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Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study - 08/06/20

Doi : 10.1016/S1473-3099(19)30755-8 
David van Duin, MD a, *⁎ , Cesar A Arias, MD b, c, d, *, Lauren Komarow, MS e, Liang Chen, PhD f, Blake M Hanson, PhD b, c, Gregory Weston, MD g, Eric Cober, MD h, Omai B Garner, PhD i, Jesse T Jacob, MD j, Michael J Satlin, MD k, Bettina C Fries, MD l, Julia Garcia-Diaz, MD m, Yohei Doi, MD n, o, Sorabh Dhar, MD p, Keith S Kaye, MD q, Michelle Earley, MS e, Andrea M Hujer, BS r, s, Kristine M Hujer, BS r, s, T Nicholas Domitrovic, MS r, s, William C Shropshire, BS b, An Dinh, BS b, Claudia Manca, PhD f, Courtney L Luterbach, PhD a, Minggui Wang, MD t, David L Paterson, MD u, Ritu Banerjee, MD v, Robin Patel, MD w, Scott Evans, PhD e, Carol Hill, PhD x, Rebekka Arias, BS x, Henry F Chambers, MD y, Vance G Fowler, MD x, z, Barry N Kreiswirth, PhD f, †, Robert A Bonomo, MD r, s, aa, ab, †
for the

Multi-Drug Resistant Organism Network Investigators

a Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA 
b Division of Infectious Diseases and Center for Antimicrobial Resistance and Microbial Genomics, UTHealth, Houston, TX, USA 
c Center for Infectious Diseases, UTHealth, Houston, TX, USA 
d Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia 
e The Biostatistics Center, The George Washington University, Rockville, MD, USA 
f Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA 
g Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA 
h Department of Infectious Diseases, Cleveland Clinic, Cleveland, OH, USA 
i Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA 
j Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA 
k Division of Infectious Diseases, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA 
l Department of Medicine, Division of Infectious Diseases, Stony Brook University, Stony Brook, NY, USA 
m Department of Infectious Diseases, Ochsner Clinic Foundation, New Orleans, LA, USA 
n Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 
o Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Aichi, Japan 
p Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA 
q Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA 
r Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA 
s Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA 
t Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China 
u University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital Campus, QL, Australia 
v Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA 
w Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, and Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA 
x Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA 
y Department of Medicine, University of California San Francisco, San Francisco, CA, USA 
z Division of Infectious Diseases, Duke University, Durham, NC, USA 
aa Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA 
ab CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology, Cleveland, OH, USA 

* Correspondence to: Dr David van Duin, Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA Division of Infectious Diseases University of North Carolina Chapel Hill NC 27599 USA

Summary

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.

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Vol 20 - N° 6

P. 731-741 - juin 2020 Retour au numéro
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