta-lactam antibiotics. As of 2017, over 2,000 beta-lactamases have been identified and classified. Bacteria are able to share the genetic information for synthesis of these enzymes, resulting in dissemination of broad resistance. Today, the frequency of CRE bacteria is growing rapidly. A University of Pittsburgh study reported a 400% increase in CRE occurrence between 1999 and 2010.8
Carbapenem-Resistant Pseudomonas aeruginosa
Carbapenem-resistant Pseudomonas aeruginosa (CR-PA) are another sub-group of gram-negative bacteria that are increasingly resistant to beta-lactams. Pseudomonas is frequently a causative pathogen in wound infections and some subtypes of serious respiratory tract infections as well as sporadically in urinary tract infections. Beta-lactam resistance in CR-PA is also driven by beta-lactamase activity as well as bacterial mechanisms that limit antibiotic permeability.
2. White, A.R. Effective Antibacterials: at What Cost? The Economics of Antibacterial Resistance and its Control. In Journal of Antimicrobial Chemotherapy, 2011, 66(9): 1948-53.
3. “Burden of Antibiotic Resistance.” Action on Antibiotic Resistance (ReAct), www.reactgroup.org/uploads/publications/react-publications/ReAct-facts-burden-of-antibiotic-resistance-May-2012.pdf, 2012.
4. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations (amr-review.org/ )
6. ANTIBIOTIC RESISTANCE THREATS in the United States, 2013
7. Borer, A., Lisa Saidel-Odes, M. D., Riesenberg, K., et al. Attributable Mortality Rate for Carbapenem-resistant Klebsiella Pneumoniae Bacteremia. In Infection Control and Hospital Epidemiology, 2009, 30:972-6. CDC.
8. CDC Morbidity and Mortality Weekly Reports 130308 (v26n9)