, Volume 72, Issue 9, pp 1213–1227 | Cite as

Invasive Group A Streptococcal Disease

Epidemiology, Pathogenesis and Management
  • Andrew C. SteerEmail author
  • Theresa Lamagni
  • Nigel Curtis
  • Jonathan R. Carapetis
Review Article


Invasive group A streptococcal infections are uncommon, although serious, infections with high case fatality rates. Periodic resurgences in invasive group A streptococcal infections in industrialized countries have been reported from the 1980s onwards, with current estimates of incidence in these countries of approximately 3–4 per 100000 population. Infants, pregnant women and the elderly are at increased risk of invasive group A streptococcal infection. The group A streptococcus has an array of virulence factors that underpin its invasive capacity and, in approximately 10% of cases, super-antigen toxins produced by the bacteria stimulate a large proportion of T cells, leading to streptococcal toxic shock syndrome. Given the rapid clinical progression, effective management of invasive group A streptococcal infections hinges on early recognition of the disease and prompt initiation of supportive care (often intensive care) together with antibacterial therapy. In cases of toxic shock syndrome, it is often difficult to distinguish between streptococcal and staphylococcal infection before cultures become available and so antibacterial choice must include coverage of both of these organisms. In addition, clindamycin is an important adjunctive antibacterial because of its anti-toxin effects and excellent tissue penetration. Early institution of intravenous immunoglobulin therapy should be considered in cases of toxic shock syndrome and severe invasive infection, including necrotizing fasciitis. Early surgical debridement of necrotic tissue is also an important part of management in cases of necrotizing fasciitis.


Necrotizing Fasciitis Toxic Shock Syndrome Acute Rheumatic Fever Scarlet Fever Invasive Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors of this work have no conflicts of interest or funding to disclose.


  1. 1.
    Lamagni TL, Darenberg J, Luca-Harari B, et al. Epidemiology of severe streptococcus pyogenes disease in Europe. J Clin Microbiol 2008 Jul; 46 (7): 2359–67PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    O’Loughlin RE, Roberson A, Cieslak PR, et al. The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000–2004. Clin Infect Dis 2007; 45: 853–62PubMedCrossRefGoogle Scholar
  3. 3.
    Stevens DL. Streptococcal toxic shock syndrome. Clin Microbiol Infect 2002 Mar; 8 (3): 133–6PubMedCrossRefGoogle Scholar
  4. 4.
    Katz AR, Morens DM. Severe streptococcal infections in historical perspective. Clin Infect Dis 1992 Jan; 14 (1): 298–307PubMedCrossRefGoogle Scholar
  5. 5.
    Hribalová V. Streptococcus pyogenes and the toxic shock syndrome. Ann Intern Med 1988 May; 108 (5): 772PubMedCrossRefGoogle Scholar
  6. 6.
    Cone LA, Woodard DR, Schlievert PM, et al. Clinical and bacteriologic observations of a toxic shock-like syndrome due to Streptococcus pyogenes. N Engl J Med 1987 Jul 16; 317: 146–9PubMedCrossRefGoogle Scholar
  7. 7.
    Bartter T, Dascal A, Carroll K, et al. ‘Toxic strep syndrome’: a manifestation of group A streptococcal infection. Arch Intern Med 1988 Jun; 148 (6): 1421–4PubMedCrossRefGoogle Scholar
  8. 8.
    Wheeler MC, Roe MH, Kaplan EL, et al. Outbreak of group A streptococcus septicemia in children: clinical, epidemiologic, and microbiological correlates. Jama 1991 Jul 24–31; 266: 533–7PubMedCrossRefGoogle Scholar
  9. 9.
    Wong VK, Wright Jr HT. Group A beta-hemolytic streptococci as a cause of bacteremia in children. Am J Dis Child 1988 Aug; 142: 831–3PubMedGoogle Scholar
  10. 10.
    Christie CD, Havens PL, Shapiro ED. Bacteremia with group A streptococci in childhood. Am J Dis Child 1988 May; 142 (5): 559–61PubMedGoogle Scholar
  11. 11.
