©2019 by VanEpps Research Laboratory

There are 19 million world-wide cases of sepsis with more than a million in the U.S.  Rapid administration of appropriate antibiotics is the key to reducing morbidity and mortality.   However, blood cultures – the current standard of care for diagnosis, pathogen identification and antibiotic susceptibility testing (AST) – are limited by long time to result (>48hrs), low sensitivity and specificity, and limited viral or fungal identification.  In almost all cases, patients are started on empiric antibiotics design to cover most but not all of the most likely pathogens.  This one-size-fits-all use of antibacterial drugs leads to antibiotic resistance, severe side effects or under-treatment of critically ill patients.

We have developed a novel, ultrasensitive, polymerase chain reaction (PCR) detection system that couples standard PCR primers to gold nanorods (NR-PCR).  This method is at least 50 times more sensitive than the most sensitive PCR detection techniques currently available.  In addition, it is particularly sensitive for large (>2nm) DNA strands which improves the specificity of the assay. By coupling our ultrasensistive NR-PCR assay to pathogen specific genetic targets we intend to reduce the time to pathogen identification and antibiotic susceptibility to less than 3 hours. 

The collaboration established by the Michigan Medicine and Peking University Health Science Center Joint Institute has provided funding for this project.  The overarching goal of this two-year project is to translate NR-PCR to clinical application and perform the first human clinical trial of this assay.  Beyond accelerating the translation and adoption of a novel microbiological diagnostic, this partnership will (1)  reveal variations in practice patterns between the two institutions regarding diagnosis of suspected bloodstream infection; (2) increase the power and generalizability of this study by expanding the size and diversity of the patient cohort for assay testing; (3) will provide access to an at risk patient population (i.e., in China) where antibacterial resistance is rapidly growing; and (4) establish an infrastructure foundation for future international studies of sepsis diagnostics and potential therapeutics.  

 

Background: Sample of gold nanorods before and after PCR process

NanoRods-PCR