J. Scott VanEpps, MD, PhD

I have no conflicts of interest to disclose

Half of the 2 million annual healthcare-associated infections in the U.S. can be attributed to indwelling medical devices

Devices implanted by EPs Central lines

Endotracheal tubes

Foley catheters

Despite over a decade of effort, infected devices remain the most common cause of healthcare-associated bloodstream infection

Protection from host defense

Prevent diffusion of humoral factors

Kills neutrophils

Protection from antibiotics

Restricted diffusion

Reduced metabolic activity

Small molecule degradation

Persister cells

Antimicrobial zinc oxide nanoparticles

Thermal treatment of biofilms in situ

Nanorod-PCR (NR-PCR) for rapid detection of bacteremia

Pyramids Spheres Plates

McGuffie et al., Nanomedicine, 2015

McGuffie et al., Nanomedicine, 2015

Sturtevant et al., Shock, 2015

Richardson et al., ASAIO J, 2015

Richardson et al., ASAIO J, 2015

Richardson et al., ASAIO J, 2015

Richardson et al., ASAIO J, 2015

Chiroplasmonic Nanorod-PCR (NR-PCR) for rapid determination of bacteremia and antibiotic

resistance in sepsis

Scenario: Septic patient presents to the Emergency Department Fever, confused, elevated heart rate, decreased blood pressure What is the source? What is the bug? Which antibiotic?

Current goal: Administer broad spectrum antibiotics in the first hour De-escalate to targeted therapy ASAP1

Problem: Blood cultures are the current gold standard Long time to result (24-72hrs)2

Low sensitivity and specificity3

Limited viral and fungal identification3

Result: One-size-fits-all Antibiotic resistance (MRSA, VRE) Opportunistic infection (C. dificile) Life threatening side effects (renal and hepatic failure) Undertreatment of critically ill patients

Blood Sample

Culture (12-24hrs)

Speciation (12-24hrs)

Antibiotic Sensitivity (12-24hrs)

NR-PCR (≈3 hrs)Gram +/-

Organism

Targeted therapy

Blood Sample

Antibiotic resistance genes

Targeted therapy

Time to result = 36-72hrs Time to result ≈3 hrs

Organism

Best limit of detection: 160zM (10-21)

Best time to result: 2 hrs

What next: Compare to blood culture Evaluate CD wavelength vs

transcript length Develop melt curve equivalent Growth in presence of Abx

VanEpps Lab: Matt McGuffie Usha Kadiyala Rachael Sturtevant Nina Grossman Carolyn Vitale

Younger Lab: Prannda Sharma Ian Richardson Marika Raff

Solomon Lab: Elizabeth Stewart Maria Tianhui Joanne Beckwith

Michael Heung, MD Kotov Lab:

Jin Hong Joong Hwan Bahng Gleiciani Silveira

Yue Wang Green Lab:

Emmanouil Glynos

NIH NIGMS MCubed MCIRCC SAEM NSF CVC DOD EMF