    Lamagni TL. The epidemiology of severe Streptococcus pyogenes disease in Europe. Helsinki: University of Helsinki, 2008Google Scholar
  12. 12.
    Veasy LG, Wiedmeier SE, Orsmond GS, et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 1987 Feb 19; 316: 421–7PubMedCrossRefGoogle Scholar
  13. 13.
    Stevens DL. The flesh-eating bacterium: what’s next?. J Infect Dis 1999 Mar; 179 Suppl. 2: S366–74Google Scholar
  14. 14.
    O’Grady K-A, Kelpie L, Andrews RA, et al. The epidemiology of invasive group A streptococcal disease in Victoria, Australia. Med J Aust 2007; 186: 565–9PubMedGoogle Scholar
  15. 15.
    Carapetis J, Robins-Browne R, Martin D, et al. Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone. Clin Infect Dis 1995 Nov; 21: 1220–7PubMedCrossRefGoogle Scholar
  16. 16.
    Lamagni TL, Efstratiou A, Vuopio-Varkila J, et al. The epidemiology of severe Streptococcus pyogenes associated disease in Europe. Eurosurveillance 2005; 10 (9): 179–84PubMedGoogle Scholar
  17. 17.
    Zakikhany K, Degail MA, Lamagni TL, et al. Increase in invasive Streptococcus pyogenes and Streptococcus pneumoniae infections in England, December 2010 to January 2011. Euro Surveill 2011; 16 (5): 19785PubMedGoogle Scholar
  18. 18.
    Norton R, Smith HV, Wood N, et al. Invasive group A streptococcal disease in North Queensland (1996–2001). Indian J Med Res 2004 May; 119 Suppl.: 148–51PubMedGoogle Scholar
  19. 19.
    Laupland KB, Davies HD, Low DE, et al. Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group. Pediatrics 2000 May; 105 (5): E60Google Scholar
  20. 20.
    Tyrrell GJ, Lovgren M, Kress B, et al. Invasive group A streptococcal disease in Alberta, Canada (2000–2002). J Clin Microbiol 2005; 43: 1678–83PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Kristensen B, Schonheyder HC. A 13-year survey of bacteraemia due to beta-haemolytic streptococci in a Danish county. J Med Microbiol 1995; 43 (1): 63–7PubMedCrossRefGoogle Scholar
  22. 22.
    Siljander T, Lyytikainen O, Vahakuopus S, et al. Rapid emergence of emm84 among invasive Streptococcus pyogenes infections in Finland. J Clin Microbiol 2009 Feb 1; 47 (2): 477–80PubMedCrossRefGoogle Scholar
  23. 23.
    Moses AE, Goldberg S, Korenman Z, et al. Invasive group A streptococcal infections, Israel. Emerg Infect Dis 2002; 8 (4): 421–6PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Vlaminckx BJ, van Pelt W, Schouls LM, et al. Long-term surveillance of invasive group A streptococcal disease in the Netherlands, 1994–2003. Clin Microbiol Infect 2005; 11: 226–31PubMedCrossRefGoogle Scholar
  25. 25.
    Eriksson BK, Norgren M, McGregor K, et al. Group A streptococcal infections in Sweden: a comparative study of invasive and noninvasive infections and analysis of dominant T28 emm28 isolates. Clin Infect Dis 2003 Nov 1; 37 (9): 1189–93PubMedCrossRefGoogle Scholar
  26. 26.
    Eriksson BK, Andersson J, Holm SE, et al. Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome. Clin Infect Dis 1998 Dec; 27 (6): 1428–36PubMedCrossRefGoogle Scholar
  27. 27.
    Steer AC, Jenney AJ, Oppedisano F, et al. High burden of invasive beta-haemolytic streptococcal infections in Fiji. Epidemiol Infect 2008 May; 136 (5): 621–7PubMedCrossRefGoogle Scholar
  28. 28.
    Berkley JA, Lowe BS, Mwangi I, et al. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005 Jan 6; 352 (1): 39–47PubMedCrossRefGoogle Scholar
  29. 29.
