Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Post-Transplant Events

Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality

Bone Marrow Transplantation volume 40, pages 63–70 (2007)Cite this article

Abstract

Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.6%) developed BSI. Of the 185 isolates, 68% were Gram-positive cocci, 21% were Gram-negative bacilli (GNR) and 11% were fungi. Type of allogeneic HSCT was an independent risk factor for BSI (hazard ratio (HR) 3.26, 95% confidence interval (CI) 1.50, 7.07, P=0.01), as was the degree of HLA matching (HR 1.84, 95% CI 1.00, 3.37, P=0.05). BSI was a significant independent predictor of mortality after HSCT (HR 1.79, 95% CI 1.18, 2.73, P=0.007), after adjusting for acute graft-versus-host disease (GVHD) and allogeneic HSCT (both predicting death ⩽3 months after HSCT). In contrast to the effects of acute GVHD and allogeneic HSCT, the effect of BSI was evident throughout the post-HSCT period. GNR BSI and vancomycin-resistant enterococcal BSI also were significantly associated with death. We concluded that BSI is a common complication of HSCT associated with increased mortality throughout the post-HSCT period.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Williamson EC, Millar MR, Steward CG, Cornish JM, Foot AB, Oakhill A et al. Infections in adults undergoing unrelated donor bone marrow transplantation. Br J Haematol 1999; 104: 560–568.

    Article  CAS  Google Scholar 

  2. Ninin E, Milpied N, Moreau P, Andre-Richet B, Morineau N, Mahe B et al. Longitudinal study of bacterial, viral, and fungal infections in adult recipients of bone marrow transplants. Clin Infect Dis 2001; 33: 41–47.

    Article  CAS  Google Scholar 

  3. Engels EA, Ellis CA, Supran SE, Schmid CH, Barza M, Schenkein DP et al. Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk. Clin Infect Dis 1999; 28: 256–266.

    Article  CAS  Google Scholar 

  4. 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 

  5. Lenssen P, Bruemmer BA, Bowden RA, Gooley T, Aker SN, Mattson D . Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation. Am J Clin Nutr 1998; 67: 927–933.

    Article  CAS  Google Scholar 

  6. Sparrelid E, Hagglund H, Remberger M, Ringden O, Lonnqvist B, Ljungman P et al. Bacteraemia 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 

  7. Busca A, Saroglia EM, Giacchino M, Vai S, Vassallo E, Fagioli F et al. Analysis of early infectious complications in pediatric patients undergoing bone marrow transplantation. Support Care Cancer 1999; 7: 253–259.

    Article  CAS  Google Scholar 

  8. Barton T, Collis T, Stadtmauer E, Schuster M . Infectious complications the year after autologous bone marrow transplantation or peripheral stem cell transplantation for treatment of breast cancer. Clin Infect Dis 2001; 32: 391–395.

    Article  CAS  Google Scholar 

  9. Kersun LS, Propert KJ, Lautenbach E, Bunin N, Demichele A . Early bacteremia in pediatric hematopoietic stem cell transplant patients on oral antibiotic prophylaxis. Pediatr Blood Cancer 2005; 45: 162–169.

    Article  Google Scholar 

  10. 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 

  11. Winston DJ, Schiffman G, Wang DC, Feig SA, Lin CH, Marso EL et al. Pneumococcal infections after human bone-marrow transplantation. Ann Intern Med 1979; 91: 835–841.

    Article  CAS  Google Scholar 

  12. Elishoov H, Or R, Strauss N, Engelhard D . Nosocomial colonization, septicemia, and Hickman/Broviac catheter-related infections in bone marrow transplant recipients. A 5-year prospective study. Medicine 1998; 77: 83–101.

    Article  CAS  Google Scholar 

  13. Romano V, Castagnola E, Dallorso S, Lanino E, Calvi A, Silvestro S et al. Bloodstream infections can develop late (after day 100) and/or in the absence of neutropenia in children receiving allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 23: 271–275.

