Skip to main content

Advertisement

SpringerLink
Log in

Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropenia

  • IM - ORIGINAL
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Patients with chemotherapy-induced febrile neutropenia (FN) are vulnerable to extended-spectrum b-lactamase-producing Enterobacteriaceae (ESBL-PE) infection. Early identification of patients suspected to have ESBL-PE infection for empirical carbapenem administration is crucial; nevertheless, risk factors for ESBL-PE causing septic shock remain unclear. We identify factors to predict ESBL-PE in septic shock patients with chemotherapy-induced FN. In this observational, prospectively collected registry-based study, consecutive adult chemotherapy-induced FN patients with septic shock who were admitted to the emergency department between June 2012 and June 2018 were enrolled. Clinical and laboratory data extracted from the septic shock registry were assessed to identify risk factors for ESBL-PE. Of 179 chemotherapy-induced FN septic shock patients, ESBL-PE is isolated in 23 (12.8%). ESBL-PE infection is frequently seen in patients with hepatobiliary cancer (17.4% vs. 4.5%, P = 0.037), leukemia (13.0% vs. 2.6%, P = 0.046), and those with profound neutropenia (defined as absolute neutrophil count < 100) (73.9% vs. 43.6%, P = 0.007) in contrast to those with lung cancer (0% vs. 14.7%, P = 0.048) and other solid cancer (0% vs. 19.2%, P = 0.016). Multivariate logistic regression reveals that profound neutropenia (adjusted OR 3.67; 95% CI 1.372–9.799; P = 0.010) is an independent risk factor for ESBL-PE infection after adjusting age, the presence of solid tumor, and the parameters of sepsis severity scores. ESBL-PE is rare (12.9%) in chemotherapy-induced FN patients with septic shock. Early empirical carbapenem therapy might be considered in chemotherapy-induced FN patients with profound neutropenia.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, Herrstedt J, Committee Esmo Guidelines (2016) Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol 27(suppl 5):v111–v118. https://doi.org/10.1093/annonc/mdw325

    Article  CAS  PubMed  Google Scholar 

  2. Rodriguez-Bano J, Pascual A (2008) Clinical significance of extended-spectrum beta-lactamases. Expert Rev Anti Infect Ther 6:671–683. https://doi.org/10.1586/14787210.6.5.671

    Article  CAS  PubMed  Google Scholar 

  3. Pitout JD, Laupland KB (2008) Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 8:159–166. https://doi.org/10.1016/S1473-3099(08)70041-0

    Article  CAS  PubMed  Google Scholar 

  4. van Duin D, Doi Y (2017) The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 8:460–469. https://doi.org/10.1080/21505594.2016.1222343

    Article  CAS  PubMed  Google Scholar 

  5. Palacios-Baena ZR, Gutierrez-Gutierrez B, Calbo E, Almirante B, Viale P, Oliver A, Pintado V, Gasch O, Martinez-Martinez L, Pitout J, Akova M, Pena C, Molina Gil-Bermejo J, Hernandez A, Venditti M, Prim N, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Giamarellou H, Almela M, Perez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Pano-Pardo JR, Torre-Cisneros J, Souli M, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodriguez-Bano J (2017) Empiric therapy with carbapenem-sparing regimens for bloodstream infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: results from the INCREMENT cohort. Clin Infect Dis 65:1615–1623. https://doi.org/10.1093/cid/cix606

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Lee CH, Chu FY, Hsieh CC, Hong MY, Chi CH, Ko WC, Lee CC (2017) A simple scoring algorithm predicting extended-spectrum beta-lactamase producers in adults with community-onset monomicrobial Enterobacteriaceae bacteremia: matters of frequent emergency department users. Medicine (Baltimore) 96:e6648. https://doi.org/10.1097/MD.0000000000006648

    Article  CAS  Google Scholar 

  7. Kim SJ, Park KH, Chung JW, Sung H, Choi SH, Choi SH (2014) Prevalence and impact of extended-spectrum beta-lactamase production on clinical outcomes in cancer patients with Enterobacter species bacteremia. Korean J Intern Med 29:637–646. https://doi.org/10.3904/kjim.2014.29.5.637