    Le Hello S, Doloy A, Baumann F, et al. Clinical and microbial characteristics of invasive Streptococcus pyogenes disease in New Caledonia, a region in Oceania with a high incidence of acute rheumatic fever. J Clin Microbiol 2010 Feb; 48 (2): 526–30PubMedCrossRefGoogle Scholar
  30. 30.
    Hoge CW, Schwartz B, Talkington DF, et al. The changing epidemiology of invasive group A streptococcal infections and the emergence of streptococcal toxic shock-like syndrome: a retrospective population-based study. JAMA 1993 Jan 20; 269: 384–9PubMedCrossRefGoogle Scholar
  31. 31.
    Bisno AL, Rubin FA, Cleary PP, et al. Prospects for a group A streptococcal vaccine: rationale, feasibility, and obstacles. Report of a National Institute of Allergy and Infectious Diseases workshop. Clin Infect Dis 2005 Oct 15; 41 (8): 1150–6PubMedCrossRefGoogle Scholar
  32. 32.
    Laupland KB, Ross T, Church DL, et al. Population-based surveillance of invasive pyogenic streptococcal infection in a large Canadian region. t;. Clin Microbiol Infect 2006; 12: 224–30CrossRefGoogle Scholar
  33. 33.
    Passaro DJ, Smitht DS, Hett EC, et al. Invasive group A streptococcal infections in the San Francisco Bay area, 1989–99. Epidemiol Infect 2002; 129: 471–8PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Andersen MM, Rønne T. Group A streptococcal bacteraemias in Denmark 1987–89. J Infect 1995; 31: 33–7PubMedCrossRefGoogle Scholar
  35. 35.
    Martin PR, Høiby EA. Streptococcal serogroup A epidemic in Norway 1987–1988. Scand J Infect Dis 1990; 22: 421–9PubMedCrossRefGoogle Scholar
  36. 36.
    O’Brien KL, Beall B, Barrett L, et al. Epidemiology of invasive group A streptococcus disease in the United States, 1995–1999. Clin Infect Dis 2002; 35: 268–76PubMedCrossRefGoogle Scholar
  37. 37.
    Carapetis JR, Steer AC, Mulholland EK, et al. The global burden of group A streptococcal diseases. Lancet Infect Dis 2005; 5 (11): 685–94PubMedCrossRefGoogle Scholar
  38. 38.
    Lamagni TL, Neal S, Keshishian C, et al. Predictors of death after severe Streptococcus pyogenes infection. Emerg Infect Dis 2009; 15: 1304–7PubMedCrossRefGoogle Scholar
  39. 39.
    Lamagni TL, Neal S, Keshishian C, et al. Severe Streptococcus pyogenes infections, United Kingdom, 2003–2004. Emerg Infect Dis 2008; 14: 201–9CrossRefGoogle Scholar
  40. 40.
    Steer AC, Jenney AWJ, Kado J, et al. Invasive group A streptococcal disease in Fiji: prospective surveillance 2005–2007. Emerg Infect Dis 2009; 15: 216–22PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Steer AC, Jenney AJ, Oppedisano F, et al. High burden of invasive beta-haemolytic streptococcal infections in Fiji. Epidemiol Infect 2008; 136 (5): 621–7PubMedCrossRefGoogle Scholar
  42. 42.
    Demers B, Simor AE, Vellend H, et al. Severe invasive group A streptococcal infections in Ontario, Canada: 1987–1991. Clin Infect Dis 1993 Jun; 16 (6): 792–800PubMedCrossRefGoogle Scholar
  43. 43.
    Ben Abraham R, Keller N, Vered R, et al. Invasive group A streptococcal infections in a large tertiary center: epidemiology, characteristics and outcome. Infection 2002; 30: 81–5PubMedCrossRefGoogle Scholar
  44. 44.
    Davies HD, McGeer A, Schwartz B, et al. Invasive group A streptococcal infections in Ontario, Canada. Ontario Group A Streptococcal Study Group. N Engl J Med 1996 Aug 22; 335: 547–54Google Scholar
  45. 45.
