Current Infectious Disease Reports

, Volume 12, Issue 5, pp 392–400 | Cite as

Staphylococcal Toxic Shock Syndrome: Mechanisms and Management

  • Jonathan A. Silversides
  • Emma Lappin
  • Andrew J. Ferguson


Staphylococcal toxic shock syndrome is a rare complication of Staphylococcus aureus infection in which bacterial toxins act as superantigens, activating very large numbers of T cells and generating an overwhelming immune-mediated cytokine avalanche that manifests clinically as fever, rash, shock, and rapidly progressive multiple organ failure, often in young, previously healthy patients. The syndrome can occur with any site of S. aureus infection, and so clinicians of all medical specialties should have a firm grasp of the presentation and management. In this article, we review the literature on the pathophysiology, clinical features, and treatment of this serious condition with emphasis on recent insights into pathophysiology and on information of relevance to the practicing clinician.


Staphylococcus aureus Superantigen Toxic shock syndrome Septic shock Infection Gram-positive Immunoglobulin Clindamycin Linezolid Daptomycin Tigecycline Toll-like receptor T-cell receptor Cytokine Systemic inflammatory response syndrome Early goal-directed therapy Nuclear factor-κB Tumor necrosis factor-α Interleukin-10 Immunomodulation Toxic shock syndrome toxin-1 Methicillin-resistant Staphylococcus aureus (MRSA) Pathogen-associated molecular patterns (PAMP) Polymorphism 



