158 - Intra- and Inter-hospital Epidemiology of Carbapenem-resistant klebsiella Pneumoniae in US Hospitals

Background: Carbapenem-resistant Enterobacterales (CRE) and specifically Klebsiella pneumoniae (CRKp) are a global threat. CRE rapidly spreading in a healthcare network may infect a distinct patient cohort or have higher virulence. We determined the impact of cluster assignment of CRKp on transmission dynamics and clinical outcomes.

Methods: CRACKLE-2 is a multi-site, prospective, observational cohort study of hospitalized patients with a clinical CRE culture from any anatomic site. We analyzed 351 patients enrolled 4/30/2016-8/31/2017 in 42 US hospitals with clonal group 258 CRKp. Static clusters were set as ≤ 21 core single nucleotide polymorphisms (SNPs), identified by Snippy, and sharing a recent common ancestor, using a maximum likelihood phylogeny (RAxML v8.2.4). Dynamic clusters were set as > 80% probability of being within 3 transmissions by the R program transcluster (λ = 4, β = 1.6). Clinical outcome was assessed by desirability of outcome ranking with best outcome as alive without events and worst outcome as death. Events were no clinical response, unsuccessful discharge, and adverse events. We compared patients in and out of clusters. For patients in clusters, we also compared intra- vs inter-hospital clusters.

Results: In total, there were 49 static (median: 5, IQR: 2, 8) and 45 dynamic clusters (median: 5, IQR: 2, 20). For static clusters, 176 patients (50%) were in clusters with 82 (47%) patients in intra-hospital clusters. A higher proportion of patients in clusters, vs not in clusters, had a CRKp culture > 3 days from admission (P = 0.037). More patients in inter-hospital, vs intra-hospital, clusters had diabetes (P = 0.02). For dynamic clusters, 179 patients (51%) were in clusters with 69 (39%) patients in intra-hospital clusters. A lower proportion of patients in clusters, vs not in clusters, had CRKp isolated from urine (P = 0.04). More patients in inter-hospital, vs intra-hospital, clusters had a CRKp culture 3 days from admission (P = 0.04). Clinical outcomes were the same for patients in clusters vs not in clusters for static and dynamic clusters.Figure 1. Phylogenetic population structure of K. pneumoniae CG258 strains
Figure 2. Dynamic cluster structure of K. pneumoniae CG258 strains


Conclusion: This analysis shows that clinical outcomes are independent of clustering assignment. Static clustering better represented nosocomial spread, based on a higher proportion of patients in clusters having a later CRKp culture.

Presenting Author(s)

• 

  Courtney L. Luterbach, PhD, MS

  Postdoctoral Research Associate
  University of North Carolina at Chapel Hill
  Chapel Hill, NC

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

  Slides Slides and Audio

Co-Author(s)

• LC

  Liang Chen, Ph.D.

  Dr.
  Hackensack-Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA
  Nutley, New Jersey

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• BH

  Blake Hanson, PhD

  Assistant Professor
  University of Texas Health Science Center
  Houston, Texas

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• ME

  Michelle Earley, MS

  Statistician
  George Washington University
  Rockville, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• LK

  Lauren Komarow, MS

  Biostatistician
  George Washington University
  Rockville, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• GW

  Gregory Weston, MD MSCR

  Assistant Professor
  Montefiore Medical Center and Albert Einstein College of Medicine
  Bronx, New York

  Disclosure: Allergan (Grant/Research Support)
• EC

  Eric Cober, MD

  Staff
  Cleveland Clinic
  Cleveland, Ohio

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  Julia Garcia Diaz, MD, MSc, FACP, FIDSA, CPI

  Dr
  University of Queensland/Ochsner Clinical School
  New Orleans, Louisiana

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  Keith S. Kaye, MD, MPH

  Professor of Internal Medicine, Director of Research, Division of Infectious Diseases
  University of Michigan Medical School
  Ann Arbor, MI

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  W. Charles Huskins, MD, MSc

  Professor of Pediatrics
  Mayo Clinic College of Medicine and Science
  Rochester, MN

  Disclosure: ADMA Biologics (Consultant)Pfizer, Inc (Consultant)
• JG

  Jason C. Gallagher, PharmD

  Clinical Professor
  Temple University School of Pharmacy
  Philadelphia, Pennsylvania

  Disclosure: Allergan (Consultant)Astellas (Consultant)Merck (Consultant)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant)
• 

  Robert A. Bonomo, MD

  Associate Chief of Staff for Academic Affairs
  Louis Stokes Cleveland VA Medical Center
  Cleveland, OH

  Disclosure: Entasis, Merck, Venatorx : Research Grant or Support
• CA

  Cesar A. Arias, M.D., MSc, Ph.D., FIDSA

  Professor
  CARMiG, UTHealth and Center for Infectious Diseases, UTHealth School of Public Health, HOU, TX ; Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, BOG, COL
  Houston, Texas

  Disclosure: Entasis Therapeutics : Scientific Research Study Investigator; MeMed : Scientific Research Study Investigator; Merck : Grant/Research Support
• BK

  Barry N. Kreiswirth, PhD

  Professor
  Hackensack Meridian Health
  Nutley, New Jersey

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  David van Duin, MD, PhD

  Associate Professor of Medicine
  University of North Carolina
  Chapel Hill, North Carolina

  Disclosure: Achaogen : Advisor or Review Panel member; Allergan : Advisor or Review Panel member; Astellas : Advisor or Review Panel member; MedImmune : Advisor or Review Panel member; Merck : Advisor or Review Panel member; NeuMedicine : Advisor or Review Panel member; Qpex : Advisor or Review Panel member; Roche : Advisor or Review Panel member; Sanofi-Pasteur : Advisor or Review Panel member; Shionogi : Advisor or Review Panel member; T2 Biosystems : Advisor or Review Panel member; Tetraphase : Advisor or Review Panel member