Staphylococcus aureus bacteremia in immunosuppressed patients: a multicenter, retrospective cohort study

  • G. Sasson
  • A. D. Bai
  • A. Showler
  • L. Burry
  • M. Steinberg
  • D. R. Ricciuto
  • T. Fernandes
  • A. Chiu
  • S. Raybardhan
  • M. Science
  • E. Fernando
  • A. M. Morris
  • C. M. Bell
Original Article
  • 188 Downloads

Abstract

Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88–1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78–1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p < 0.0001, IC: p < 0.0001) and early embolic stroke (IS: p < 0.0001, IC: p = 0.0272). Congestive heart failure was a mortality predictor in the IS cohort (p = 0.0089). Fever within 24 h (p = 0.0092) and early skin and soft tissue infections (p < 0.0001) were survival predictors in the IS cohort. SAB causes significant mortality regardless of pre-existing immune status, but immunosuppressed patients do not have an elevated risk of mortality relative to immunocompetent patients.

Notes

Acknowledgments

This project was performed in collaboration with the Toronto Antimicrobial Stewardship Corridor (TASC). We are indebted to Pamilla Cheema, Bin Chen, Karol Sitarski, Bruce Tugwood, Bonnie Chi Thieu, Mei Shi, and Rochelle Liem for their assistance with the data collection and verification.

Compliance with ethical standards

Funding

This study was carried out as part of our routine work. The Sinai Health System-University Health Network Antimicrobial Stewardship Program was supported by an unrestricted educational grant from Pfizer Canada from 2010 to 2012, which partially supported the salary of a research coordinator (M. Steinberg). A Sinai Health System Department of Medicine Summer Studentship Award funded A. Bai. A. Morris receives partial salary support for his antimicrobial stewardship activities from Sinai Health System and University Health Network. A CIHR/CPSI Chair in Patient Safety and Continuity of Care supports C. Bell.

Conflict of interest

No authors had any conflicts of interest to declare.

Ethical approval

Research Ethics Board approval was obtained at each of the participating sites.

Informed consent

All Research Ethics Boards approved waiver of consent due to the retrospective nature of the study.

