Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States.
Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistantEnterobacteriaceae(CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance amongEnterobacteriaceaebloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance amongKlebsiella pneumoniae,Enterobacterspp., andEscherichia colibacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE wereK. pneumoniaeand 92% producedK. pneumoniaecarbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producingK. pneumoniae(KPC-Kp). Thewzi154allele, corresponding tocps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kphad greatercpsdiversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kphad an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kpbacteremia (adjusted odds ratio [aOR], 2.58;P= 0.045), cancer (aOR, 3.61,P= 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79;P= 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA mjs9012@med.cornell.edu.
Michael J
MJ
Satlin
Public Health Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Liang
L
Chen
Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Gopi
G
Patel
Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Angela
A
Gomez-Simmonds
Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York, USA.
Gregory
G
Weston
Division of Infectious Diseases, Northwell Health, Manhasset, New York, USA.
Angela C
AC
Kim
Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Susan K
SK
Seo
Department of Medicine, Jersey Shore University Medical Center, Neptune City, New Jersey, USA.|Department of Medicine, St. Peter's University Hospital, New Brunswick, New Jersey, USA.
Marnie E
ME
Rosenthal
Division of Infectious Diseases, Hackensack University Medical Center, Hackensack, New Jersey, USA.
Steven J
SJ
Sperber
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
Stephen G
SG
Jenkins
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Camille L
CL
Hamula
Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Anne-Catrin
AC
Uhlemann
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
Michael H
MH
Levi
Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York, USA.|Division of Infectious Diseases, Stony Brook University Medical Center, Stony Brook, New York, USA.
Bettina C
BC
Fries
Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Yi-Wei
0000-0003-4888-6771
YW
Tang
Department of Pathology, Northwell Health, Manhasset, New York, USA.
Stefan
S
Juretschko
Department of Pathology, Jersey Shore University Medical Center, Neptune City, New Jersey, USA.
Albert D
AD
Rojtman
Department of Pathology, Hackensack University Medical Center, Hackensack, New Jersey, USA.
Tao
T
Hong
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
Barun
B
Mathema
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Michael R
MR
Jacobs
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.|Departments of Pediatrics and Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA.
Thomas J
TJ
Walsh
Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.|Department of Medicine, Pharmacology, Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Robert A
RA
Bonomo
Public Health Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Barry N
BN
Kreiswirth
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D015780:Carbapenems / Q000494:pharmacology*; D004754:Enterobacter / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology
D000900:Anti-Bacterial Agents; D015780:Carbapenems
carbapenem-resistant Enterobacteriaceae; clinical outcomes; molecular epidemiology; resistance mechanisms