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Infections

Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients

Bone Marrow Transplantation volume 49, pages 824–830 (2014)Cite this article

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Abstract

We conducted an observational study to assess the etiology, clinical features and outcomes of bloodstream infection (BSI) in 172 hematopoietic SCT (HCST) recipients. One hundred episodes of BSI in the pre-engraftment period (early onset) were compared with 89 episodes in the post-engraftment phase (late onset). More patients with late-onset BSI received an allogeneic HSCT, had GVHD and had received corticosteroids, whereas patients with early-onset BSI were more likely to have neutropenia, severe mucositis and a central venous catheter (CVC) in place. CVC was the most frequent site of infection, followed by an endogenous source. Pneumonia and gastrointestinal infection were particularly frequent in late-onset BSI, whereas mucositis was more frequent in the early-onset group. Gram-positive organisms predominated over Gram negatives. Streptococcus pneumoniae was more frequent in patients with late-onset BSI. Patients with late-onset BSI presented worse outcomes regarding septic shock, intensive care unit admission and early and overall case-fatality rates. Early-onset BSI was mainly related to the presence of neutropenia, mucositis and CVC, whereas late-onset BSI mainly affected severely immunosuppressed allogeneic HSCT recipients with GVHD and corticosteroids. Late-onset BSI caused high case-fatality rates. BSI due to S. pneumoniae was especially frequent late after transplantation. The development of better vaccination strategies is needed.

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References

  1. Mikulska M, Del Bono V, Raiola AM, Bruno B, Gualandi F, Occhini D et al. Bloodstream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant 2009; 15: 47–53.

    Article  CAS  Google Scholar 

  2. Almyroudis NG, Fuller A, Jakubowski A, Sepkowitz K, Jaffe D, Small TN et al. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2005; 7: 11–17.

    Article  CAS  Google Scholar 

  3. Poutsiaka DD, Price LL, Ucuzian A, Chan GW, Miller KB, Snydman DR . Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transplant 2007; 40: 63–70.

    Article  CAS  Google Scholar 

  4. Liu CY, Lai YC, Huang LJ, Yang YW, Chen TL, Hsiao LT et al. Impact of bloodstream infections on outcome and the influence of prophylactic oral antibiotic regimens in allogeneic hematopoietic SCT recipients. Bone Marrow Transplant 2011; 46: 1231–1239.

    Article  CAS  Google Scholar 

  5. Dettenkofer M, Ebner W, Bertz H, Babikir R, Finke J, Franf U et al. Surveillance of nosocomial infections in adult recipients of allogeneic and autologous bone marrow and peripheral blood stem-cell transplantation. Bone Marrow Transplant 2003; 31: 795–801.

    Article  CAS  Google Scholar 

  6. Yuen KY, Woo PCY, HUi CH, Luk WK, Chen FE, Lie AKW et al. Unique risk factors for bacteremia in allogeneic bone marrow transplant recipients before and after engraftment. Bone Marrow Transplant 1998; 21: 1137–1143.

    Article  CAS  Google Scholar 

  7. Collin BA, Leather HL, Wingard JR, Ramphal R . Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant recipients. Clin Infect Dis 2001; 33: 947–953.

    Article  CAS  Google Scholar 

  8. Garnica M, Maiolino A, Nucci M . Factors associated with bacteremia due to multidrug-resistant Gram-negative bacilli in hematopoietic stem cell transplant recipients. Braz J Med Biol Res 2009; 42: 289–293.

    Article  CAS  Google Scholar 

  9. Mitchell AE, Derrington P, Turner P, Hunt LP, Oakhill A, Marks DI . Gram-negative bacteremia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome. Bone Marrow Transplant 2004; 33: 303–310.

    Article  CAS  Google Scholar 

  10. Sparrelid E, Hägglund H, Remberger M, Ringdén O, Lönnqvist B, Ljungman P et al. Bacteremia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection. Bone Marrow Transplant 1998; 22: 795–800.

    Article  CAS  Google Scholar 

  11. Zinner SH . Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on Gram-positive and resistant bacteria. Clin Infect Dis 1999; 29: 490–494.

    Article  CAS  Google Scholar 

  12. Gudiol C, Bodro M, Simonetti A, Tubau F, González-Barca E, Cisnal M et al. Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect 2013; 19: 474–479.

    Article  CAS  Google Scholar 

  13. Mikulska M, del Bono V, Bruzzi P, Raiola AM, Gualandi F, van Lint MT et al. Mortality after bloodstream infections in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Infection 2012; 40: 271–278.

    Article  CAS  Google Scholar 

  14. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  15. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  Google Scholar 

  16. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268–281.

    Article  CAS  Google Scholar 

  17. Miller AN, Glode A, Hogan KR, Schaub C, Kramer C, Stuart RK et al. Efficacy and safety of ciprofloxacin for prophylaxis of polyomavirus BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant 2011; 17: 1176–1181.

    Article  CAS  Google Scholar 

  18. Sánchez-Ortega I, Patiño B, Arnan M, Peralta T, Parody R, Gudiol C et al. Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole vs itraconazole in allogeneic blood and marrow transplantation. Bone Marrow Transplant 2011; 46: 733–739.

    Article  Google Scholar 

  19. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing.(20th Informational Supplement. CLSI document M100-S20) Clinical and Laboratory Standards Institute: (Wayne, PA, USA, 2010).