References

  1. 1.
    Chang FY, MacDonald BB, Peacock JE Jr, Musher DM, Triplett P, Mylotte JM, O’Donnell A, Wagener MM, Yu VL (2003) A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore) 82:322–332CrossRefGoogle Scholar
  2. 2.
    Kaech C, Elzi L, Sendi P, Frei R, Laifer G, Bassetti S, Fluckiger U (2006) Course and outcome of Staphylococcus aureus bacteraemia: a retrospective analysis of 308 episodes in a Swiss tertiary-care centre. Clin Microbiol Infect 12:345–352CrossRefPubMedGoogle Scholar
  3. 3.
    Incani A, Hair C, Purnell P, O’Brien DP, Cheng AC, Appelbe A, Athan E (2013) Staphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis. Eur J Clin Microbiol Infect Dis 32(8):1003–1008CrossRefPubMedGoogle Scholar
  4. 4.
    Fowler VG Jr, Li J, Corey GR, Boley J, Marr KA, Gopal AK, Kong LK, Gottlieb G, Donovan CL, Sexton DJ, Ryan T (1997) Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol 30:1072–1078CrossRefPubMedGoogle Scholar
  5. 5.
    Wang FD, Chen YY, Chen TL, Liu CY (2008) Risk factors and mortality in patients with nosocomial Staphylococcus aureus bacteremia. Am J Infect Control 36(2):118–122CrossRefPubMedGoogle Scholar
  6. 6.
    Lefort A, Panhard X, Clermont O, Woerther PL, Branger C, Mentré F, Fantin B, Wolff M, Denamur E; COLIBAFI Group (2011) Host factors and portal of entry outweigh bacterial determinants to predict the severity of Escherichia coli bacteremia. J Clin Microbiol 49(3):777–783CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Greenberg JA, David MZ, Hall JB, Kress JP (2014) Immune dysfunction prior to Staphylococcus aureus bacteremia is a determinant of long-term mortality. PLoS One 9(2):e88197CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Poutsiaka DD, Davidson LE, Kahn KL, Bates DW, Snydman DR, Hibberd PL (2009) Risk factors for death after sepsis in patients immunosuppressed before the onset of sepsis. Scand J Infect Dis 41:469–479CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mrus JM, Braun L, Yi MS, Linde-Zwirble WT, Johnston JA (2005) Impact of HIV/AIDS on care and outcomes of severe sepsis. Crit Care 9(6):R623–R630CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Silva JM Jr, dos Santos Sde S (2013) Sepsis in AIDS patients: clinical, etiological and inflammatory characteristics. J Int AIDS Soc 16(1):17344CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hill EE, Vanderschueren S, Verhaegen J, Herijgers P, Claus P, Herregods MC, Peetermans WE (2007) Risk factors for infective endocarditis and outcome of patients with Staphylococcus aureus bacteremia. Mayo Clin Proc 82(10):1165–1169CrossRefPubMedGoogle Scholar
  12. 12.
    Bai AD, Showler A, Burry L, Steinberg M, Ricciuto DR, Fernandes T, Chiu A, Raybardhan S, Science M, Fernando E, Tomlinson G, Bell CM, Morris AM (2015) Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study. J Antimicrob Chemother 70(5):1539–1546CrossRefPubMedGoogle Scholar
  13. 13.
    Bai AD, Showler A, Burry L, Steinberg M, Ricciuto DR, Fernandes T, Chiu A, Raybardhan S, Science M, Fernando E, Tomlinson G, Bell CM, Morris AM (2015) Impact of Infectious disease consultation on quality of care, mortality, and length of stay in Staphylococcus aureus bacteremia: results from a large multicenter cohort study. Clin Infect Dis 60(10):1451–1461CrossRefPubMedGoogle Scholar
  14. 14.
    Bai AD, Burry L, Showler A, Steinberg M, Ricciuto D, Fernandes T, Chiu A, Raybardhan S, Tomlinson GA, Bell CM, Morris AM (2015) Usefulness of previous methicillin-resistant Staphylococcus aureus screening results in guiding empirical therapy for S aureus bacteremia. Can J Infect Dis Med Microbiol 26(4):201–206PubMedPubMedCentralGoogle Scholar
  15. 15.
    Showler A, Burry L, Bai AD, Steinberg M, Ricciuto DR, Fernandes T, Chiu A, Raybardhan S, Science M, Fernando E, Bell CM, Morris AM (2015) Use of transthoracic echocardiography in the management of low-risk Staphylococcus aureus bacteremia: results from a retrospective multicenter cohort study. JACC Cardiovasc Imaging 8(8):924–931CrossRefPubMedGoogle Scholar
  16. 16.
    Thampi N, Showler A, Burry L, Bai AD, Steinberg M, Ricciuto DR, Bell CM, Morris AM (2015) Multicenter study of health care cost of patients admitted to hospital with Staphylococcus aureus bacteremia: impact of length of stay and intensity of care. Am J Infect Control 43(7):739–744CrossRefPubMedGoogle Scholar
  17. 17.
    Clinical and Laboratory Standards Institute (CLSI) (2013) Performance standards for antimicrobial susceptibility testing; Twenty-third informational supplement. CLSI document M100-S23. CLSI, Wayne, PAGoogle Scholar
  18. 18.
    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):791–797CrossRefPubMedGoogle Scholar
  19. 19.
    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):633–638CrossRefPubMedGoogle Scholar
  20. 20.
    Mermel LA, Farr BM, Sherertz RJ, Raad II, O’Grady N, Harris JS, Craven DE; Infectious Diseases Society of America; American College of Critical Care Medicine; Society for Healthcare Epidemiology of America (2001) Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32(9):1249–1272CrossRefPubMedGoogle Scholar
  21. 21.
