SpringerLink
Log in

Risk factors and clinical outcomes for carbapenem-resistant Enterobacteriaceae nosocomial infections

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

This study was aimed to determine the risk factors of Carbapenem-resistant Enterobacteriaceae (CRE) nosocomial infections and assess the clinical outcomes. A case-case–control design was used to compare two groups of case patients with control patients from March 2010 to November 2014 in China. Risk factors for the acquisition of CRE infections and clinical outcomes were analyzed by univariable and multivariable analysis. A total of 94 patients with CRE infections, 93 patients with Carbapenem-susceptible Enterobacteriaceae (CSE) infections, and 93 patients with organisms other than Enterobacteriaceae infections were enrolled in this study. Fifty-five isolates were detected as the carbapenemase gene. KPC-2 was the most common carbapenemase (65.5 %, 36/55), followed by NDM-1 (16.4 %, 9/55), IMP-4 (14.5 %, 8/55), NDM-5 (1.8 %, 1/55), and NDM-7 (1.8 %, 1/55). Multivariable analysis implicated previous use of third or fourth generation cephalosporins (odds ratio [OR], 4.557; 95 % confidence interval [CI], 1.971–10.539; P < 0.001) and carbapenems (OR, 4.058; 95 % CI, 1.753-9.397; P = 0.001) as independent risk factors associated with CRE infection. The in-hospital mortality of the CRE group was 57.4 %. In the population of CRE infection, presence of central venous catheters (OR, 4.464; 95 % CI, 1.332–14.925; P = 0.015) and receipt of immunosuppressors (OR, 7.246; 95 % CI, 1.217–43.478; P = 0.030) were independent risk factors for mortality. Appropriate definitive treatment (OR, 0.339; 95 % CI, 0.120–0.954; P = 0.040) was a protective factor for in-hospital death of CRE infection. Kaplan–Meier curves of the CRE group had the shortest survival time compared with the other two groups. Survival time of patients infected with Enterobacteriaceae with a high meropenem MIC (≥8 mg/L) was shorter than that of patients with a low meropenem MIC (2,4, and ≤ 1 mg/L). In conclusion, CRE nosocomial infections are associated with prior exposure to third or fourth generation cephalosporins and carbapenems. Patients infected with CRE had poor outcome and high mortality, especially high meropenem MIC (≥8 mg/L). Appropriate definitive treatment to CRE infections in the patient is essential.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Temkin E, Adler A, Lerner A, Carmeli Y (2014) Carbapenem-resistant Enterobacteriaceae: biology, epidemiology, and management. Ann NY Acad Sci 1323:22–42

    Article  CAS  PubMed  Google Scholar 

  2. Queenan AM, Bush K (2007) Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 20:440–458, Table of contents

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nordmann P, Cuzon G, Naas T (2009) The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 9:228–236

    Article  CAS  PubMed  Google Scholar 

  4. Doumith M, Ellington MJ, Livermore DM, Woodford N (2009) Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. J Antimicrob Chemother 63:659–667

    Article  CAS  PubMed  Google Scholar 

  5. Falagas ME, Tansarli GS, Karageorgopoulos DE, Vardakas KZ (2014) Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg Infect Dis 20:1170–1175

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gupta N, Limbago BM, Patel JB, Kallen AJ (2011) Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 53:60–67

    Article  PubMed  Google Scholar 

  7. Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP (2008) Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 29:1099–1106

    Article  PubMed  Google Scholar 

  8. Chen S, Feng W, Chen J et al (2014) Spread of carbapenemase-producing enterobacteria in a southwest hospital in China. Ann Clin Microbiol Antimicrob 13:42

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kumarasamy KK, Toleman MA, Walsh TR et al (2010) Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10:597–602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bogan C, Kaye KS, Chopra T et al (2014) Outcomes of carbapenem-resistant Enterobacteriaceae isolation: matched analysis. Am J Infect Control 42:612–620

    Article  PubMed  Google Scholar 

  11. Kofteridis DP, Valachis A, Dimopoulou D et al (2014) Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: a case-case–control study. J Infect Chemother 20:293–297

    Article  PubMed  Google Scholar 

  12. Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y (2008) Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 52:1028–1033

    Article  CAS  PubMed  Google Scholar 

  13. Vardakas KZ, Matthaiou DK, Falagas ME, Antypa E, Koteli A, Antoniadou E (2015) Characteristics, risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit. J Infect 70:592–599

    Article  PubMed  Google Scholar 

  14. Correa L, Martino MD, Siqueira I et al (2013) A hospital-based matched case–control study to identify clinical outcome and risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection. BMC Infect Dis 13:80

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jeong SJ, Yoon SS, Bae IK, Jeong SH, Kim JM, Lee K (2014) Risk factors for mortality in patients with bloodstream infections caused by carbapenem-resistant Pseudomonas aeruginosa: clinical impact of bacterial virulence and strains on outcome. Diagn Microbiol Infect Dis 80:130–135

    Article  PubMed  Google Scholar 

  16. Kritsotakis EI, Tsioutis C, Roumbelaki M, Christidou A, Gikas A (2011) Antibiotic use and the risk of carbapenem-resistant extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case–control study. J Antimicrob Chemother 66:1383–1391

    Article  CAS  PubMed  Google Scholar 

  17. Harris AD, Karchmer TB, Carmeli Y, Samore MH (2001) Methodological principles of case–control studies that analyzed risk factors for antibiotic resistance: a systematic review. Clin Infect Dis 32:1055–1061