  20. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, 8th edn. (Approved Standard M07-A8) (CLSI: Wayne, PA, USA, 2009).

  21. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twentieth Informational Supplement. (CLSI document M100-S22) (CLSI: Wayne, PA, USA, 2012).

  22. Hosmer DW, Lemeshow S . Logistic regression: variable selection. In: Hosmer DW, Lemeshow S (eds). Applied Logistic Regression, 2nd edn. John Willey & Sons: New York, NY, USA, 2000.

    Chapter  Google Scholar 

  23. Poutsiaka DD, Munson D, Price LL, Chan GW, Snydman DR . Blood stream infection (BSI) and acute graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT) are associated. Bone Marrow Transplant 2011; 46: 300–307.

    Article  CAS  Google Scholar 

  24. Sosa R, Weiden PL, Storb R, Syrotuck J, Thomas ED . Granulocyte function in human allogeneic marrow graft recipients. Exp Hematol 1980; 8: 1183–1189.

    CAS  PubMed  Google Scholar 

  25. Lum LG . The kinetics of immune reconstitution after bone marrow transplantation. Blood 1987; 69: 369–380.

    CAS  PubMed  Google Scholar 

  26. Cupps TR, Fauci AS . Corticosteroid-mediated immunoregulation in man. Immunol Rev 1982; 65: 133–155.

    Article  CAS  Google Scholar 

  27. Ariza-Heredia EJ, Nesher L, Chemaly RF . Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett 2013; 342: 1–8.

    Article  Google Scholar 

  28. Oliveira AL, de Souza M, Carvalho-Dias VM, Ruiz MA, Silla L, Tanaka PY et al. Epidemiology of bacteremia and factors associates with multidrug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2007; 39: 775–781.

    Article  CAS  Google Scholar 

  29. Kumar D, Humar A, Plevneshi A, Siegal D, Franke N, Green K et al. Invasive pneumococcal disease in adult hematopoietic stem cell transplant recicpients: a decade of prospective population-based surveillance. Bone Marrow Transplant 2008; 41: 743–747.

    Article  CAS  Google Scholar 

  30. Kulkarni S, Powles R, Treleaven J, Riley U, Singhal S, Horton C et al. Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants. Blood 2000; 95: 3683–3686.

    CAS  PubMed  Google Scholar 

  31. Youseef S, Rodríguez G, Rolston KV, Champlin RE, Raad I, Safdar A . Streptococcus pneumoniae infections in 47 hematopoietic stem cell transplantation recipients: clinical characteristics of infections and vaccine-breakthrough infections, 1989-2005. Medicine (Baltimore) 2007; 86: 69–77.

    Article  Google Scholar 

  32. Engelhard D, Cordonnier C, Shaw PJ, Parkalli T, Guenther C, Martino R et al. Early and late invasive pneumococcal infection following stem cell trasnplantation: a European Bone Marrow Transplantation survey. Br J Hematol 2002; 117: 444–450 .

    Article  Google Scholar 

  33. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15: 1143–1238.

    Article  CAS  Google Scholar 

  34. Song JH . Advances in pneumococcal antibiotic resistance. Expert Rev Respir Med 2013; 7: 491–498.

    Article  CAS  Google Scholar 

  35. Ljungman P, Cordonnier C, Einsele H, Englund J, Machado CM, Storek J et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant 2009; 44: 521–526.

    Article  CAS  Google Scholar 

  36. Ljungman P, Small TN . Vaccination of SCT recipients. Bone Marrow Transplant 2011; 46: 621.

    Article  CAS  Google Scholar 

  37. Cordonnier C, Labopin M, Chesnel V, Ribaud P, Camara Rde L, Martino R et al. Immune response to the 23-valent polysaccharide pneumococcal vaccine (PPV23) after the 7-valent conjugate vaccine (PCV7) in allogeneic stem cell transplant (SCT) recipients: results of the EBMT IDWP01 trial. Vaccine 2010; 28: 2730–2734.

    Article  CAS  Google Scholar 

  38. Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD . The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998; 244: 379–386.

    Article  CAS  Google Scholar 

  39. Engelhard D, Elishoov H, Strauss N, Naparstek E, Nagler A, Simhon A et al. Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study. Transplantation 1996; 61: 430–434.

    Article  CAS  Google Scholar 

  40. Marron A, Carratalà J, González-Barca E, Fernández-Sevilla A, Alcalde F, Gudiol F . Serious complications of bacteremia caused by viridans streptococci in neutropenic patients with cancer. Clin Infect Dis 2000; 31: 1126–1130.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Infectious Diseases, Hospital Universitari de Bellvitge, Barcelona, Spain,

    C Gudiol, C Garcia-Vidal & J Carratalà

  2. REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain,

    C Gudiol, C Garcia-Vidal & J Carratalà

  3. Department of Haematology, Hospital Duran i Reynals, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain

    M Arnan, I Sánchez-Ortega, B Patiño & R Duarte

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  1. C Gudiol
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  2. C Garcia-Vidal
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Correspondence to C Gudiol or J Carratalà.

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Gudiol, C., Garcia-Vidal, C., Arnan, M. et al. Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients. Bone Marrow Transplant 49, 824–830 (2014). https://doi.org/10.1038/bmt.2014.37

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