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
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.
N1 - Funding Information:
M. J. Satlin and B. N. Kreiswirth have received research grants from Allergan. A.-C. Uhlemann has received research grants from Merck. T. J. Walsh has received research grants from Allergan, Medicines Company, and Merck and serves as an advisor to Allergan and Pfizer. This work was partially supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (K23 AI114994 to M.J.S., R21 AI117338 to L.C., R01 AI090155 to B.N.K., and R01 AI116939 to A.-C.U.).
Publisher Copyright:
© 2017 American Society for Microbiology. All Rights Reserved.
PY - 2017/4
Y1 - 2017/4
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
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U2 - 10.1128/AAC.02349-16
DO - 10.1128/AAC.02349-16
M3 - Article
C2 - 28167547
AN - SCOPUS:85016998555
SN - 0066-4804
VL - 61
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 4
M1 - e02349-16
ER -