Development of Targeted Antibody Therapy to Reduce Antimicrobial Resistance-Related Morbidity and Mortality in the Erasmus Medical Centre

Blood culture infections are a major contributor to patient morbidity and
mortality in hospitals around the world, including here at Erasmus MC.
Worryingly, there has been an alarming increase in antibiotic resistance in the
previous decade, whereas the discovery of new antibiotics has almost stopped,
largely due to the high costs and the long (up to 10 years) *research to
market* development process. Therefore, new strategies are required for
preventing and treating current and emerging (antibiotic resistant) pathogens
that threaten individual patients. A novel mechanism for treating antimicrobial
resistant organisms is to utilize the immune system of patients via
immunotherapy, utilizing a pool of targeted and specific anti-bacterial
antibodies to support and activate the immune system to an infection (passive
immunization). This type of therapy could potentially reduce morbidity and
mortality associated with bacteremic infections, and help reduce our
over-reliance on antibiotics. In the TARAME pre-pilot study, the feasibility of
developing pools of protective antibodies for use in immunotherapy will be
investigated by identifying and generating complement activating antibodies
directed against Escherichia coli and Pseudomonas aeruginosa. Recent
publications have indicated that conserved antigens exist in both species of
bacteria and that immunotherapy could be a useful therapy against these 2 major
bacterial pathogens.

To identify and clone antibodies that can neutralize the bacterial pathogens
Escherichia coli and Pseudomonas aeruginosa.

The study design to be applied is a pilot study in adult wards of the Erasmus
MC involving 5 patients with culture-confirmed E. coli and 5 patients with
culture-confirmed P. aeruginosa sepsis. The estimated duration of inclusion is
24 months. The study involves one extra blood withdrawal, comprising 2 x 9 ml
blood samples taken 7-10 days after suspicion of infection, all from an
existing central venous catheter (CVC) and when the antibody response is
expected to peak.

Two extra 9ml tubes of blood will be drawn (comprising one extra blood
withdrawal of 2 x 9 ml blood samples taken 7-10 days after suspicion of
infection) from an already installed central venous catheter (CVC) from a
defined patient group presenting with sepsis in adult wards of the Erasmus MC.
This patient group is defined as those patients with a confirmed positive blood
culture result for the bacterial pathogens E. coli or P. aeruginosa. Further,
no blood samples will be taken unless informed consent from either the patient
or his/her legal representative has been obtained. There are no benefits for
study participants. However patients may benefit in the future if high affinity
antibodies can be identified and cloned for use as antibody therapy (passive
immunization) against sepsis caused by the bacterial pathogens E. coli or P.
aeruginosa.