Research Article| Volume 78, ISSUE 2, P101-105, February 2019

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Risk factors for mortality among carbapenem-resistant enterobacteriaceae carriers with focus on immunosuppression

Published:October 09, 2018DOI:



      To identify risk factors for mortality in a cohort of carbapenem-resistant enterobacteriaceae (CRE) carriers, focusing on immunosuppression and other risk factors known at the time of CRE carriage detection.


      We prospectively followed all new and known CRE carriers admitted between June 2016 and June 2017 to a single tertiary center in Israel. Patients were included in the study after confirmation of the carrier state. Demographic and clinical data were documented on admission or CRE acquisition and patients were followed prospectively post-discharge until January 2018 or death. Risk factors for mortality known at the time of the first encounter with a CRE carrier were sought. Adjusted hazard ratios (HR) for mortality at end of follow-up with 95% confidence intervals (CI) were assessed using Cox regression analysis.


      A total of 115 patients were included in the analysis. During the study period, 66 (57.4%) patients died. Immunosuppression was associated with mortality (HR 1.95, CI 95% 1.12–3.44), adjusted to the Charlson co-morbidity score, functional status, chronic renal disease and Klebsiella pneumonia CRE, the latter three also significantly associated with mortality. CRE bacteremia occurred among 24 (20.9%) carriers during follow up, more frequently among immunosuppressed patients and was significantly associated with mortality at end of follow-up (p = 0.015).


      Immunosuppression is independently associated with mortality among CRE carriers, possibly related to CRE bacteremia that is frequent among these patients. Further research is needed on interventions to prevent deaths among CRE carriers.


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        • Yamamoto M
        • Pop-Vicas Aurora E
        Treatment for infections with carbapenem-resistant Enterobacteriaceae: what options do we still have?.
        Crit Care. 2014; 18: 229
        • Patel G
        • Huprikar S
        • Factor Stephanie H
        • Jenkins Stephen G
        • Calfee David P
        Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.
        Infect Control Hosp Epidemiol. 2008; 29: 1099-1106
        • Papadimitriou-Olivgeris M
        • Marangos M
        • Fligou F
        • Christofidou M
        • Bartzavali C
        • Anastassiou Evangelos D
        • et al.
        Risk factors for KPC-producing Klebsiella pneumoniae enteric colonization upon ICU admission.
        J Antimicrob Chemother. 2012; 67: 2976-2981
        • Wiener-Well Y
        • Rudensky B
        • Yinnon AM
        • Kopuit P
        • Schlesinger Y
        • Broide E
        • et al.
        Carriage rate of carbapenem-resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak.
        J Hosp Infect. 2010; 74: 344-349
        • Bhargava A
        • Hayakawa K
        • Silverman E
        • Haider S
        • Alluri Krishna C
        • Datla S
        • et al.
        Risk factors for colonization due to carbapenem-resistant Enterobacteriaceae among patients exposed to long-term acute care and acute care facilities.
        Infect Control Hosp Epidemiol. 2014; 35: 398-405
        • Swaminathan M
        • Sharma S
        • Poliansky Blash S
        • Patel G
        • Banach David B
        • Phillips M
        • et al.
        Prevalence and risk factors for acquisition of carbapenem-resistant Enterobacteriaceae in the setting of endemicity.
        Infect Control Hosp Epidemiol. 2013; 34: 809-817
        • Giannella M
        • Trecarichi EM
        • De Rosa FG
        • Del Bono V
        • Bassetti M
        • Lewis RE
        • et al.
        Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study.
        Clin Microbiol Infect. 2014; 20: 1357-1362
        • Schechner V
        • Kotlovsky T
        • Kazma M
        • Mishali H
        • Schwartz D
        • Navon-Venezia S
        • et al.
        Asymptomatic rectal carriage of blaKPC producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected?.
        Clin Microbiol Infect. 2013; 19: 451-456
        • Dickstein Y
        • Edelman R
        • Dror T
        • Hussein K
        • Bar-Lavie Y
        • Paul M
        Carbapenem-resistant Enterobacteriaceae colonization and infection in critically ill patients: a retrospective matched cohort comparison with non-carriers.
        J Hosp Infect. 2016; 94: 54-59
        • McConville Thomas H
        • Sullivan Sean B
        • Gomez-Simmonds A
        • Whittier S
        Uhlemann Anne-Catrin. Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study.
        PLoS One. 2017; 12e0186195
        • Cooley L
        • Dendle C
        • Wolf J
        • Teh BW
        • Chen SC
        • Boutlis C
        • et al.
        Consensus guidelines for diagnosis, prophylaxis and management of P neumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014.
        Intern Med J. 2014; 44: 1350-1363
        • Quan H
        • Li B
        • Couris Chantal M
        • Fushimi K
        • Graham P
        • Hider P
        • et al.
        Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.
        Am J Epidemiol. 2011; 173: 676-682
      1. Clinical and Laboratory Standards Institute. M100-S23 Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Third Informational Supplement. January 2013.