    Factor SH. Invasive group A streptococcal disease: risk factors for adults. Emerg Infect Dis 2003; 9: 970–7PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008 Oct 1; 198 (7): 962–70PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Tasher D, Stein M, Simões EAF, et al. Invasive bacterial infections in relation to influenza outbreaks, 2006–2010. Clin Infect Dis 2011 Dec 15; 53 (12): 1199–207PubMedCrossRefGoogle Scholar
  48. 48.
    Lamagni TL, Neal S, Keshishian C, et al. Epidemic of severe Streptococcus pyogenes infections in injecting drug users in the UK, 2003–2004. Clin Microbiol Infect 2008; 4: 1002–9CrossRefGoogle Scholar
  49. 49.
    Navarro VJ, Axelrod PI, Pinover W, et al. A comparison of Streptococcus pyogenes (group A streptococcal) bacteremia at an urban and a suburban hospital; the importance of intravenous drug use. Arch Intern Med 1993; 153: 2679–84PubMedCrossRefGoogle Scholar
  50. 50.
    Sierra J, Sánchez F, Castro P, et al. Group A streptococcal infections in injection drug users in Barcelona, Spain: epidemiologic, clinical, and microbiologic analysis of 3 clusters of cases from 2000 to 2003. Medicine (Baltimore) 2006; 85: 139–46CrossRefGoogle Scholar
  51. 51.
    Doctor A, Harper MB, Fleisher GR. Group A beta-hemolytic streptococcal bacteremia: historical overview, changing incidence, and recent association with varicella. Pediatrics 1995 Sep; 96 (3 Pt 1): 428–33Google Scholar
  52. 52.
    Falcone PA, Pricolo VE, Edstrom LE. Necrotizing fasciitis as a complication of chickenpox. Clin Pediatr (Phila) 1988 Jul; 27 (7): 339–43CrossRefGoogle Scholar
  53. 53.
    Vugia DJ, Peterson CL, Meyers HB, et al. Invasive group A streptococcal infections in children with varicella in Southern California. Pediatr Infect Dis J 1996 Feb; 15: 146–50PubMedCrossRefGoogle Scholar
  54. 54.
    Brogan TV, Nizet V, Waldhausen JH, et al. Group A streptococcal necrotizing fasciitis complicating primary varicella: a series of fourteen patients. Pediatr Infect Dis J 1995 Jul; 14 (7): 588–94PubMedCrossRefGoogle Scholar
  55. 55.
    Wilson GJ, Talkington DF, Gruber W, et al. Group A streptococcal necrotizing fasciitis following varicella in children: case reports and review. Clin Infect Dis 1995 May; 20 (5): 1333–8PubMedCrossRefGoogle Scholar
  56. 56.
    Zerr DM, Alexander ER, Duchin JS, et al. A case-control study of necrotizing fasciitis during primary varicella. Pediatrics 1999 Apr; 103: 783–90PubMedCrossRefGoogle Scholar
  57. 57.
    Cowan MR, Primm PA, Scott SM, et al. Serious group A beta-hemolytic streptococcal infections complicating varicella. Ann Emerg Med 1994 Apr; 23 (4): 818–22PubMedCrossRefGoogle Scholar
  58. 58.
    Bradley JS, Schlievert PM, Sample Jr TG. Streptococcal toxic shock-like syndrome as a complication of varicella. Pediatr Infect Dis J 1991 Jan; 10 (1): 77–9PubMedCrossRefGoogle Scholar
  59. 59.
    Tyrrell GJ, Lovgren M, Kress B, et al. Varicella-associated group A streptococcal disease in Alberta, Canada 2000–2002. Clin Infect Dis 2005; 40: 1055–7PubMedCrossRefGoogle Scholar
  60. 60.
    Chuang I, Van Beneden C, Beall B, et al. Network ABC-SEIP. Population-based surveillance for postpartum invasive group A Streptococcus infections, 1995–2000. Clin Infect Dis 2002 Sep 15; 35 (6): 665–70PubMedGoogle Scholar
  61. 61.