    Article  PubMed Central  PubMed  Google Scholar 

  8. Ha YE, Kang CI, Cha MK, Park SY, Wi YM, Chung DR, Peck KR, Lee NY, Song JH (2013) Epidemiology and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in patients with cancer. Int J Antimicrob Agents 42:403–409. https://doi.org/10.1016/j.ijantimicag.2013.07.018

    Article  CAS  PubMed  Google Scholar 

  9. Gudiol C, Calatayud L, Garcia-Vidal C, Lora-Tamayo J, Cisnal M, Duarte R, Arnan M, Marin M, Carratala J, Gudiol F (2010) Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother 65:333–341. https://doi.org/10.1093/jac/dkp411

    Article  CAS  PubMed  Google Scholar 

  10. Goodman KE, Lessler J, Cosgrove SE, Harris AD, Lautenbach E, Han JH, Milstone AM, Massey CJ, Tamma PD, Antibacterial Resistance Leadership Group (2016) A clinical decision tree to predict whether a bacteremic patient is infected with an extended-spectrum beta-lactamase-producing organism. Clin Infect Dis 63:896–903. https://doi.org/10.1093/cid/ciw425

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Lee JA, Kang CI, Joo EJ, Ha YE, Kang SJ, Park SY, Chung DR, Peck KR, Ko KS, Lee NY, Song JH (2011) Epidemiology and clinical features of community-onset bacteremia caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Microb Drug Resist 17:267–273. https://doi.org/10.1089/mdr.2010.0134

    Article  PubMed  Google Scholar 

  12. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 41:580–637. https://doi.org/10.1097/CCM.0b013e31827e83af

    Article  PubMed  Google Scholar 

  13. Casserly B, Phillips GS, Schorr C, Dellinger RP, Townsend SR, Osborn TM, Reinhart K, Selvakumar N, Levy MM (2015) Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 43:567–573. https://doi.org/10.1097/CCM.0000000000000742

    Article  CAS  PubMed  Google Scholar 

  14. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL, International Surviving Sepsis Campaign Guidelines Committee, American Association of Critical-Care Nurses, American College of Chest Physicians, American College of Emergency Physicians, Canadian Critical Care Society, European Society of Clinical Microbiology and Infectious Diseases, European Society of Intensive Care Medicine, European Respiratory Society, International Sepsis Forum, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Society of Critical Care Medicine, Society of Hospital Medicine, Surgical Infection Society, World Federation of Societies of Intensive and Critical Care Medicine (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36:296–327. https://doi.org/10.1097/01.CCM.0000298158.12101.41

    Article  Google Scholar 

  15. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 45:486–552. https://doi.org/10.1097/CCM.0000000000002255

    Article  PubMed  Google Scholar 

  16. Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO, American Society of Clinical Oncology (2015) Recommendations for the use of wbc growth factors: American society of clinical oncology clinical practice guideline update. J Clin Oncol 33:3199–3212. https://doi.org/10.1200/JCO.2015.62.3488

    Article  CAS  PubMed  Google Scholar 

  17. Wayne P (2009) Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: nineteeneth informational supplement. CLSI document M100-S19

  18. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Reller LB, Sexton DJ (2002) Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137:791–797

    Article  PubMed  Google Scholar 

  19. Cardoso T, Almeida M, Friedman ND, Aragao I, Costa-Pereira A, Sarmento AE, Azevedo L (2014) Classification of healthcare-associated infection: a systematic review 10 years after the first proposal. BMC Med 12:40. https://doi.org/10.1186/1741-7015-12-40

    Article  PubMed Central  PubMed  Google Scholar 

  20. Alevizakos M, Gaitanidis A, Andreatos N, Arunachalam K, Flokas ME, Mylonakis E (2017) Bloodstream infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae among patients with malignancy: a systematic review and meta-analysis. Int J Antimicrob Agents 50:657–663. https://doi.org/10.1016/j.ijantimicag.2017.07.003

    Article  CAS  PubMed  Google Scholar 

  21. Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A, Lemiale V, Seguin A, Darmon M, Schlemmer B, Azoulay E (2012) Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 40:43–49. https://doi.org/10.1097/CCM.0b013e31822b50c2

