Research

Carbapenem-resistant Enterobacteriaceae (CRE) are a major threat to our vulnerable patient populations. David van Duin, MD, PhD, began studying these pathogens at the onset of the epidemic in the Great Lakes area when he and his colleagues were confronted with these essentially untreatable infections. The molecular and clinical epidemiology of these infections has been described in the context of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1). CRACKLE is a federally funded, prospective multi-center consortium to track carbapenem-resistant Enterobacteriaceae of which Dr. van Duin is the principal investigator.

Data from CRACKLE-1 have shown that ST258 is the primary strain type of carbapenem-resistant K. pneumoniae, and that this ST258 strain type can be further subdivided into at least 2 specific clades which are distinct microbiologically and are associated with clinical outcomes. We have analyzed risk factors for and consequences of tigecycline and colistin resistance in CRE. In July 2016, with support from the Antibacterial Resistance Leadership Group (ARLG), CRACKLE-2 was started, with more than 60 hospitals worldwide participating.

Dr. van Duin and colleagues have also collaborated with the J. Craig Venter Institute.

The Team

David van Duin, MD, PhD, FACP, is an associate professor and the founding director of the Immunocompromised Host Infectious Diseases Program in the Division of Infectious Diseases at the University of North Carolina. Dr. van Duin earned his medical degree from the University of Amsterdam in the Netherlands. He completed his residency in internal medicine at Albert Einstein College of Medicine/Jacobi Medical Center. He then went on to a post-doctoral fellowship in infectious diseases at Yale School of Medicine.

In addition, he was awarded a doctor of philosophy degree in investigative medicine from Yale University. After fellowship, he joined the Department of Infectious Diseases at the Cleveland Clinic. He was awarded the GEMSSTAR Award from the National Institute on Aging, as well as the 2012 Association of Specialty Professors-Infectious Diseases Society of America Young Investigator Award in Geriatrics. He joined the Division of Infectious Diseases at UNC in June of 2013. His main research interests are multi-drug resistant gram-negative bacteria and infections in immunocompromised patients.


Heather Henderson, DVM, MPH, is a graduate research assistant with the Division of Infectious Diseases at UNC. She earned her veterinary degree at Auburn University and worked in private practice for several years before deciding on a career in public health. She completed her Master of Public Health degree at East Carolina University and has since worked in public health at the federal, state, and local levels. She is currently pursuing a PhD in epidemiology at UNC, with a focus on infectious diseases. Her primary interest is emerging infectious diseases. She has been with the CRACKLE team since January 2018, working with data cleaning and analysis.

Ashley Boshe is a research assistant with the Division of Infectious Diseases at UNC. She graduated from Missouri State University in 2014 with a B.S. in Cell and Molecular Biology. She has been with the CRACKLE team since February 2016 working with data collection and management. Ashley will be attending the University of North Carolina School of Medicine beginning August of 2018.

Courtney Luterbach, PhD, MS, is a postdoctoral research associate with the UNC Institute of Global Health & Infectious Diseases. She earned her PhD in microbiology and immunology at the University of Michigan and her MS in hospital and molecular epidemiology at the University of Michigan School of Public Health. Her primary interests are multi-drug resistant bacteria, disease transmission, and the molecular mechanisms of bacterial pathogenesis. She has been with the CRACKLE team working on data analysis since June 2018.

Laura Ruegsegger is a research assistant with the Division of Infectious Diseases at UNC since May 2018. She graduated from the Ohio State University with a Bachelor of Science in Public Health in 2017. She joined the CRACKLE and CA-CRE team in May 2018, consenting patients and working with data collection and management.
Ami Shiddapur is a research assistant with the Division of Infectious Diseases at UNC. She graduated from UNC in 2018 with a B.S. in biology. She joined the CRACKLE team in May 2018, and works with data collection and management.

Key Publications

  1. Rojas LJ, Salim M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Marshall S, Rudin SD, Domitrovic TN, Hujer AM, Hujer KM, Doi Y, Kaye KS, Evans S, Fowler VG, Bonomo RA, van Duin D. “Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality.” Clinical Infectious Diseases 2017;64(6):711-718.
  2. Hauck C, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Scalera NM, Doi Y, Kaye KS, Evans S, Fowler VG Jr, Bonomo RA, van Duin D; Antibacterial Resistance Leadership Group. “Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections.” Clinical Microbiology and Infection 2016;22(6);513-519
  3. van Duin D, Cober E, Richter SS, Perez F, Kalayjian RC, Salata RA, Evans S, Fowler VG, Kaye KS, Bonomo RA. “Impact of Therapy and Strain Type on Outcomes in Urinary Tract Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae.” Journal of Antimicrobial Chemotherapy, 2015;70:1203-11
  4. van Duin D, Perez F, Rudin SD, Cober E, Hanrahan J, Ziegler J, Webber R, Fox J, Mason P, Richter SS, Cline M, Hall GS, Kaye KS, Jacobs MR, Kalayjian RC, Salata RA, Segre JA, Conlan S, Evans S, Fowler VG Jr, Bonomo RA. “Surveillance of Carbapenem-Resistant Klebsiella pneumoniae: Tracking Molecular Epidemiology and Outcomes through a Regional Network.” Antimicrobial Agents and Chemotherapy. 2014: Jul;58(7):4035-41
  5. van Duin D, Cober E, Richter SS, Perez F, Cline M, Kaye KS, Kalayjian RC, Salata RA, Evans S, Fowler VG, Bonomo RA. “Tigecycline Therapy for Carbapenem-Resistant Klebsiella pneumoniae (CRKP) Bacteriuria Leads to Tigecycline Resistance.” Clinical Microbiology and Infection. 2014;20(12):O1117-20