    Deutscher M, Lewis M, Zell ER, et al. Incidence and severity of invasive Streptococcus pneumoniae, group A Streptococcus, and group B Streptococcus infections among pregnant and postpartum women. Clin Infect Dis 2011 Jul 15; 53 (2): 114–23PubMedCrossRefGoogle Scholar
  62. 62.
    Khan KS, Wojdyla D, Say L, et al. WHO analysis of causes of maternal death: a systematic review. Lancet 2006 Apr 1; 367 (9516): 1066–74PubMedCrossRefGoogle Scholar
  63. 63.
    Centre for Maternal and Child Enquiries and Royal College of Obstetricians and Gynaecologists. CMACE/RCOG joint guideline: management of women with obesity in pregnancy. 2010 Mar [online]. Available from URL: [Accessed 2012 Feb 1]
  64. 64.
    Miyairi I, Berlingieri D, Protic J, et al. Neonatal invasive group A streptococcal disease: case report and review of the literature. Pediatr Infect Dis J 2004; 23 (2): 161–5PubMedCrossRefGoogle Scholar
  65. 65.
    Mahieu LM, Holm SE, Goossens HJ, et al. Congenital streptococcal toxic shock syndrome with absence of antibodies against streptococcal pyrogenic exotoxins. J Pediatr 1995 Dec; 127 (6): 987–9PubMedCrossRefGoogle Scholar
  66. 66.
    Health Protection Agency Group A Streptococcus Working Group. Interim UK guidelines for management of close community contacts of invasive group A streptococcal disease. Commun Dis Public Health 2004; 7: 354–61Google Scholar
  67. 67.
    Curtis N. Invasive group A streptococcal infection. Curr Opin Infect Dis 1996; 9: 191–2CrossRefGoogle Scholar
  68. 68.
    Fischetti VA. Streptococcal M protein: molecular design and biological behavior. Clin Microbiol Rev 1989 Jul; 2: 285–314PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Cunningham MW. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 2000 Jul; 13: 470–511PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Hasty DL, Ofek I, Courtney HS, et al. Multiple adhesins of streptococci. Infection and Immunity 1992; 60 (6): 2147–52PubMedPubMedCentralGoogle Scholar
  71. 71.
    Horstmann RD, Sievertsen HJ, Leippe M, et al. Role of fibrinogen in complement inhibition by streptococcal M protein. Infect Immun 1992 Dec; 60: 5036–41PubMedPubMedCentralGoogle Scholar
  72. 72.
    Wessels MR, Moses AE, Goldberg JB, et al. Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci. Proc Natl Acad Sci U S A 1991; 88: 8317–21PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Ji Y, McLandsborough L, Kondagunta A, et al. C5a peptidase alters clearance and trafficking of group A streptococci by infected mice. Infect Immun 1996 Feb; 64 (2): 503–10PubMedPubMedCentralGoogle Scholar
  74. 74.
    Proft T, Sriskandan S, Yang L, et al. Superantigens and streptococcal toxic shock syndrome. Emerg Infect Dis 2003 Oct; 9 (10): 1211–8PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Llewelyn M, Cohen J. Superantigens: microbial agents that corrupt immunity. Lancet Infect Dis 2002 Mar, 2 (3): 156–62Google Scholar
  76. 76.
    Curtis N. Kawasaki disease and toxic shock syndrome: at last the etiology is clear?. Adv Exp Med Biol 2004; 549: 191–200PubMedCrossRefGoogle Scholar
  77. 77.
    Kotb M. Bacterial pyrogenic exotoxins as superantigens. Clin Microbiol Rev 1995 Jul; 8 (3): 411–26PubMedPubMedCentralGoogle Scholar
  78. 78.
    Petersson K, Forsberg G, Walse B. Interplay between superantigens and immunoreceptors. Scand J Immunol 2004 Apr; 59 (4): 345–55PubMedCrossRefGoogle Scholar
  79. 79.
    Dinges MM, Orwin PM, Schlievert PM. Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 2000 Jan; 13 (1): 16–34PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Miethke T, Wahl C, Heeg K, et al. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J Exp Med 1992 Jan 1; 175 (1): 91–8PubMedCrossRefGoogle Scholar
  81. 81.
