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Impact of neutropenia on the clinical outcomes of Staphylococcus aureus bacteremia in patients with hematologic malignancies: a 10-year experience in a tertiary care hospital

  • Byung-Han Ryu
  • Seung Cheol Lee
  • Minjeong Kim
  • Yewon Eom
  • Jiwon Jung
  • Min Jae Kim
  • Heungsup Sung
  • Mi-Na Kim
  • Sung-Han Kim
  • Sang-Oh Lee
  • Sang-Ho Choi
  • Jun Hee Woo
  • Yang Soo KimEmail author
  • Yong Pil ChongEmail author
Original Article
  • 29 Downloads

Abstract

Staphylococcus aureus bacteremia is one of the most serious bacterial infections and may lead to worse clinical outcomes in patients with prolonged severe neutropenia. However, clinical data on S. aureus bacteremia in neutropenic patients with hematologic malignancies are limited. We conducted two case-control studies using a 10-year prospective cohort of patients with S. aureus bacteremia. Neutropenic and non-neutropenic hematologic malignancy patients were compared on clinical characteristics and treatment outcomes. An additional matched case-control study using solid tumor patients was conducted. Risk factors for 12-week mortality were analyzed. Of 1643 patients with S. aureus bacteremia, 64 (3.9%) neutropenic and 108 (6.6%) non-neutropenic patients with hematologic malignancies were included in the study. There were no significant differences in the incidence of metastatic infection between the two groups (17.2% vs. 17.6%, p = 0.95), in contrast with a previous study that observed no metastatic infection in neutropenic patients. Twelve-week mortality in neutropenic patients with hematologic malignancies tended to be lower than in non-neutropenic patients with hematologic malignancies (15.6% vs. 26.9%, p = 0.09) and was significantly lower than in neutropenic patients with solid tumors (15.6% vs. 45.8%, p = 0.003). Independent risk factors for mortality in hematologic malignancy patients with S. aureus bacteremia were high Charlson comorbidity score, high APACHE II score, and skin and soft tissue infection. Neutropenia was not independently associated with mortality. Our findings suggest that neutropenia in hematologic malignancies may not affect the incidence of metastatic infection or 12-week mortality of S. aureus bacteremia.

Keywords

Staphylococcus aureus Bacteremia Neutropenia Hematologic malignancies 

Notes

Funding information

This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI15C2918).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval and consent to participate

This study was approved by the Asan Medical Center Institutional Review Board.

Supplementary material

10096_2019_3802_MOESM1_ESM.doc (80 kb)
ESM 1 (DOC 79.5 kb)