No potential conflict of interest relevant to this article was reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Todd J, Fishaut M, Kapral F, et al.: Toxic-shock syndrome associated with phage-group-1 staphylococci. Lancet 1978, 2:1116–1118.CrossRefPubMedGoogle Scholar
  2. 2.
    Hajjeh RA, Reingold A, Weil A, et al.: Toxic shock syndrome in the United States: surveillance update, 1979–1996. Emerg Infect Dis 1999, 5:807–810.CrossRefPubMedGoogle Scholar
  3. 3.
    Centers for Disease Control and Prevention (CDC): Notifiable diseases and mortality tables. MMWR 2010, 59:398–411.Google Scholar
  4. 4.
    Schlievert PM, Tripp TJ, Peterson ML: Reemergence of staphylococcal toxic shock syndrome in Minneapolis-St Paul, Minnesota, during the 2000–2003 surveillance period. J Clin Microbiol 2004, 42:2875–2876.CrossRefPubMedGoogle Scholar
  5. 5.
    Wertheim HFL, Melles DC, Vos MC, et al.: The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 2005, 5:751–762.CrossRefPubMedGoogle Scholar
  6. 6.
    Guinan ME, Dan BB, Guidotti RJ, et al.: Vaginal colonization with Staphylococcus aureus in healthy women. Ann Intern Med 1982, 96:944–947.PubMedGoogle Scholar
  7. 7.
    Schlebusch S, Schooneveldt JM, Huygens F, et al.: Prevalence of Staphylococcus aureus strains in an Australian cohort, 1989–2003: evidence for the low prevalence of the toxic shock toxin and Panton–Valentine leukocidin genes. Eur J Clin Microbiol Infect Dis 2009, 28:1183–1189.CrossRefPubMedGoogle Scholar
  8. 8.
    Parsonnet J, Hansmann MA, Delaney ML, et al.: Prevalence of toxic shock syndrome toxin 1-producing Staphylococcus aureus and the presence of antibodies to this superantigen in menstruating women. J Clin Microbiol 2005, 43:4628–4634.CrossRefPubMedGoogle Scholar
  9. 9.
    Durand G, Bes, M, Meugnier H, et al.: Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France. J Clin Microbiol 2006, 44:847–853.CrossRefPubMedGoogle Scholar
  10. 10.
    Parsonnet J, Goering RV, Hansmann MA, et al.: Prevalence of toxic shock syndrome toxin 1 (TSST-1)-producing strains of Staphylococcus aureus and antibody to TSST-1 among healthy Japanese women. J Clin Microbiol 2008, 46:2731–2738.CrossRefPubMedGoogle Scholar
  11. 11.
    Souza RR, Coelho LR, Botelho AMN, et al.: Biofilm formation and prevalence of lukF-pv, seb, sec and tst genes among hospital- and community-acquired isolates of some international methicillin-resistant Staphylococcus aureus lineages. Clin Microbiol Infect 2009, 15:203–207.CrossRefPubMedGoogle Scholar
  12. 12.
    Limbago B, Fosheim GE, Schoonover V, et al.: Characterization of methicillin-resistant Staphylococcus aureus isolates collected in 2005 and 2006 from patients with invasive disease: a population-based analysis. J Clin Microbiol 2009, 47:1344–1351.CrossRefPubMedGoogle Scholar
  13. 13.
    Hu D, Omoe K, Inoue F, et al.: Comparative prevalence of superantigenic toxin genes in meticillin-resistant and methicillin susceptible Staphylococcus aureus isolates. J Med Microbiol 2008, 57:1106–1112.CrossRefPubMedGoogle Scholar
  14. 14.
    •• Fraser JD, Proft T: The bacterial superantigen and superantigen-like proteins. Immunol Rev 2008, 225:226–243. A thorough and useful overview of the current knowledge of superantigen structure, activity, and the pathophysiology of superantigen-mediated disease.CrossRefPubMedGoogle Scholar
  15. 15.
    White J, Herman A, Pullen AM, et al.: The V-beta specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 1989, 56:27–35.CrossRefPubMedGoogle Scholar
  16. 16.
    Llewelyn M, Cohen J: Superantigens: microbial agents that corrupt immunity. Lancet Infect Dis 2002, 2:156–162.CrossRefPubMedGoogle Scholar
  17. 17.
    • Thomas D, Dauwalder O, Brun V, et al.: Staphylococcus aureus superantigens elicit redundant and extensive human Vβ patterns. Infect Immun 2009, 77:2043–2050. This study goes into considerable depth to elucidate specific superantigen Vβ signatures, although the authors found significant variation and overlap in Vβ T-cell responses to staphylococcal superantigens.CrossRefPubMedGoogle Scholar
  18. 18.
    McCormick JK, Yarwood JM, Schlievert PM: Toxic shock syndrome and bacterial superantigens: an update. Annu Rev Microbiol 2001, 55:77–104.CrossRefPubMedGoogle Scholar
  19. 19.
    Faulkner L, Cooper A, Fantino C, et al.: The mechanism of superantigen mediated toxic shock: not a simple Th1 cytokine storm. J Immunol 2005, 175: 6870–6877.PubMedGoogle Scholar
  20. 20.
    Trede NS, Castigli E, Geha RS, et al.: Microbial superantigens induce NF-kappa B in the human monocytic cell line THP-1. J Immunol 1993, 150:5604–5613.PubMedGoogle Scholar
  21. 21.
    Hopkins P, Pridmore AC, Ellmerich S, et al.: Increased surface toll-like receptor 2 expression in superantigen shock. Crit Care Medicine 2008, 36:1267–1276.CrossRefGoogle Scholar
  22. 22.
    • Iwasaki A, Medzhitov R: Regulation of adaptive immunity by the innate immune system. Science 2010, 327: 291–295. This article provides a very good review of the process of pathogen recognition by the host, including secreted, transmembrane, and cytosolic receptors for pathogen-associated molecular patterns.CrossRefPubMedGoogle Scholar
  23. 23.
    • Chau TA, McCully ML, Brintnell W, et al.: Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome. Nat Med 2009, 15:641–649. This study offers a potential explanation for the low frequency of toxic shock syndrome despite widespread colonization and infection, based on the ability of TLR2 activation to modulate inflammation.CrossRefPubMedGoogle Scholar
  24. 24.
    •• Mele T, Madrenas J: TLR2 signalling: at the crossroads of commensalism, invasive infections and toxic shock syndrome by Staphylococcus aureus. Int J Biochem Cell Biol 2010 (Epub ahead of print). An excellent review highlighting the potential for TLR2-mediated immunomodulation and the impact of a dual pro- and anti-inflammatory outcome from staphylococcal exposure on our approach to TSS.Google Scholar
  25. 25.
    Brosnahan A, Mantz MJ, Squier CA, et al.: Cytolysins augment the superantigen penetration of stratified mucosa. J Immunol 2009, 182:2364–2373.CrossRefPubMedGoogle Scholar
  26. 26.
