Skip to main content

Advertisement

SpringerLink
Log in

Bloodstream infections with gram-negative organisms and the impact of multidrug resistance in patients with hematological malignancies

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Infections and especially blood stream infections (BSI) with gram-negative bacteria (GNB) represent a major threat for patients with hematological diseases undergoing chemotherapy and mainly contribute to morbidity and mortality. In this retrospective single-center study, we analyzed the impact of BSI with different gram-negative multidrug-resistant bacteria (MDRGN) compared to BSI with antibiotic susceptible gram-negative bacteria. Data of 109 patients with hematological malignancies and GNB BSI were analyzed with overall survival (OS) 30 days after BSI being the primary endpoint. BSI with non-fermentative gram-negative bacteria were found in 26.6% of all patients and 73.4% suffered from a BSI with an Enterobacteriaceae. Thirty-two of 109 patients suffered from BSI with MDRGN. Characteristics of MDRGN and non-MDRGN BSI patients did not differ besides the fact that significantly more patients received an immunosuppressive therapy in the MDRGN BSI group. OS (30 days after BSI) of patients with MDRGN BSI was significantly lower (85.6 vs. 55.9%; p < 0.001) compared to patients with non-MDRGN BSI. Patients with MDRGN BSI with non-fermentative pathogens had a worse OS after 30 days compared to MDRGN BSI with Enterobacteriaceae and the same holds true for non-MDRGN BSI. In multivariate analysis of MDRGN BSI, non-fermenters and ICU admission were independently associated with increased 30-day mortality. Our data demonstrate the negative impact of non-fermentative gram-negative pathogens causing BSI compared to Enterobacteriaceae in hematological patients and thereby underlining the heterogeneity of gram-negative BSI.

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
Fig. 2

Similar content being viewed by others

References

  1. Horasan ES, Ersoz G, Tombak A, Tiftik N, Kaya A (2011) Bloodstream infections and mortality-related factors in febrile neutropenic cancer patients. Med Sci Monit 17(5):CR304–CR309

    Article  Google Scholar 

  2. Klastersky J, Ameye L, Maertens J, Georgala A, Muanza F, Aoun M, Ferrant A, Rapoport B, Rolston K, Paesmans M (2007) Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents 30(Suppl 1):S51–S59. https://doi.org/10.1016/j.ijantimicag.2007.06.012

    Article  CAS  PubMed  Google Scholar 

  3. Collin BA, Leather HL, Wingard JR, Ramphal R (2001) Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis 33(7):947–953. https://doi.org/10.1086/322604

    Article  CAS  PubMed  Google Scholar 

  4. Nørgaard M, Larsson H, Pedersen G, Schønheyder HC, Sørensen HT (2006) Risk of bacteraemia and mortality in patients with haematological malignancies. Clin Microbiol Infect 12(3):217–223. https://doi.org/10.1111/j.1469-0691.2005.01298.x

    Article  PubMed  Google Scholar 

  5. Trecarichi EM, Tumbarello M (2014) Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer. Current epidemiology and clinical impact. Curr Opin Infect Dis 27(2):200–210. https://doi.org/10.1097/QCO.0000000000000038

    Article  CAS  PubMed  Google Scholar 

  6. Trecarichi EM, Pagano L, Candoni A, Pastore D, Cattaneo C, Fanci R, Nosari A, Caira M, Spadea A, Busca A, Vianelli N, Tumbarello M, HeMABIS Registry—SEIFEM Group, Italy (2015) Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies. An Italian multicentre prospective survey. Clin Microbiol Infect 21(4):337–343. https://doi.org/10.1016/j.cmi.2014.11.022

    Article  CAS  PubMed  Google Scholar 

  7. Baker TM, Satlin MJ (2016) The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies. Leuk Lymphoma 57(10):2245–2258. https://doi.org/10.1080/10428194.2016.1193859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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(2):333–341. https://doi.org/10.1093/jac/dkp411

    Article  CAS  PubMed  Google Scholar 

  9. Kang C-I, Chung DR, Ko KS et al (2012) Risk factors for infection and treatment outcome of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in patients with hematologic malignancy. Ann Hematol 91(1):115–121. https://doi.org/10.1007/s00277-011-1247-7