    Article  CAS  PubMed  Google Scholar 

  18. Kaye KS, Harris AD, Samore M, Carmeli Y (2005) The case-case–control study design: addressing the limitations of risk factor studies for antimicrobial resistance. Infect Control Hosp Epidemiol 26:346–351

    Article  PubMed  Google Scholar 

  19. Schechner V, Temkin E, Harbarth S, Carmeli Y, Schwaber MJ (2013) Epidemiological interpretation of studies examining the effect of antibiotic usage on resistance. Clin Microbiol Rev 26:289–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wacholder S, McLaughlin JK, Silverman DT, Mandel JS (1992) Selection of controls in case–control studies. I. Principles. Am J Epidemiol 135:1019–1028

    CAS  PubMed  Google Scholar 

  21. Wacholder S, Silverman DT, McLaughlin JK, Mandel JS (1992) Selection of controls in case–control studies. II. Types of controls. Am J Epidemiol 135:1029–1041

    CAS  PubMed  Google Scholar 

  22. CLSI. Clinical and Laboratory Standards Institute (2014) Performance standards for antimicrobial testing: twentieth informational supplement, CLSI document. M100-S24. Wayne, PA

  23. Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36:309–332

    Article  PubMed  Google Scholar 

  24. Wang X, Li H, Zhao C et al (2014) Novel NDM-9 metallo-beta-lactamase identified from a ST107 Klebsiella pneumoniae strain isolated in China. Int J Antimicrob Agents 44:90–91

    Article  CAS  PubMed  Google Scholar 

  25. Yang Q, Wang H, Sun H, Chen H, Xu Y, Chen M (2010) Phenotypic and genotypic characterization of Enterobacteriaceae with decreased susceptibility to carbapenems: results from large hospital-based surveillance studies in China. Antimicrob Agents Chemother 54:573–577

    Article  CAS  PubMed  Google Scholar 

  26. Centers for Disease Control and Prevention (CDC) (2013) Vital signs: carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep 62:165–70

  27. Hawkey PM, **ong J, Ye H, Li H, M’Zali FH (2001) Occurrence of a new metallo-beta-lactamase IMP-4 carried on a conjugative plasmid in Citrobacter youngae from the People’s Republic of China. FEMS Microbiol Lett 194:53–57

    CAS  PubMed  Google Scholar 

  28. Wei ZQ, Du XX, Yu YS, Shen P, Chen YG, Li LJ (2007) Plasmid-mediated KPC-2 in a Klebsiella pneumoniae isolate from China. Antimicrob Agents Chemother 51:763–765

    Article  CAS  PubMed  Google Scholar 

  29. Yu YS, Du XX, Zhou ZH, Chen YG, Li LJ (2006) First isolation of blaIMI-2 in an Enterobacter cloacae clinical isolate from China. Antimicrob Agents Chemother 50:1610–1611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang X, Lou D, Xu Y et al (2013) First identification of coexistence of blaNDM-1 and blaCMY-42 among Escherichia coli ST167 clinical isolates. BMC Microbiol 13:282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang Q, Zhao CJ, Wang H et al (2013) Antimicrobial resistance of gram-negative bacilli isolated from 13 teaching hospitals across China. Zhonghua Yi Xue Za Zhi 93:1388–1396

    CAS  PubMed  Google Scholar 

  32. Ahn JY, Song JE, Kim MH et al (2014) Risk factors for the acquisition of carbapenem-resistant Escherichia coli at a tertiary care center in South Korea: a matched case–control study. Am J Infect Control 42:621–625

    Article  PubMed  Google Scholar 

  33. Teo J, Cai Y, Tang S et al (2012) Risk factors, molecular epidemiology and outcomes of ertapenem-resistant, carbapenem-susceptible Enterobacteriaceae: a case-case–control study. PLoS One 7:e34254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Qureshi ZA, Paterson DL, Potoski BA et al (2012) Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 56:2108–2113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Patel TS, Nagel JL (2015) Clinical outcomes of Enterobacteriaceae infections stratified by Carbapenem MICs. J Clin Microbiol 53:201–205

    Article  CAS  PubMed  Google Scholar 

  36. Daikos GL, Markogiannakis A (2011) Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems? Clin Microbiol Infect 17:1135–1141

    Article  CAS  PubMed  Google Scholar 

  37. Axel H, Stephan G (2014) Treatment of infections caused by carbapenem-resistant enterobacteriaceae. Curr Treat Options Infect Dis 4:425–438

    Google Scholar 

Download references

Acknowledgments

We thank Professor Fengxue Zhu and Doctor Zengli **ao from Intensive Care Unit of Peking University People’s Hospital for providing APACHE II scores.

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Peking University People’s Hospital, Bei**g, 100044, China

    Q. Wang, Y. Zhang, H. **an, H. Chen, X. Wang, R. Wang, C. Zhao & H. Wang

  2. Department of Infectious Diseases and Clinical Microbiology, Bei**g Chao-Yang Hospital of Capital Medical University, Bei**g, 150060, China

    X. Yao, Y. Liu, H. Li & B. Cao

Authors
  1. Q. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. X. Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. **an
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. X. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B. Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Wang.

Ethics declarations

Funding

This work was supported by the National Natural Science Foundation (81572036).

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Q., Zhang, Y., Yao, X. et al. Risk factors and clinical outcomes for carbapenem-resistant Enterobacteriaceae nosocomial infections. Eur J Clin Microbiol Infect Dis 35, 1679–1689 (2016). https://doi.org/10.1007/s10096-016-2710-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-016-2710-0

Keywords

Search

Navigation