Research

Our initial focus is on Carbapenem and Extended-spectrum β-lactamase resistant (CBE and ESBL) E. coli, by far the predominant cause of urinary tract infections and a leading cause of bloodstream infections.

Cobio’s approach can be applied to any bacterial phylotype for which a lytic phage exists (and such phages have been reported for most if not all human pathogens). We strive to develop our technology for rapid diagnostics of a variety of urgent targets, most specifically the ESKAPE pathogens: Enterococcus faecalis and faecium (VRE), Staphylococcus aureus (MRSA), Klebsiella pneumonia (KPC), Acinetobacter, Pseudomonas, and Enterobacter, which encompass both Gram-negative and -positive priority pathogens exhibiting increasingly difficult to treat CBE and ESBL mutltidrug resistant infections.

Preliminary data show that our phage-amplified approach is capable of detection, ID, AST and MIC within 5 hours. Comparable non-phage approaches require incubation times of 18-72 hours and have variable accuracies. This leads to inappropriate treatment, longer hospital stays and greater costs in clinical situations where the odds of mortality from drug resistant blood stream infection increase 7% per hour for every hour that effective therapy is delayed. New tests that provide these vital pieces of information are therefore in high demand in the face of the increasing global incidence of drug resistant infections. Our approach is ideally positioned to meet this demand.

Background and Significance

CBE and ESBL E. coli. E. coli are major contributors to nosocomial and community-acquired illness and are the leading etiologic agent of increasingly problematic multidrug resistant (MDR) urinary tract (UTI), bloodstream and diarrheagenic GI tract infections (1). It is estimated that there are at least 150 million UTIs each year worldwide (2). Of the 10.5 million UTIs reported in the just the U.S. per year, at least 10% are antibiotic resistant. A large majority (~80%) of these are caused by uropathogenic E. coli. If these infections are not rapidly diagnosed accurately and treated appropriately they result in significantly higher rates of morbidity and mortality, increased length of hospitalization and significantly higher healthcare costs. Death is the ultimate outcome in as high as 50% of infections of critically ill inpatients. CBE and ESBL E. coli serve as just one prime example of a problematic Gram-negative associated with high rates of increasingly AMR infection.

Diagnostic challenges presented by MDR Gram-negative pathogens. Two longstanding challenges associated with clinical bacterial diagnostics that greatly limit the current state-of-the art are: 1) the fundamental reliance of current approaches on lengthy culture (typically 24-72 hours depending on the organism) and 2) the lack of tractable capacity in the era of increasingly problematic multidrug resistance to perform both ID and AMR testing with the same test.  It has been well established that highly accurate and more rapid (1-5 hour) diagnostic tests result in significantly lower treatment costs, shorter lengths of hospitalization, and better patient outcomes. A significant limitation with widely investigated genotypic molecular approaches, particularly with regards to Gram negative pathogens is that, due to the varied mechanisms utilized by these organisms to evolve resistance, phenotypic approaches are critical to accurately determine susceptibilities. There are no rapid phenotypic approaches currently available in the clinical setting.

Further, immunoassays that detect a host immune response or other more specific target antigens, lack sensitivity compared to existing FDA cleared, protein profiling-based MALDI-TOF MS systems already heavily in use around the world. Such MALDI platforms, which have quickly changed routine microbial diagnostics with relatively rapid throughput and high-level accuracy, still are culture dependent and lack the capacity to perform MDR testing.