Clinical Need

Bacterial bloodstream infections (BSI), in general,   are one of the top causes of death in North America and Europe, with an estimated annual incidence of up to 677,000 cases in North America and up to 1,200,000 cases in Europe. (4) With mortality rates as high as 50% for certain bloodstream infections, (5)  the continued emergence of drug-resistant pathogens, and fewer anti-infective drugs in development, ExThera sees a critical need to address this growing global health problem.

Once bacteria enter the bloodstream from a local site of infection, they can then be disseminated throughout the body, leading to metastatic complications such as endocarditis, meningitis, and osteomyelitis. If not treated properly, uncontrolled infections quickly lead to a dysfunctional host response.. Disease progression may lead to sepsis, septic shock, and ultimately death.

Staphylococcus aureus, P. aeruginosa and Enterobacteriaceae are the most common bacteria responsible for bacteremia and nosocomial infections.  Severity of outcome for bacteremic patients depends on both the bacterial load and the duration of bacteremia.

Dialysis patients are at high risk of developing bloodstream infection, due to long-term vascular access to the bloodstream. Sixty percent of BSI's in dialysis patients are caused by Staphylococcus aureus. Increasingly, drug-resistant strains of these bacteria, known as Methicillin Resistant Staphylococcus aureus (MRSA), are implicated.

In preclinical studies, ExThera’s scientists have demonstrated that many toxins, inflammatory cytokines and a wide variety of bacteria and viruses are captured by Seraph when whole blood or serum is passed through the device. Notably, in vitro studies have demonstrated that both S. aureus and MRSA are bound to the Seraph hemofilter's adsorption media as blood passes over it, allowing the concentration of bacteria in the bloodstream to be reduced by up to 85 percent in just a single pass of contaminated blood. A typical four-hour treatment using continuous recirculation of blood through the Seraph device can therefore result in >99% reduction in the concentration of bacteria in the patient’s bloodstream. Reducing pathogen load in blood should lower the body's risk of metastatic infection and a dysfunctional systemic host  response stemming from the release of a variety of virulence factors, toxins, and cytokines. 

Read the latest on the emerging threats from drug resistant bacteria in the newly issued report from the Centers for Disease Control: ANTIBIOTIC RESISTANCE THREATS in the United States, 2013


Blood Banking

ExThera is  exploring a potential application for Seraph to purify blood for use by blood banks amidst the growing global threat of newly emerging pathogens.

In 2011, as reported by the American Association of Blood Banks (AABB) and Hospital for Special Surgery (HSS), 15.7 million blood transfusions were performed in the United States. While the U.S. blood supply is widely regarded as among the safest in the world, pathogens continue to evolve in ways that require vigilance, to maintain that record of success. The American Red Cross has published its concerns about high-risk emerging infectious disease agents that may pose a significant risk to the U.S. and Canadian blood supplies, which include West Nile virus, babesia and dengue fever.

Globally, the threats to the blood supply in poorer countries are far greater than in the U.S.  In 2011, there were a total of 92 million blood units donated worldwide. According to the World Health Organization (W.H.O.), 11 percent of all blood units donated were not screened for one or more viruses, including HIV, hepatitis B, and hepatitis C.  Of 164 countries that reported to WHO, 39 indicated that they do not routinely screen all of the blood transfused in their nation. In low-income countries, only 53% screen blood using basic quality procedures. In sub-Saharan Africa, 28 of the 40 countries have not implemented national quality assurance systems to screen blood. It is estimated that between 5 and 10 percent of all HIV cases are still caused by the transfusion of blood or blood products.

4)  Neuner, Elizabeth A., et al. "Treatment and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections." Diagnostic microbiology and infectious disease 69.4 (2011): 357-362.  

5) Goto, M., and M. N. Al‐Hasan. "Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe." Clinical Microbiology and Infection 19.6 (2013): 501-509.