        • Schechner V
        • Straus-Robinson K
        • Schwartz D
        • Pfeffer I
        • Tarabeia J
        • Moskovich R
        • et al.
        Evaluation of PCR-based testing for surveillance of KPC-producing carbapenem-resistant members of the Enterobacteriaceae family.
        J Clin Microbiol. 2009; 47: 3261-3265
        • Ellington Matthew J
        • Kistler J
        • Livermore David M
        • Woodford N
        Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases.
        J Antimicrob Chemother. 2007; 59: 321-322
        • Cattaneo C
        • Di Blasi R
        • Skert C
        • Candoni A
        • Martino B
        • Di Renzo N
        • et al.
        Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria.
        Ann Hematol. 2018; 97: 1717-1726
        • Trecarichi Enrico M
        • Pagano L
        • Martino B
        • Candoni A
        • Di Blasi R
        • Nadali G
        • et al.
        Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey.
        Am J Hematol. 2016; 91: 1076-1081
        • Andria N
        • Henig O
        • Kotler O
        • Domchenko A
        • Oren I
        • Zuckerman T
        • et al.
        Mortality burden related to infection with carbapenem-resistant Gram-negative bacteria among haematological cancer patients: a retrospective cohort study.
        J Antimicrob Chemother. 2015; 70: 3146-3153
        • Satlin Michael J
        • Cohen N
        • Ma Kevin C
        • Gedrimaite Z
        • Soave R
        • Askin G
        • et al.
        Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies.
        J Infect. 2016; 73: 336-345
        • Tofas P
        • Skiada A
        • Angelopoulou M
        • Sipsas N
        • Pavlopoulou I
        • Tsaousi S
        • et al.
        Carbapenemase-producing Klebsiella pneumoniae bloodstream infections in neutropenic patients with haematological malignancies or aplastic anaemia: Analysis of 50 cases.
        Int J Antimicrob Agents. 2016; 47: 335-339
        • Bar-Yoseph H
        • Hussein K
        • Braun E
        • Paul M
        Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis.
        J Antimicrob Chemother. 2016; 71: 2729-2739
        • Saidel-Odes L
        • Polachek H
        • Peled N
        • Riesenberg K
        • Schlaeffer F
        • Trabelsi Y
        • et al.
        A randomized, double-blind, placebo-controlled trial of selective digestive decontamination using oral gentamicin and oral polymyxin E for eradication of carbapenem-resistant Klebsiella pneumoniae carriage.
        Infect Control Hosp Epidemiol. 2012; 33: 14-19
        • Millan B
        • Park H
        • Hotte N
        • Mathieu O
        • Burguiere P
        • Tompkins Thomas A
        • et al.
        Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent clostridium difficile infection.
        Clin Infect Dis. 2016; 62: 1479-1486