Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study

• Type of Material: Article
• Authors: David van Duin, University of North Carolina; Cesar A Arias, UTHealth; Lauren Komarow, George Washington University; Liang Chen, Center for Discovery and Innovation; Blake M Hanson, UTHealth; Gregory Weston, Albert Einstein College of Medicine; Eric Cober, Cleveland Clinic; Omai B Garner, University of California Los Angeles; Jesse Jacob, Emory University; Michael J Satlin, New York-Presbyterian Hospital; Bettina C Fries, Stony Brook University; Julia Garcia-Diaz, Ochsner Clinic Foundation; Yohei Doi, University of Pittsburgh; Sorabh Dhar, Wayne State University; Keith S Kaye, University of Michigan; Michelle Earley, George Washington University; Andrea M Hujer, Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Kristine M Hujer, Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Nicholas T Domitrovic, Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Willliam C Shropshire, UTHealth; Dinh An, UTHealth; Claudia Manca, Center for Discovery and Innovation; Courtney L Luterbach, University of North Carolina; Minggui Wang, Fudan University; David L Paterson, University of Queensland; Ritu Banerjee, Vanderbilt University; Robin Patel, Mayo Clinic; Scott Evans, George Washington University; Carol Hill, Duke University; Rebekka Arias, Duke University; Henry F Chambers, University of California San Francisco; Vance G Fowler, Duke University; Barry N Kreiswirth, Center for Discovery and Innovation; Robert A Bonomo, Louis Stokes Cleveland Department of Veterans Affairs Medical Center
• Language: English
• Date: 2020-06-01
• Publisher: ELSEVIER SCI LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/S1473-3099(19)30755-8
• Title of Journal or Parent Work: LANCET INFECTIOUS DISEASES
• Volume: 20
• Issue: 6
• Start Page: 731
• End Page: 741
• Grant/Funding Information: This study is supported by the National Institute of Allergy And Infectious Diseases of the National Institutes of Health (NIAID) under Award Number UM1AI104681. NIAID had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript nor the decision to submit the manuscript for publication, or to veto publication, or to control which journal the paper was submitted to.
• Keywords: EXPANSION; HOSPITALS; KLEBSIELLA-PNEUMONIAE; BLOOD-STREAM INFECTION; SURVEILLANCE; Science & Technology; OUTCOMES; BACTERIA; ESCHERICHIA-COLI; Life Sciences & Biomedicine; UNITED-STATES; Infectious Diseases

Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA. Methods: CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227. Findings: 1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45–71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20–28) of these patients had died. Interpretation: Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales. Funding: National Institutes of Health.