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Published in: Annals of Hematology 11/2018

01-11-2018 | Original Article

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

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

Published in: Annals of Hematology | Issue 11/2018

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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.
Literature
1.
go back to reference 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–CR309CrossRef 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–CR309CrossRef
6.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
8.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
11.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
14.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
16.
go back to reference 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):373–383CrossRef 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):373–383CrossRef
17.
18.
go back to reference 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 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.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
20.
go back to reference (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 (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
25.
go back to reference 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 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.
go back to reference 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 CrossRef 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 CrossRef
27.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
29.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
30.
go back to reference 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 CrossRefPubMedPubMedCentral 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 CrossRefPubMedPubMedCentral
Metadata
Title
Bloodstream infections with gram-negative organisms and the impact of multidrug resistance in patients with hematological malignancies
Authors
Sebastian Scheich
Sarah Weber
Claudia Reinheimer
Thomas A. Wichelhaus
Michael Hogardt
Volkhard A. J. Kempf
Johanna Kessel
Hubert Serve
Björn Steffen
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 11/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3423-5

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