    Article  CAS  Google Scholar 

  14. Ortega M, Rovira M, Almela M, Marco F, de la Bellacasa JP, Martinez JA et al. Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000. Ann Hematol 2005; 84: 40–46.

    Article  Google Scholar 

  15. Tsakona CP, Khwaja A, Goldstone AH . Does treatment with haemopoietic growth factors affect the incidence of bacteraemia in adult lymphoma transplant recipients? Bone Marrow Transplant 1993; 11: 433–436.

    CAS  PubMed  Google Scholar 

  16. Yuen KY, Woo PC, Hui CH, Luk WK, Chen FE, Lie AK et al. Unique risk factors for bacteraemia in allogeneic bone marrow transplant recipients before and after engraftment. Bone Marrow Transplant 1998; 21: 1137–1143.

    Article  CAS  Google Scholar 

  17. Ruescher TJ, Sodeifi A, Scrivani SJ, Kaban LB, Sonis ST . The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies. Cancer 1998; 82: 2275–2281.

    Article  CAS  Google Scholar 

  18. Labarca JA, Leber AL, Kern VL, Territo MC, Brankovic LE, Bruckner DA et al. Outbreak of Stenotrophomonas maltophilia bacteremia in allogenic bone marrow transplant patients: role of severe neutropenia and mucositis. Clin Infect Dis 2000; 30: 195–197.

    Article  CAS  Google Scholar 

  19. Mitchell AE, Derrington P, Turner P, Hunt LP, Oakhill A, Marks DI . Gram-negative bacteraemia (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 

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

    Article  CAS  Google Scholar 

  21. Koc Y, Snydman DR, Schenkein DS, Miller KB . Vancomycin-resistant enterococcal infections in bone marrow transplant recipients. Bone Marrow Transplant 1998; 22: 207–209.

    Article  CAS  Google Scholar 

  22. DesJardin JA, Falagas ME, Ruthazer R, Griffith J, Wawrose D, Schenkein D et al. Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann Intern Med 1999; 131: 641–647.

    Article  CAS  Google Scholar 

  23. Miller KB, Roberts TF, Chan G, Schenkein DP, Lawrence D, Sprague K et al. A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease. Bone Marrow Transplant 2004; 33: 881–889.

    Article  CAS  Google Scholar 

  24. 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 

  25. Shoenfeld D . Partial residuals for the proportional hazards regression model. Biometrika 1982; 69: 239–241.

    Article  Google Scholar 

  26. Harrell Jr FE . %daspline.sas. Mayo Foundations for Medical Education and Research, Copyright 2006, 1991.

  27. Bergstralh E, Therneau T . %Schoen.sas. Mayo Foundations for Medical Education and Research, Copyright 2006 2002.

  28. Allison PD . Survival Analysis Using SAS(TM): A Practical GuideEstimating Cox Regression Models with PROC PHREG. SAS Institute Inc.: Cary, NC, 1995.

    Google Scholar 

  29. Gordis L . More on risk: estimating the potential for prevention. In: Epidemiology. Elsevier Saunders: Philadelphia, 2004, pp 191–198.

    Google Scholar 

  30. Cometta A, Zinner S, deBock R, Calandra T, Gaya H, Klastersky J et al. Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob Agents Chemother 1995; 39: 445–452.

    Article  CAS  Google Scholar 

  31. De Pauw B, Donnelly J . Infections in the immunocompromised host: general principles. In: Mandell J, Bennett J, Dolin R (eds). Principles and Practice of Infectious Diseases, 5th edn. Churchill Livingstone: Philadelphia, 2000, pp 3079–3090.

    Google Scholar 

  32. 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 

  33. Ip MS, Yuen KY, Woo PC, Luk WK, Tsang KW, Lam WK et al. Risk factors for pulmonary tuberculosis in bone marrow transplant recipients. Am J Respir Crit Care Med 1998; 158: 1173–1177.

