Molecular epidemiology and clinical characterization of carbapenemase-producing Enterobacter spp. from an international cohort

Jianping Jiang, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Lauren Komarow, The Biostatistics Center, George Washington University, Rockville, Maryland, USA.
Carol Hill, Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
Angelique E. Boutzoukas, Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
Blake Hanson, Center for Infectious Diseases and Microbial Genomics, UTHealth, McGovern School of Medicine at Houston, Houston, Texas, USA.
Cesar A. Arias, Division of Infectious Diseases and Center for Infectious Diseases Research, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, Texas, USA.
Robert A. Bonomo, Case Western Reserve University -VA Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Department of Medicine, Pharmacology, Molecular Biology and Microbiology, and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Scott Evans, The Biostatistics Center, George Washington University, Rockville, Maryland, USA.
Yohei Doi, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Michael J. Satlin, Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
Gregory Weston, Division of Infectious Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Eric Cober, Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Sandra Liliana Valderrama-Beltran, Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogota, Colombia.
Soraya Salcedo Mendoza, Servicio de Infectología, Clinica General del Norte, Barranquilla, Colombia & Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla, Colombia.
Zhengyin Liu, Department of Internal Medicine, Peking Union Medical College Hospital, Beijing, China & Department of Infectious Disease, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
Bettina C. Fries, Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
Paul Ananth Tambyah, Infectious Diseases Translational Research Program, National University of Singapore, Singapore.
Henry F. Chambers, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Vance G. Fowler, Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
David van Duin, Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA.
Barry N. Kreiswirth, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Liang Chen, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.

Document Type

Journal Article

Publication Date

12-12-2024

Journal

The Journal of infectious diseases

DOI

10.1093/infdis/jiae616

Keywords

E. hoffmannii; E. xiangfangensis; Carbapenem-resistant Enterobacter spp; clinical characterization; molecular epidemiology

Abstract

BACKGROUND: Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections. METHODS: Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016-2018 with cultures positive for carbapenemase-producing Enterobacter spp. were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed. RESULTS: We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp. from 30 hospitals in 7 countries. Among the 136 isolates, eleven Enterobacter species were identified, with most isolates belonging to E. xiangfangensis (n=81, 60%) and E. hoffmannii (n=17, 13%), and carrying blaKPC (n=106, 78%) and blaNDM (n=12, 9%). Clinical characteristics and outcomes were similar among patients with E. xiangfangensis, E. hoffmannii or the other Enterobacter spp. 30-day mortality was 20% and older age at enrollment (adjusted odds ratio 1.42, 95% confidence interval 1.08-1.87) was associated with increased mortality. Sequence type (ST)171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination. CONCLUSIONS: Our findings demonstrated that E. xiangfangensis and E. hoffmannii are common species among international carbapenemase-producing Enterobacter spp., potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.

Department

Biostatistics and Bioinformatics

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