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:

Infections

Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study

Bone Marrow Transplantation volume 51, pages 1490–1495 (2016)Cite this article

Subjects

Abstract

We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9–62.2), which is 30-fold (95% CI 18–51; P<0.001) higher compared with persons without HSCT. Incidence was higher in allogeneic HSCT compared with autologous HSCT (70.0 vs 15.8 per 100 000 patients per year). Causative organisms were Streptococcus pneumoniae in 11 patients, Neisseria meningitidis in two and Streptococcus mitis in one patient. Mortality was 3 of 14 (21%) and 6 of 11 (55%) survivors had sequelae. Nine of 11 patients (82%) with pneumococcal meningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur.

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

Similar content being viewed by others

References

  1. Brouwer MC, Tunkel AR, van de Beek D . Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010; 23: 467–492.

    Article  CAS  Google Scholar 

  2. Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J . Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series. Lancet Neurol 2006; 5: 123–129.

    Article  Google Scholar 

  3. Khayr W, Haddad RY, Noor SA . Infections in hematological malignancies. Dis Mon 2012; 58: 239–249.

    Article  Google Scholar 

  4. Johnston BL, Conly JM . Immunization for bone marrow transplant recipients. Can J Infect Dis 2002; 13: 353–357.

    Article  Google Scholar 

  5. Socie G, Ritz J . Current issues in chronic graft-versus-host disease. Blood 2014; 124: 374–384.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Torda A, Chong Q, Lee A, Chen S, Dodds A, Greenwood M et al. Invasive pneumococcal disease following adult allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2014; 16: 751–759.

    Article  CAS  Google Scholar 

  8. de Almeida SM, Teive HA, Brandi I, Nabhan SK, Werneck LC, Bittencourt MA et al. Fatal Bacillus cereus meningitis without inflammatory reaction in cerebral spinal fluid after bone marrow transplantation. Transplantation 2003; 76: 1533–1534.

    Article  Google Scholar 

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

    Article  Google Scholar 

  10. Abraham J, Bilgrami S, Dorsky D, Edwards RL, Feingold J, Hill DR et al. Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma following autologous stem cell transplantation. Bone Marrow Transplant 1997; 19: 639–641.

    Article  CAS  Google Scholar 

  11. Frasca KL, Schuster MG . Vancomycin-resistant enterococcal meningitis in an autologous stem cell transplant recipient cured with linezolid. Transpl Infect Dis 2013; 15: E1–E4.

    Article  CAS  Google Scholar 

  12. Fujiwara S, Muroi K, Kikuchi S, Kawano-Yamamoto C, Matsuyama T, Mori M et al. Development of streptococcus meningitis and Epstein-Barr virus reactivation after non-T-cell-depleted human leukocyte antigen-haploidentical peripheral blood stem cell transplantation based on feto-maternal microchimerism. Leuk Lymphoma 2007; 48: 640–642.

    Article  CAS  Google Scholar 

  13. Haase R, Sauer H, Dagwadordsch U, Foell J, Lieser U . Successful treatment of Bacillus cereus meningitis following allogenic stem cell transplantation. Pediatr Transplant 2005; 9: 338–341.

    Article  Google Scholar 

  14. Haddad PA, Repka TL, Weisdorf DJ . Penicillin-resistant Streptococcus pneumoniae septic shock and meningitis complicating chronic graft versus host disease: a case report and review of the literature. Am J Med 2002; 113: 152–155.

    Article  Google Scholar 

  15. Johnson H, MB E, Sharp SE . A 53-year-old stem cell transplant recipient with meningitis and bacteremia. J Clin Microbiol 2011; 49: 4031 421.

    Article  Google Scholar 

  16. 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 

  17. Radice C, Munoz V, Castellares C, Casanova M, Serrano D, Carrion R et al. Listeria monocytogenes meningitis in two allogeneic hematopoietic stem cell transplant recipients. Leuk Lymphoma 2006; 47: 1701–1703.

    Article  CAS  Google Scholar 

  18. Wiesmayr S, Tabarelli W, Stelzmueller I, Nachbaur D, Boesmueller C, Wykypiel H et al. Listeria meningitis in transplant recipients. Wien Klin Wochenschr 2005; 117: 229–233.

    Article  Google Scholar 

  19. D'Antonio D, Di Bartolomeo P, Iacone A, Olioso P, Di Girolamo G, Angrilli F et al. Meningitis due to penicillin-resistant Streptococcus pneumoniae in patients with chronic graft-versus-host disease. Bone Marrow Transplant 1992; 9: 299–300.

    CAS  PubMed  Google Scholar 

  20. Chang J, Powles R, Mehta J, Paton N, Treleaven J, Jameson B . Listeriosis in bone marrow transplant recipients: incidence, clinical features, and treatment. Clin Infect Dis 1995; 21: 1289–1290.

    Article  CAS  Google Scholar 

  21. Tsukada Y, Nagayama H, Mori T, Shimizu T, Sato N, Takayama N et al. Granulocyte transfusion as a treatment for enterococcal meningoencephalitis after allogeneic bone marrow transplantation from an unrelated donor. Bone Marrow Transplant 2003; 31: 69–72.