    Article  CAS  PubMed  Google Scholar 

  10. Cornejo-Juárez P, Vilar-Compte D, Pérez-Jiménez C, Ñamendys-Silva SA, Sandoval-Hernández S, Volkow-Fernández P (2015) The impact of hospital-acquired infections with multidrug-resistant bacteria in an oncology intensive care unit. Int J Infect Dis 31:31–34. https://doi.org/10.1016/j.ijid.2014.12.022

    Article  PubMed  Google Scholar 

  11. Kim S-H, Kwon J-C, Choi S-M, Lee DG, Park SH, Choi JH, Yoo JH, Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Min WS (2013) Escherichia coli and Klebsiella pneumoniae bacteremia in patients with neutropenic fever. Factors associated with extended-spectrum β-lactamase production and its impact on outcome. Ann Hematol 92(4):533–541. https://doi.org/10.1007/s00277-012-1631-y

    Article  CAS  PubMed  Google Scholar 

  12. Ha YE, Kang C-I, 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 β-lactamase-producing Escherichia coli in patients with cancer. Int J Antimicrob Agents 42(5):403–409. https://doi.org/10.1016/j.ijantimicag.2013.07.018

    Article  CAS  PubMed  Google Scholar 

  13. Metan G, Demiraslan H, Kaynar LG, Zararsız G, Alp E, Eser B (2013) Factors influencing the early mortality in haematological malignancy patients with nosocomial Gram negative bacilli bacteraemia. A retrospective analysis of 154 cases. Braz J Infect Dis 17(2):143–149. https://doi.org/10.1016/j.bjid.2012.09.010

    Article  PubMed  Google Scholar 

  14. Trecarichi EM, Pagano L, Martino B, Candoni A, di Blasi R, Nadali G, Fianchi L, Delia M, Sica S, Perriello V, Busca A, Aversa F, Fanci R, Melillo L, Lessi F, del Principe MI, Cattaneo C, Tumbarello M, for the Haematologic Malignancies Associated Bloodstream Infections Surveillance (HEMABIS) registry - Sorveglianza Epidemiologica Infezioni Funginein Emopatie Maligne(SEIFEM) group, Italy (2016) Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients. Clinical impact of carbapenem resistance in a multicentre prospective survey. Am J Hematol 91(11):1076–1081. https://doi.org/10.1002/ajh.24489

    Article  CAS  PubMed  Google Scholar 

  15. Klastersky J, de NJ, Rolston K et al (2016) Management of febrile neutropenia. Ann Oncol 27(suppl 5):v111–v118. https://doi.org/10.1093/annonc/mdw325

    Article  CAS  PubMed  Google Scholar 

  16. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies. Development and validation. J Chronic Dis 40(5):373–383

    Article  CAS  Google Scholar 

  17. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173(6):676–682. https://doi.org/10.1093/aje/kwq433

    Article  PubMed  Google Scholar 

  18. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE). v4.03 2010. Retrieved from www.evs.nci.nih.gov. Accessed 18 Apr 2017

  19. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18(3):268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x

    Article  CAS  PubMed  Google Scholar 

  20. (2012) Hygienemassnahmen bei Infektionen oder Besiedlung mit multiresistenten gramnegativen Stabchen. Empfehlung der Kommission fur Kranken-haushygiene und Infektionspravention (KRINKO) beim Robert Koch-Institut (RKI) (Hygiene measures for infection or colonization with multidrug-resistant gram-negative bacilli Commission recommendation for hospital hygiene and infection prevention (KRINKO) at the Robert Koch Institute (RKI)). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 55(10): 1311–1354. https://doi.org/10.1007/s00103-012-1549-5

  21. Reinheimer C, Kempf VAJ, Gottig S et al. (2016) Multidrug-resistant organisms detected in refugee patients admitted to a university hospital, Germany June-December 2015. Euro Surveil 21(2). https://doi.org/10.2807/1560-7917.ES.2016.21.2.30110

  22. Doyle D, Peirano G, Lascols C, Lloyd T, Church DL, Pitout JDD (2012) Laboratory detection of Enterobacteriaceae that produce carbapenemases. J Clin Microbiol 50(12):3877–3880. https://doi.org/10.1128/JCM.02117-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Higgins PG, Dammhayn C, Hackel M, Seifert H (2010) Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 65(2):233–238. https://doi.org/10.1093/jac/dkp428