    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):1–45CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Honda H, Krauss MJ, Jones JC, Olsen MA, Warren DK (2010) The value of infectious diseases consultation in Staphylococcus aureus bacteremia. Am J Med 123(7):631–637CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group (2007) Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 116(15):1736–1754CrossRefPubMedGoogle Scholar
  24. 24.
    Fowler VG Jr, Sanders LL, Sexton DJ, Kong L, Marr KA, Gopal AK, Gottlieb G, McClelland RS, Corey GR (1998) Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients. Clin Infect Dis 27(3):478–486CrossRefPubMedGoogle Scholar
  25. 25.
    Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRefGoogle Scholar
  26. 26.
    Laupland KB, Ross T, Gregson DB (2008) Staphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000–2006. J Infect Dis 198(3):336–343CrossRefPubMedGoogle Scholar
  27. 27.
    Manzur A, Vidal M, Pujol M, Cisnal M, Hornero A, Masuet C, Peña C, Gudiol F, Ariza J (2007) Predictive factors of meticillin resistance among patients with Staphylococcus aureus bloodstream infections at hospital admission. J Hosp Infect 66(2):135–141CrossRefPubMedGoogle Scholar
  28. 28.
    Wyllie DH, Crook DW, Peto TE (2006) Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 1997–2003: cohort study. BMJ 333(7562):281CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhøj P, Frimodt-Møller N (2002) Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases. Arch Intern Med 162(1):25–32CrossRefPubMedGoogle Scholar
  30. 30.
    Hill PC, Birch M, Chambers S, Drinkovic D, Ellis-Pegler RB, Everts R, Murdoch D, Pottumarthy S, Roberts SA, Swager C, Taylor SL, Thomas MG, Wong CG, Morris AJ (2001) Prospective study of 424 cases of Staphylococcus aureus bacteraemia: determination of factors affecting incidence and mortality. Intern Med J 31(2):97–103CrossRefPubMedGoogle Scholar
  31. 31.
    Tumbarello M, de Gaetano Donati K, Tacconelli E, Citton R, Spanu T, Leone F, Fadda G, Cauda R (2002) Risk factors and predictors of mortality of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in HIV-infected patients. J Antimicrob Chemother 50(3):375–382CrossRefPubMedGoogle Scholar
  32. 32.
    Thyrault M, Gachot B, Chastang C, Souweine B, Timsit JF, Bédos JP, Régnier B, Wolff M (1997) Septic shock in patients with the acquired immunodeficiency syndrome. Intensive Care Med 23(10):1018–1023CrossRefPubMedGoogle Scholar
  33. 33.
    Japiassú AM, Amâncio RT, Mesquita EC, Medeiros DM, Bernal HB, Nunes EP, Luz PM, Grinsztejn B, Bozza FA (2010) Sepsis is a major determinant of outcome in critically ill HIV/AIDS patients. Crit Care 14(4):R152CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Yehia BR, Fleishman JA, Wilson L, Hicks PL, Gborkorquellie TT, Gebo KA; HIV Research Network (2011) Incidence of and risk factors for bacteraemia in HIV-infected adults in the era of highly active antiretroviral therapy. HIV Med 12(9):535–543CrossRefPubMedGoogle Scholar
  35. 35.
    Huson MA, Stolp SM, van der Poll T, Grobusch MP (2014) Community-acquired bacterial bloodstream infections in HIV-infected patients: a systematic review. Clin Infect Dis 58(1):79–92CrossRefPubMedGoogle Scholar
  36. 36.
    Narasimhan M, Posner AJ, DePalo VA, Mayo PH, Rosen MJ (2004) Intensive care in patients with HIV infection in the era of highly active antiretroviral therapy. Chest 125(5):1800–1804CrossRefPubMedGoogle Scholar
  37. 37.
    Amancio RT, Japiassu AM, Gomes RN, Mesquita EC, Assis EF, Medeiros DM, Grinsztejn B, Bozza PT, Castro-Faria Neto HC, Bozza FA (2013) The innate immune response in HIV/AIDS septic shock patients: a comparative study. PLoS One 8(7):e68730CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Póvoa P, Souza-Dantas VC, Soares M, Salluh JF (2011) C-reactive protein in critically ill cancer patients with sepsis: influence of neutropenia. Crit Care 15(3):R129CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Gruneir A, Dhalla IA, van Walraven C, Fischer HD, Camacho X, Rochon PA, Anderson GM (2011) Unplanned readmissions after hospital discharge among patients identified as being at high risk for readmission using a validated predictive algorithm. Open Med 5(2):e104–e111PubMedPubMedCentralGoogle Scholar
  40. 40.
    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):362–386CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • G. Sasson
    • 1
  • A. D. Bai
    • 2
  • A. Showler
    • 1
    • 3
  • L. Burry
    • 4
    • 5
  • M. Steinberg
    • 4
  • D. R. Ricciuto
    • 3
    • 6
  • T. Fernandes
    • 7
  • A. Chiu
    • 7
  • S. Raybardhan
    • 8
  • M. Science
    • 9
  • E. Fernando
    • 1
  • A. M. Morris
    • 1
    • 3
    • 4
    • 10
  • C. M. Bell
    • 1
    • 4
    • 10
    • 11
  1. 1.Department of MedicineUniversity of TorontoTorontoCanada
  2. 2.Department of MedicineQueen’s UniversityKingstonCanada
  3. 3.Division of Infectious DiseasesUniversity of TorontoTorontoCanada
  4. 4.Sinai Health SystemTorontoCanada
  5. 5.Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada
  6. 6.Lakeridge HealthOshawaCanada
  7. 7.Trillium Health PartnersMississaugaCanada
  8. 8.North York General HospitalTorontoCanada
  9. 9.Hospital for Sick ChildrenTorontoCanada
  10. 10.University Health NetworkTorontoCanada
  11. 11.Institute for Clinical Evaluative SciencesTorontoCanada

Personalised recommendations