    Article  CAS  Google Scholar 

  34. Ochs L, Shu X, Miller J, Enright H, Wagner J, Filipovich A et al. Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients. Blood 1995; 86: 3979–3986.

    CAS  Google Scholar 

  35. Vergis EN, Hayden MK, Chow JW, Snydman DR, Zervos MJ, Linden PK et al. Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. A prospective multicenter study. Ann Intern Med 2001; 135: 484–492.

    Article  CAS  Google Scholar 

  36. DiazGranados CA, Jernigan JA . Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection. J Infect Dis 2005; 191: 588–595.

    Article  CAS  Google Scholar 

  37. Papanicolaou GA, Meyers BR, Meyers J, Mendelson MH, Lou W, Emre S et al. Nosocomial infections with vancomycin-resistant Enterococcus faecium in liver transplant recipients: risk factors for acquisition and mortality. Clin Infect Dis 1996; 23: 760–766.

    Article  CAS  Google Scholar 

  38. Pizzo P, Hathorn J, Hiemenz J, Browne M, Commers J, Cotton D et al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. New Engl J Med 1986; 315: 552–558.

    Article  CAS  Google Scholar 

  39. De Pauw B, Deresinski S, Feld R, Lane-Allman E, Donnelly J . Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. Ann Intern Med 1994; 120: 834–844.

    Article  CAS  Google Scholar 

  40. Cordonnier C, Herbrecht R, Luis Pico J, Gardembas M, Delmer A, Delain M et al. Cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile episodes in neutropenic patients: a comparative study. Clin Infect Dis 1997; 24: 41–51.

    Article  CAS  Google Scholar 

  41. Anonymous. From the Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Report of a consensus panel. J Infect Dis 1990; 161: 397–401.

    Article  Google Scholar 

  42. Hughes WT, Pizzo PA, Wade JC, Armstrong D, Webb CD, Young LS . Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Infectious Diseases Society of America and the Food and Drug Administration [comment]. Clin Infect Dis 1992; 15 (Suppl 1): S206–S215.

    Article  Google Scholar 

  43. Schots R, Trullemans F, Van Riet I, Kaufman L, Hafsia A, Meddeb B et al. The clinical impact of early gram-positive bacteremia and the use of vancomycin after allogeneic bone marrow transplantation. Transplantation 2000; 69: 1511–1514.

    Article  CAS  Google Scholar 

  44. Nucci M, Andrade F, Vigorito A, Trabasso P, Aranha JF, Maiolino A et al. Infectious complications in patients randomized to receive allogeneic bone marrow or peripheral blood transplantation. Transpl Infect Dis 2003; 5: 167–173.

    Article  CAS  Google Scholar 

  45. Daly A, McAfee S, Dey B, Colby C, Schulte L, Yeap B et al. Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transplant 2003; 9: 373–382.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Robin Ruthazer, MPH for her thoughtful comments on the statistical analysis and Dr Silvia Munoz-Price for her help with data extraction of the acute graft-versus-host data. These data were presented in part at the Infectious Disease Society of America Annual Meeting, 12–15 October 2006, Toronto, Canada. Dr Poutsiaka was supported in part by the National Center for Research Resources, National Institutes of Health K23RR020042-02.

Author information

Authors and Affiliations

  1. Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA

    D D Poutsiaka & D R Snydman

  2. Division of Clinical Care Research, Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA

    L L Price

  3. Tufts University School of Medicine, Boston, MA, USA

    A Ucuzian

  4. Division of Hematology and Oncology, Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA

    G W Chan & K B Miller

Authors
  1. D D Poutsiaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L L Price
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Ucuzian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G W Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K B Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D R Snydman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D D Poutsiaka.

Additional information

There are no conflicts of interest for any author.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Poutsiaka, D., Price, L., Ucuzian, A. et al. Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transplant 40, 63–70 (2007). https://doi.org/10.1038/sj.bmt.1705690

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705690

Keywords

This article is cited by

Search

Advanced search

Quick links