    Stolz SJ, Davis JP, Vergeront JM, et al.: Development of serum antibody to toxic shock toxin among individuals with toxic shock syndrome in Wisconsin. J Infect Dis 1985, 151:883–889.PubMedGoogle Scholar
  27. 27.
    Llewelyn M, Sriskandan S, Peakman M, et al.: HLA class II polymorphisms determine responses to bacterial superantigens. J Immunol 2004, 172:1719–1726.PubMedGoogle Scholar
  28. 28.
    Strausburgh LJ: Toxic shock syndrome: are you recognizing its changing presentations? Postgrad Med 1993, 94:107–108.Google Scholar
  29. 29.
    El-Fiky LM, Khamis N, Mostafa Bel D, Adly AM: Staphylococcal infection and toxin production in chronic rhinosinusitis. Am J Rhinol Allergy 2009, 23:264–267.CrossRefPubMedGoogle Scholar
  30. 30.
    Chan KH, Kraai TL, Richter GT, et al.: Toxic shock syndrome and rhinosinusitis in children. Arch Otolaryngol Head Neck Surg 2009, 135:538–542.CrossRefPubMedGoogle Scholar
  31. 31.
    Wharton M, Chorba Tl, Vogt RL, et al.: Case definitions for public health surveillance. MMWR Recomm Rep 1990, 39:1–43.PubMedGoogle Scholar
  32. 32.
    Waclavicek M, Stich N, Rappan I, et al.: Analysis of the early response to TSST-1 reveals Vbeta-unrestricted extravasation, compartmentalization of the response, and unresponsiveness but not anergy to TSST-1. J Leukoc Biol 2009, 85:44–54.CrossRefPubMedGoogle Scholar
  33. 33.
    Granger K, Rundell MS, Pingle MR, et al.: Multiplex PCR-ligation detection reaction assay for simultaneous detection of drug resistance and toxin genes from Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium. J Clin Microbiol 2010, 48:277–280.CrossRefPubMedGoogle Scholar
  34. 34.
    Javid Khojasteh V, Rogan MT, Edwards-Jones V, et al.: Detection of antibodies to Staphylococcus aureus toxic shock syndrome toxin-1 using a competitive agglutination inhibition assay. Lett Appl Microbiol 2003, 36:372–376.CrossRefPubMedGoogle Scholar
  35. 35.
    Ferry T, Thomas D, Perpoint T, et al.: Analysis of superantigenic toxin Vb T-cell signatures produced during cases of staphylococcal toxic shock syndrome and septic shock. Clin Microbiol Infect 2008, 14: 546–554.CrossRefPubMedGoogle Scholar
  36. 36.
    Ferry T, Thomas D, Bouchut J, et al.: Early diagnosis of staphylococcal toxic shock syndrome by detection of the tsst-1 v beta signature in peripheral blood of a 12-year-old boy. Ped Infect Dis J 2008, 27:274–277.CrossRefGoogle Scholar
  37. 37.
    • Gbaguidi-Haore H,Thouverez M, Couetdic G, et al.: Usefulness of antimicrobial resistance pattern for detecting PVL- or TSST-1-producing methicillin resistant Staphylococcus aureus in a French university hospital. J Med Microbiol 2009, 58:1337–1342. This useful paper demonstrates the potential to determine the likelihood of toxin production by MRSA based on local antimicrobial resistance pattern, once a reference study on toxin production by local isolates has been done.CrossRefPubMedGoogle Scholar
  38. 38.
    •• Dellinger RP, Levy MM, Carlet JM, et al.: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Int Care Med 2008, 34:17–60. This article provides an evidence-based, worldwide, consensus statement on current therapy for sepsis and septic shock, emphasizing the importance of early intervention and attention to detail.CrossRefGoogle Scholar
  39. 39.
    Rivers E, Nguyen B, Havstad S, et al.: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368–1377.CrossRefPubMedGoogle Scholar
  40. 40.
    • Jones AE, Shapiro NI, Trzeciak S, et al.: Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010, 303:739–746. This article describes a randomized controlled trial of two resuscitation endpoints, demonstrating noninferiority of the more readily measured lactate clearance as compared to central venous oxygen saturation.CrossRefPubMedGoogle Scholar
  41. 41.
    DeBacker D, Biston P, Devriendt J, et al.: Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010, 362:779–789.CrossRefGoogle Scholar
  42. 42.
    Gupta V, Datta P, Rani H, Chander J: Inducible clindamycin resistance in Staphylococcus aureus: a study from North India. J Postgrad Med 2009, 55:176–179.CrossRefPubMedGoogle Scholar
  43. 43.
    Zhanel GG, DeCorby M, Nichol KA, et al.: Characterization of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Escherichia coli in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) study (2005–2006). Can J Infect Dis Med Microbiol 2008, 19:243–249.PubMedGoogle Scholar
  44. 44.
    Stevens DL, Ma Y, Salmi DB, et al.: Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis 2007, 195:202–211.CrossRefPubMedGoogle Scholar
  45. 45.
    Saliba R, Paasch L, El Solh A: Tigecycline attenuates staphylococcal superantigen-induced T-cell proliferation and production of cytokines and chemokines. Immunopharmacol Immunotoxicol 2009, 31:583–588.CrossRefPubMedGoogle Scholar
  46. 46.
    Baudoux P, Lemaire S, Denis O, et al.: Activity of quinupristin/dalfopristin against extracellular and intracellular Staphylococcus aureus with various resistance phenotypes. J Antimicrob Chemother 2010, 65:1228–1236.CrossRefPubMedGoogle Scholar
  47. 47.
    Schlievert PM: Use of intravenous immunoglobulin in the treatment of staphylococcal and streptococcal toxic shock syndromes and related illnesses. J Allergy Clin Immunol 2001, 108:S107–S110.CrossRefPubMedGoogle Scholar
  48. 48.
    Darenberg J, Ihendyane N, Sjolin J: Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003, 37:333–340.CrossRefPubMedGoogle Scholar
  49. 49.
    Kato K, Sakamoto T, Ito K: Gamma-globulin inhibits superantigen-induced lymphocyte proliferation and cytokine production. Allergol Int 2007, 56: 439–444.CrossRefPubMedGoogle Scholar
  50. 50.
    Darenberg J, Söderquist B, Normark BH, Norrby-Teglund A: Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. Clin Infect Dis 2004, 38:836–842.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jonathan A. Silversides
    • 1
  • Emma Lappin
    • 2
  • Andrew J. Ferguson
    • 3
  1. 1.Specialty Registrar in Anaesthesia and Intensive Care Medicine, Regional Intensive Care UnitRoyal Victoria HospitalBelfastUK
  2. 2.Specialist Registrar in AnaesthesiaBelfast City HospitalBelfastUK
  3. 3.Consultant in Intensive Care Medicine and AnaesthesiaCraigavon Area HospitalPortadownUK

Personalised recommendations