    Article  CAS  PubMed  Google Scholar 

  24. Brooke JS (2012) Stenotrophomonas maltophilia. An emerging global opportunistic pathogen. Clin Microbiol Rev 25(1):2–41. https://doi.org/10.1128/CMR.00019-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. European Centre for Disease Prevention and Control (2017) Antimicrobial resistance surveillance in Europe´2015. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 26. https://doi.org/10.2900/6928

  26. Averbuch D, Tridello G, Hoek J et al (2017) Antimicrobial resistance in Gram-negative rods causing bacteremia in hematopoietic stem cell transplant patients. Intercontinental prospective study of Infectious Diseases Working Party of the European Bone Marrow Transplantation group. Clin Inf Dis. https://doi.org/10.1093/cid/cix646

    Article  Google Scholar 

  27. Averbuch D, Avaky C, Harit M, Stepensky P, Fried I, Ben-Ami T, Temper V, Peled Y, Troen H, Masarwa R, Abu Ahmad W, Weintraub M, Revel-Vilk S, Engelhard D (2017) Non-fermentative Gram-negative rods bacteremia in children with cancer. A 14-year single-center experience. Infection 45(3):327–334. https://doi.org/10.1007/s15010-017-0988-1

    Article  CAS  PubMed  Google Scholar 

  28. Satlin MJ, Cohen N, Ma KC, Gedrimaite Z, Soave R, Askin G, Chen L, Kreiswirth BN, Walsh TJ, Seo SK (2016) Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies. J Inf Secur 73(4):336–345. https://doi.org/10.1016/j.jinf.2016.07.002

    Article  Google Scholar 

  29. Cattaneo C, Zappasodi P, Mancini V, Annaloro C, Pavesi F, Skert C, Ferrario A, Todisco E, Saccà V, Verga L, Passi A, da Vià M, Ferrari S, Mometto G, Petullà M, Nosari A, Rossi G (2016) Emerging resistant bacteria strains in bloodstream infections of acute leukaemia patients. Results of a prospective study by the rete Ematologica Lombarda (Rel). Ann Hematol 95(12):1955–1963. https://doi.org/10.1007/s00277-016-2815-7

    Article  PubMed  Google Scholar 

  30. Caselli D, Cesaro S, Ziino O, Zanazzo G, Manicone R, Livadiotti S, Cellini M, Frenos S, Milano GM, Cappelli B, Licciardello M, Beretta C, Arico M, Castagnola E, for the “Infection Study Group” of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) (2010) Multidrug resistant Pseudomonas aeruginosa infection in children undergoing chemotherapy and hematopoietic stem cell transplantation. Haematologica 95(9):1612–1615. https://doi.org/10.3324/haematol.2009.020867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lin MY, Weinstein RA, Hota B (2008) Delay of active antimicrobial therapy and mortality among patients with bacteremia. Impact of severe neutropenia. Antimicrob Agents Chemother 52(9):3188–3194. https://doi.org/10.1128/AAC.01553-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank all technicians and physicians involved in pre-transplant procedures, allo-HSCT and care of patients as an outpatient. The work of VAJK was supported by a grant of the Deutsche Forschungsgemeninschaft (DFG Research Unit 2251).

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany

    Sebastian Scheich, Sarah Weber, Hubert Serve & Björn Steffen

  2. University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany

    Sebastian Scheich, Sarah Weber, Claudia Reinheimer, Thomas A. Wichelhaus, Michael Hogardt, Volkhard A. J. Kempf, Johanna Kessel, Hubert Serve & Björn Steffen

  3. Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany

    Claudia Reinheimer, Thomas A. Wichelhaus, Michael Hogardt & Volkhard A. J. Kempf

  4. Department of Medicine, Infectious Diseases Unit, University Hospital Frankfurt, Frankfurt am Main, Germany

    Johanna Kessel

Authors
  1. Sebastian Scheich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudia Reinheimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas A. Wichelhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Hogardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Volkhard A. J. Kempf
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Johanna Kessel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hubert Serve
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Björn Steffen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SS and BS designed the study. SS and SW collected data. SS, SW, CR, TAW, MH, VAJK, JK, HS and BS interpreted the data. SS, BS and SW wrote the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Sebastian Scheich.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scheich, S., Weber, S., Reinheimer, C. et al. Bloodstream infections with gram-negative organisms and the impact of multidrug resistance in patients with hematological malignancies. Ann Hematol 97, 2225–2234 (2018). https://doi.org/10.1007/s00277-018-3423-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-018-3423-5

Keywords

Search

Navigation