translational microbiology laboratory by j. scott vanepps
TRANSCRIPT
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J. Scott VanEpps, MD, PhD
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I have no conflicts of interest to disclose
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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
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Protection from host defense
Prevent diffusion of humoral factors
Kills neutrophils
Protection from antibiotics
Restricted diffusion
Reduced metabolic activity
Small molecule degradation
Persister cells
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Antimicrobial zinc oxide nanoparticles
Thermal treatment of biofilms in situ
Nanorod-PCR (NR-PCR) for rapid detection of bacteremia
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Pyramids Spheres Plates
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McGuffie et al., Nanomedicine, 2015
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McGuffie et al., Nanomedicine, 2015
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Sturtevant et al., Shock, 2015
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Richardson et al., ASAIO J, 2015
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Richardson et al., ASAIO J, 2015
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Richardson et al., ASAIO J, 2015
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Richardson et al., ASAIO J, 2015
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Chiroplasmonic Nanorod-PCR (NR-PCR) for rapid determination of bacteremia and antibiotic
resistance in sepsis
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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
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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
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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
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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
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NIH NIGMS MCubed MCIRCC SAEM NSF CVC DOD EMF
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