Multicenter clinical and molecular epidemiological analysis of bacteremia due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States

Michael J. Satlin, Liang Chen, Gopi Patel, Angela Gomez-Simmonds, Gregory D. Weston, Angela C. Kim, Susan K. Seo, Marnie E. Rosenthal, Steven J. Sperber, Stephen G. Jenkins, Camille L. Hamula, Anne Catrin Uhlemann, Michael H. Levi, Bettina C. Fries, Yi Wei Tang, Stefan Juretschko, Albert D. Rojtman, Tao Hong, Barun Mathema, Michael R. JacobsThomas J. Walsh, Robert A. Bonomo, Barry N. Kreiswirth

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (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 among Enterobacteriaceae bloodstream 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 among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had 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-Kp bacteremia (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.

Original languageEnglish (US)
Article numbere02349-16
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Carbapenems
Enterobacteriaceae
Bacteremia
Klebsiella pneumoniae
Odds Ratio
Therapeutics
Enterobacter
Mortality
Septic Shock
Multicenter Studies
Intensive Care Units
Neoplasms
Transplantation
Alleles

Keywords

  • Carbapenem-resistant Enterobacteriaceae
  • Clinical outcomes
  • Molecular epidemiology
  • Resistance mechanisms

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Multicenter clinical and molecular epidemiological analysis of bacteremia due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States. / Satlin, Michael J.; Chen, Liang; Patel, Gopi; Gomez-Simmonds, Angela; Weston, Gregory D.; Kim, Angela C.; Seo, Susan K.; Rosenthal, Marnie E.; Sperber, Steven J.; Jenkins, Stephen G.; Hamula, Camille L.; Uhlemann, Anne Catrin; Levi, Michael H.; Fries, Bettina C.; Tang, Yi Wei; Juretschko, Stefan; Rojtman, Albert D.; Hong, Tao; Mathema, Barun; Jacobs, Michael R.; Walsh, Thomas J.; Bonomo, Robert A.; Kreiswirth, Barry N.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 4, e02349-16, 01.04.2017.

Research output: Contribution to journalArticle

Satlin, MJ, Chen, L, Patel, G, Gomez-Simmonds, A, Weston, GD, Kim, AC, Seo, SK, Rosenthal, ME, Sperber, SJ, Jenkins, SG, Hamula, CL, Uhlemann, AC, Levi, MH, Fries, BC, Tang, YW, Juretschko, S, Rojtman, AD, Hong, T, Mathema, B, Jacobs, MR, Walsh, TJ, Bonomo, RA & Kreiswirth, BN 2017, 'Multicenter clinical and molecular epidemiological analysis of bacteremia due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States', Antimicrobial Agents and Chemotherapy, vol. 61, no. 4, e02349-16. https://doi.org/10.1128/AAC.02349-16
Satlin, Michael J. ; Chen, Liang ; Patel, Gopi ; Gomez-Simmonds, Angela ; Weston, Gregory D. ; Kim, Angela C. ; Seo, Susan K. ; Rosenthal, Marnie E. ; Sperber, Steven J. ; Jenkins, Stephen G. ; Hamula, Camille L. ; Uhlemann, Anne Catrin ; Levi, Michael H. ; Fries, Bettina C. ; Tang, Yi Wei ; Juretschko, Stefan ; Rojtman, Albert D. ; Hong, Tao ; Mathema, Barun ; Jacobs, Michael R. ; Walsh, Thomas J. ; Bonomo, Robert A. ; Kreiswirth, Barry N. / Multicenter clinical and molecular epidemiological analysis of bacteremia due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 4.
@article{a3ddb62a124742d0b73d482b4d6631d0,
title = "Multicenter clinical and molecular epidemiological analysis of bacteremia due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States",
abstract = "Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (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 among Enterobacteriaceae bloodstream 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 among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7{\%}, 2.2{\%}, and 0.1{\%}, respectively. Ninety percent of CRE were K. pneumoniae and 92{\%} produced K. pneumoniae carbapenemase (KPC-3, 48{\%}; KPC-2, 44{\%}). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93{\%} of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42{\%} of KPC-3-Kp had 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-Kp bacteremia (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.",
keywords = "Carbapenem-resistant Enterobacteriaceae, Clinical outcomes, Molecular epidemiology, Resistance mechanisms",
author = "Satlin, {Michael J.} and Liang Chen and Gopi Patel and Angela Gomez-Simmonds and Weston, {Gregory D.} and Kim, {Angela C.} and Seo, {Susan K.} and Rosenthal, {Marnie E.} and Sperber, {Steven J.} and Jenkins, {Stephen G.} and Hamula, {Camille L.} and Uhlemann, {Anne Catrin} and Levi, {Michael H.} and Fries, {Bettina C.} and Tang, {Yi Wei} and Stefan Juretschko and Rojtman, {Albert D.} and Tao Hong and Barun Mathema and Jacobs, {Michael R.} and Walsh, {Thomas J.} and Bonomo, {Robert A.} and Kreiswirth, {Barry N.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1128/AAC.02349-16",
language = "English (US)",
volume = "61",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Multicenter clinical and molecular epidemiological analysis of bacteremia due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States

AU - Satlin, Michael J.

AU - Chen, Liang

AU - Patel, Gopi

AU - Gomez-Simmonds, Angela

AU - Weston, Gregory D.

AU - Kim, Angela C.

AU - Seo, Susan K.

AU - Rosenthal, Marnie E.

AU - Sperber, Steven J.

AU - Jenkins, Stephen G.

AU - Hamula, Camille L.

AU - Uhlemann, Anne Catrin

AU - Levi, Michael H.

AU - Fries, Bettina C.

AU - Tang, Yi Wei

AU - Juretschko, Stefan

AU - Rojtman, Albert D.

AU - Hong, Tao

AU - Mathema, Barun

AU - Jacobs, Michael R.

AU - Walsh, Thomas J.

AU - Bonomo, Robert A.

AU - Kreiswirth, Barry N.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (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 among Enterobacteriaceae bloodstream 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 among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had 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-Kp bacteremia (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.

AB - Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (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 among Enterobacteriaceae bloodstream 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 among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had 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-Kp bacteremia (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.

KW - Carbapenem-resistant Enterobacteriaceae

KW - Clinical outcomes

KW - Molecular epidemiology

KW - Resistance mechanisms

UR - http://www.scopus.com/inward/record.url?scp=85016998555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016998555&partnerID=8YFLogxK

U2 - 10.1128/AAC.02349-16

DO - 10.1128/AAC.02349-16

M3 - Article

C2 - 28167547

AN - SCOPUS:85016998555

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 4

M1 - e02349-16

ER -