    Article  PubMed  Google Scholar 

  22. Marin M, Gudiol C, Garcia-Vidal C, Ardanuy C, Carratala J (2014) Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center. Medicine (Baltimore) 93:143–149. https://doi.org/10.1097/MD.0000000000000026

    Article  CAS  Google Scholar 

  23. Royo-Cebrecos C, Gudiol C, Garcia J, Tubau F, Laporte J, Ardanuy C, Antonio M, Marin M, Gornals JB, Carratala J (2017) Characteristics, aetiology, antimicrobial resistance and outcomes of bacteraemic cholangitis in patients with solid tumours: a prospective cohort study. J Infect 74:172–178. https://doi.org/10.1016/j.jinf.2016.10.008

    Article  CAS  PubMed  Google Scholar 

  24. Kim BN, Woo JH, Kim MN, Ryu J, Kim YS (2002) Clinical implications of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae bacteraemia. J Hosp Infect 52:99–106

    Article  PubMed  Google Scholar 

  25. Viscoli C (2016) Bloodstream infections: the peak of the iceberg. Virulence 7:248–251. https://doi.org/10.1080/21505594.2016.1152440

    Article  PubMed Central  PubMed  Google Scholar 

  26. Bodey GP, Buckley M, Sathe YS, Freireich EJ (1966) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 64:328–340

    Article  CAS  PubMed  Google Scholar 

  27. Menichetti F (2010) Infectious complications in neutropenic cancer patients. Intern Emerg Med 5(Suppl 1):S21–S25. https://doi.org/10.1007/s11739-010-0456-8

    Article  PubMed  Google Scholar 

  28. Rosa RG, Goldani LZ, dos Santos RP (2014) Risk factors for multidrug-resistant bacteremia in hospitalized cancer patients with febrile neutropenia: a cohort study. Am J Infect Control 42:74–76. https://doi.org/10.1016/j.ajic.2013.06.025

    Article  PubMed  Google Scholar 

  29. El-Mahallawy HA, El-Wakil M, Moneer MM, Shalaby L (2011) Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer. Pediatr Blood Cancer 57:283–288. https://doi.org/10.1002/pbc.22926

    Article  PubMed  Google Scholar 

  30. Lin JN, Chen YH, Chang LL, Lai CH, Lin HL, Lin HH (2011) Clinical characteristics and outcomes of patients with extended-spectrum beta-lactamase-producing bacteremias in the emergency department. Intern Emerg Med 6:547–555. https://doi.org/10.1007/s11739-011-0707-3

    Article  PubMed  Google Scholar 

  31. Trecarichi EM, Cauda R, Tumbarello M (2012) Detecting risk and predicting patient mortality in patients with extended-spectrum beta-lactamase-producing Enterobacteriaceae bloodstream infections. Future Microbiol 7:1173–1189. https://doi.org/10.2217/fmb.12.100

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Youn-Jung Kim and Sung Min Jung contributed equally to this study.

Authors and Affiliations

  1. Department of Emergency Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olimpic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea

    Youn-Jung Kim, Sung Min Jung, Seung Mok Ryoo, Chang Hwan Sohn, Dong-Woo Seo, Kyoung Soo Lim & Won Young Kim

  2. Department of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Jihoon Kang

  3. Department of Biomedical Informatics, School of Medicine, University of California San Diego, 9500 Gilman Drive #0728, La Jolla, San Diego, CA, 92093, USA

    Dong-Woo Seo

  4. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Jin Won Huh

  5. Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Sung-Han Kim

Authors
  1. Youn-Jung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung Min Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jihoon Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seung Mok Ryoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chang Hwan Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong-Woo Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyoung Soo Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jin Won Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sung-Han Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Won Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Won Young Kim.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to disclose or any funding.

Statement of human and animal rights

The institutional review board of Asan medical center approved the registry (study no.: 2015-1253). All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained before data collection.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (docx 44 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, YJ., Jung, S.M., Kang, J. et al. Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropenia. Intern Emerg Med 14, 433–440 (2019). https://doi.org/10.1007/s11739-018-02015-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-018-02015-x

Keywords

Search

Navigation