    Article  CAS  Google Scholar 

  22. Higa T, Tasaka T, Kubo Y, Nakagiri I, Sano F, Matsuhashi Y et al. Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intravenous linezolid in an allogeneic cord blood stem cell transplant recipient. Scand J Infect Dis 2008; 40: 990–992.

    Article  Google Scholar 

  23. Barocci S, Mancini A, Canovari B, Petrelli E, Sbriscia-Fioretti E, Licci A et al. Listeria monocytogenes meningitis in an immunocompromised patient. New Microbiol 2015; 38: 113–118.

    PubMed  Google Scholar 

  24. Zomas A, Mehta J, Powles R, Treleaven J, Iveson T, Singhal S et al. Unusual infections following allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplant 1994; 14: 799–803.

    CAS  PubMed  Google Scholar 

  25. Long SG, Leyland MJ, Milligan DW . Listeria meningitis after bone marrow transplantation. Bone Marrow Transplant 1993; 12: 537–539.

    CAS  PubMed  Google Scholar 

  26. Europdonor Foundation. Europdonor Foundation Annual Report 2012. Leiden 2013. [ONLINE]. Available at file:///H:/Downloads/Annual%20Report%202012%20(1).pdf. (accessed 09 October 2014).

  27. Bijlsma MW, Brouwer MC, Kasanmoentalib ES, Kloek AT, Lucas MJ, Tanck MW et al. Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect Dis 2015; 16: 339–347.

    Article  Google Scholar 

  28. Spanos A, Harrell FE Jr, Durack DT . Differential diagnosis of acute meningitis. An analysis of the predictive value of initial observations. JAMA 1989; 262: 2700–2707.

    Article  CAS  Google Scholar 

  29. Statistics Netherlands. statline.cbs.nl. [ONLINE] Available at http://statline.cbs.nl/Statweb/publication/?DM=SLNL&PA=37296NED&D1=8-13&D2=a&HDR=G1&STB=T&VW=T (accessed 09 June 2015).

  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  Google Scholar 

  31. Fan WC, Liu CJ, Hong YC, Feng JY, Su WJ, Chien SH et al. Long-term risk of tuberculosis in haematopoietic stem cell transplant recipients: a 10-year nationwide study. Int J Tuberc Lung Dis 2015; 19: 58–64.

    Article  Google Scholar 

  32. Robin M, Guardiola P, Devergie A, Yeshurun M, Shapiro S, Esperou H et al. A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors. Leukemia 2005; 19: 1613–1620.

    Article  CAS  Google Scholar 

  33. Koopmans MM, Brouwer MC, Bijlsma MW, Bovenkerk S, Keijzers W, van der Ende A et al. Listeria monocytogenes sequence type 6 and increased rate of unfavorable outcome in meningitis: epidemiologic cohort study. Clin Infect Dis 2013; 57: 247–253.

    Article  Google Scholar 

  34. Tauber MG, Kennedy SL, Tureen JH, Lowenstein DH . Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein. Am J Pathol 1992; 141: 53–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Youssef S, Rodriguez G, Rolston KV, Champlin RE, Raad II, 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 

  36. Guinan EC, Molrine DC, Antin JH, Lee MC, Weinstein HJ, Sallan SE et al. Polysaccharide conjugate vaccine responses in bone marrow transplant patients. Transplantation 1994; 57: 677–684.

    Article  CAS  Google Scholar 

  37. Kumar D, Chen MH, Welsh B, Siegal D, Cobos I, Messner HA et al. A randomized, double-blind trial of pneumococcal vaccination in adult allogeneic stem cell transplant donors and recipients. Clin Infect Dis 2007; 45: 1576–1582.

    Article  Google Scholar 

  38. Cordonnier C, Labopin M, Chesnel V, Ribaud P, De La Camara R, Martino R et al. Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation. Clin Infect Dis 2009; 48: 1392–1401.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  40. Antin JH, Guinan EC, Avigan D, Soiffer RJ, Joyce RM, Martin VJ et al. Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 213–222.

    Article  CAS  Google Scholar 

  41. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Preface. Bone Marrow Transplant 2009; 44: 453–455.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Ronnie van der Holt, PhD and Jeannine Refos, EBMT coordinator, Erasmus MC HOVON data center provided the data about the prevalence of HSCT in The Netherlands. Netherlands Organization for Health Research and Development (ZonMw; NWO-Vedi grant 2010.[016.116.358] to DB NWO-Veni grant 2012.[916.76.023] to MB), the Academic Medical Center (AMC Fellowship 2008 to DB), and the European Research Council (ERC Starting Grant 281156 to DB). The Netherlands Reference laboratory for bacterial Meningitis is supported by the National Institute of Public health and the Environmental Protection, Bilthoven.

Author information

Authors and Affiliations

  1. Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    K E B van Veen, M C Brouwer & D van de Beek

  2. Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands

    K E B van Veen

  3. Department of Medical Microbiology and The Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    A van der Ende

Authors
  1. K E B van Veen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M C Brouwer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A van der Ende
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D van de Beek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D van de Beek.

Ethics declarations

Competing interests

The authors declare 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

van Veen, K., Brouwer, M., van der Ende, A. et al. Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study. Bone Marrow Transplant 51, 1490–1495 (2016). https://doi.org/10.1038/bmt.2016.181

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.181

This article is cited by

Search

Advanced search

Quick links