References

  1. 1.
    Safdar A, Armstrong D (2011) Infections in patients with hematologic neoplasms and hematopoietic stem cell transplantation: neutropenia, humoral, and splenic defects. Clin Infect Dis 53(8):798–806.  https://doi.org/10.1093/cid/cir492 CrossRefPubMedGoogle Scholar
  2. 2.
    Ramphal R (2004) Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens. Clin Infect Dis 39(Suppl 1):S25–S31.  https://doi.org/10.1086/383048 CrossRefPubMedGoogle Scholar
  3. 3.
    Rosenberg PS, Alter BP, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Fier C, Freedman M, Kannourakis G, Kinsey S, Schwinzer B, Zeidler C, Welte K, Dale DC (2006) The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 107(12):4628–4635.  https://doi.org/10.1182/blood-2005-11-4370 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Gudiol C, Tubau F, Calatayud L, Garcia-Vidal C, Cisnal M, Sanchez-Ortega I, Duarte R, Calvo M, Carratala J (2011) Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes. J Antimicrob Chemother 66(3):657–663.  https://doi.org/10.1093/jac/dkq494 CrossRefPubMedGoogle Scholar
  5. 5.
    Cattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, Signorini L, Re A, Carosi G, Rossi G (2008) Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution. J Antimicrob Chemother 61(3):721–728.  https://doi.org/10.1093/jac/dkm514 CrossRefPubMedGoogle Scholar
  6. 6.
    Bousquet A, Malfuson JV, Sanmartin N, Konopacki J, MacNab C, Souleau B, de Revel T, Elouennass M, Samson T, Soler C, Foissaud V, Martinaud C (2014) An 8-year survey of strains identified in blood cultures in a clinical haematology unit. Clin Microbiol Infect 20(1):O7–O12.  https://doi.org/10.1111/1469-0691.12294 CrossRefGoogle Scholar
  7. 7.
    Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr (2015) Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 28(3):603–661.  https://doi.org/10.1128/cmr.00134-14 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Espersen F, Frimodt-Moller N, Rosdahl VT, Jessen O, Faber V, Rosendal K (1987) Staphylococcus aureus bacteremia in patients with hematological malignancies and/or agranulocytosis. Acta Med Scand 222(5):465–470CrossRefGoogle Scholar
  9. 9.
    Skov R, Gottschau A, Skinhoj P, Frimodt-Moller N, Rosdahl VT, Espersen F (1995) Staphylococcus aureus bacteremia: a 14-year nationwide study in hematological patients with malignant disease or agranulocytosis. Scand J Infect Dis 27(6):563–568CrossRefGoogle Scholar
  10. 10.
    Shah MA, Sanders L, Lanclos K, Chamis AL, Gockerman J, Wray D, Corey GR, Fowler VG Jr (2002) Staphylococcus aureus bacteremia in patients with neutropenia. South Med J 95(7):782–784CrossRefGoogle Scholar
  11. 11.
    Venditti M, Falcone M, Micozzi A, Carfagna P, Taglietti F, Serra PF, Martino P (2003) Staphylococcus aureus bacteremia in patients with hematologic malignancies: a retrospective case-control study. Haematologica 88(8):923–930PubMedGoogle Scholar
  12. 12.
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52(4):427–431.  https://doi.org/10.1093/cid/ciq147 CrossRefPubMedGoogle Scholar
  13. 13.
    Mc CW, Jackson G (1962) Gram-negative bacteremia: I. etiology and ecology. Arch Intern Med 110(6):847–855.  https://doi.org/10.1001/archinte.1962.03620240029006 CrossRefGoogle Scholar
  14. 14.
    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):373–383CrossRefGoogle Scholar
  15. 15.
    Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM (1988) CDC definitions for nosocomial infections, 1988. Am J Infect Control 16(3):128–140CrossRefGoogle Scholar
  16. 16.
    Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49(1):1–45.  https://doi.org/10.1086/599376 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR (2000) Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 30(4):633–638.  https://doi.org/10.1086/313753 CrossRefPubMedGoogle Scholar
  18. 18.
    Jenkins TC, Price CS, Sabel AL, Mehler PS, Burman WJ (2008) Impact of routine infectious diseases service consultation on the evaluation, management, and outcomes of Staphylococcus aureus bacteremia. Clin Infect Dis 46(7):1000–1008.  https://doi.org/10.1086/529190 CrossRefPubMedGoogle Scholar
  19. 19.
    Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Reller LB, Sexton DJ (2002) Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137(10):791–797CrossRefGoogle Scholar
  20. 20.
    Gonzalez-Barca E, Carratala J, Mykietiuk A, Fernandez-Sevilla A, Gudiol F (2001) Predisposing factors and outcome of Staphylococcus aureus bacteremia in neutropenic patients with cancer. Eur J Clin Microbiol Infect Dis 20(2):117–119CrossRefGoogle Scholar
  21. 21.
    van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB (2012) Predictors of mortality in Staphylococcus aureus bacteremia. Clin Microbiol Rev 25(2):362–386.  https://doi.org/10.1128/cmr.05022-11 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Fowler VG Jr, Olsen MK, Corey GR, Woods CW, Cabell CH, Reller LB, Cheng AC, Dudley T, Oddone EZ (2003) Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 163(17):2066–2072.  https://doi.org/10.1001/archinte.163.17.2066 CrossRefPubMedGoogle Scholar
  23. 23.
    Sotman SB, Schimpff SC, Young VM (1980) Staphylococcus aureus bacteremia in patients with acute leukemia. Am J Med 69(6):814–818CrossRefGoogle Scholar
  24. 24.
    Thwaites GE, Gant V (2011) Are bloodstream leukocytes Trojan horses for the metastasis of Staphylococcus aureus? Nat Rev Microbiol 9(3):215–222.  https://doi.org/10.1038/nrmicro2508 CrossRefPubMedGoogle Scholar
  25. 25.
    Tanaka F, Goto H, Yokosuka T, Yanagimachi M, Kajiwara R, Naruto T, Nishimaki S, Yokota S (2009) Suppressed neutrophil function in children with acute lymphoblastic leukemia. Int J Hematol 90(3):311–317.  https://doi.org/10.1007/s12185-009-0412-4 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Infectious DiseasesGyeongsang National University Changwon HospitalChangwonRepublic of Korea
  2. 2.Department of Infectious Diseases and Department of Medical science, Asan Medical Institute of Convergence Science and Technology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  3. 3.Department of Infectious Diseases, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  4. 4.Department of Laboratory Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

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