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Observational Study
. 2020 Jun;20(6):731-741.
doi: 10.1016/S1473-3099(19)30755-8. Epub 2020 Mar 6.

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

David van Duin  1 , Cesar A Arias  2 , Lauren Komarow  3 , Liang Chen  4 , Blake M Hanson  5 , Gregory Weston  6 , Eric Cober  7 , Omai B Garner  8 , Jesse T Jacob  9 , Michael J Satlin  10 , Bettina C Fries  11 , Julia Garcia-Diaz  12 , Yohei Doi  13 , Sorabh Dhar  14 , Keith S Kaye  15 , Michelle Earley  3 , Andrea M Hujer  16 , Kristine M Hujer  16 , T Nicholas Domitrovic  16 , William C Shropshire  17 , An Dinh  17 , Claudia Manca  4 , Courtney L Luterbach  18 , Minggui Wang  19 , David L Paterson  20 , Ritu Banerjee  21 , Robin Patel  22 , Scott Evans  3 , Carol Hill  23 , Rebekka Arias  23 , Henry F Chambers  24 , Vance G Fowler Jr  25 , Barry N Kreiswirth  4 , Robert A Bonomo  26 ; Multi-Drug Resistant Organism Network Investigators
Affiliations
Observational Study

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

David van Duin et al. Lancet Infect Dis. 2020 Jun.

Erratum in

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.

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Figures

Figure 1.
Figure 1.. CDC-defined CRE admission rates at participating hospitals.
The rates of all admissions during which CRE were identified (blue), and of admissions during which at least one CRE infection was diagnosed (red) are shown. CDC-defined CRE admission rates and robust 95% CIs were estimated using a generalized linear mixed effects model with hospital as a random effect. Error bars indicate 95% confidence intervals.
Figure 2.
Figure 2.. Phylogenetic population structures.
Circle 1 shows clonal groups (CG, 2.A.), Genomic clusters (2.B.), and Sequence Types (ST, 2.C.), Circle 2. indicates region of origin, Circle 3 CPE vs. non-CP-CRE vs. U-CRE, Circle 4 indicates carbapenemase present where applicable and Circle 5 indicates the DOOR level (Level 1; alive without deleterious events. Level 2; alive with 1 deleterious event. Level 3; alive with 2 or 3 deleterious events. Level 4; death). A. K. pneumoniae B. Enterobacter spp. C. E. coli. Of note, an interactive version of this Figure is available online (http://arlg.med.unc.edu/crackle/ password: B@ct3r1@).
Figure 2.
Figure 2.. Phylogenetic population structures.
Circle 1 shows clonal groups (CG, 2.A.), Genomic clusters (2.B.), and Sequence Types (ST, 2.C.), Circle 2. indicates region of origin, Circle 3 CPE vs. non-CP-CRE vs. U-CRE, Circle 4 indicates carbapenemase present where applicable and Circle 5 indicates the DOOR level (Level 1; alive without deleterious events. Level 2; alive with 1 deleterious event. Level 3; alive with 2 or 3 deleterious events. Level 4; death). A. K. pneumoniae B. Enterobacter spp. C. E. coli. Of note, an interactive version of this Figure is available online (http://arlg.med.unc.edu/crackle/ password: B@ct3r1@).
Figure 2.
Figure 2.. Phylogenetic population structures.
Circle 1 shows clonal groups (CG, 2.A.), Genomic clusters (2.B.), and Sequence Types (ST, 2.C.), Circle 2. indicates region of origin, Circle 3 CPE vs. non-CP-CRE vs. U-CRE, Circle 4 indicates carbapenemase present where applicable and Circle 5 indicates the DOOR level (Level 1; alive without deleterious events. Level 2; alive with 1 deleterious event. Level 3; alive with 2 or 3 deleterious events. Level 4; death). A. K. pneumoniae B. Enterobacter spp. C. E. coli. Of note, an interactive version of this Figure is available online (http://arlg.med.unc.edu/crackle/ password: B@ct3r1@).
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Comment in

References

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