    Facklam R, Beall B, Efstratiou A, et al. emm typing and validation of provisional M types for group A streptococci. Emerg Infect Dis 1999; 5 (2): 247–53PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Steer AC, Law I, Matatolu L, et al. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis 2009; 9: 611–6PubMedCrossRefGoogle Scholar
  83. 83.
    HPA. Group A streptococcal infections: fourth update on seasonal activity, 2008/09. Health Protection Report. 2009 [online]. Available from URL: [Accessed 2012 Feb 1]
  84. 84.
    Holm SE, Norrby A, Bergholm AM, et al. Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988–1989. J Infect Dis 1992; 166: 31–7PubMedCrossRefGoogle Scholar
  85. 85.
    Rogers S, Commons R, Danchin MH, et al. Strain prevalence, rather than innate virulence potential, is the major factor responsible for an increase in serious group a streptococcus infections. J Infect Dis 2007 Jun 1; 195 (11): 1625–33PubMedCrossRefGoogle Scholar
  86. 86.
    Shea PR, Beres SB, Flores AR, et al. Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations. Proc Natl Acad Sci U S A 2011 Mar 22; 108 (12): 5039–44PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Bessen DE, Carapetis JR, Beall B, et al. Contrasting molecular epidemiology of group A streptococci causing tropical and nontropical infections of the skin and throat. J Infect Dis 2000 Oct; 182: 1109–16PubMedCrossRefGoogle Scholar
  88. 88.
    Chelsom J, Halstensen A, Haga T, et al. Necrotising fasciitis due to group A streptococci in western Norway: incidence and clinical features. Lancet 1994 Oct 22; 344: 1111–5PubMedCrossRefGoogle Scholar
  89. 89.
    Giuliano A, Lewis Jr F, Hadley K, et al. Bacteriology of necrotizing fasciitis. Am J Surg 1977 Jul; 134 (1): 52–7PubMedCrossRefGoogle Scholar
  90. 90.
    Wall DB, de Virgilio C, Black S, et al. Objective criteria may assist in distinguishing necrotizing fasciitis from nonnecrotizing soft tissue infection. Am J Surg 2000 Jan; 179 (1): 17–21PubMedCrossRefGoogle Scholar
  91. 91.
    Kaul R, McGeer A, Low DE, et al. Population-based surveillance for group A streptococcal necrotizing fasciitis: clinical features, prognostic indicators, and microbiologic analysis of seventy-seven cases. Ontario Group A Streptococcal Study. Am J Med 1997 Jul; 103 (1): 18–24Google Scholar
  92. 92.
    Dahl PR, Perniciaro C, Holmkvist KA, et al. Fulminant group A streptococcal necrotizing fasciitis: clinical and pathologic findings in 7 patients. J Am Acad Dermatol 2002 Oct; 47 (4): 489–92PubMedCrossRefGoogle Scholar
  93. 93.
    Ward RG, Walsh MS. Necrotizing fasciitis: 10 years’ experience in a district general hospital. Br J Surg 1991 Apr; 78: 488–9PubMedCrossRefGoogle Scholar
  94. 94.
    Stevens DL. Streptococcal toxic-shock syndrome: spectrum of disease, pathogenesis, and new concepts in treatment. Emerg Infect Dis 1995 Jul-Sep; 1: 69–78PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Stevens DL. Invasive group A streptococcus infections. Clin Infect Dis 1992 Jan; 14: 2–11PubMedCrossRefGoogle Scholar
  96. 96.
    Kevy SV, Lowe BA. Streptococcal pneumonia and empyema in childhood. N Engl J Med 1961; 264: 738–43PubMedCrossRefGoogle Scholar
  97. 97.
    Brothers TE, Tagge DU, Stutley JE, et al. Magnetic resonance imaging differentiates between necrotizing and non-necrotizing fasciitis of the lower extremity. J Am Coll Surg 1998 Oct; 187 (4): 416–21PubMedCrossRefGoogle Scholar
  98. 98.
    Zittergruen M, Grose C. Magnetic resonance imaging for early diagnosis of necrotizing fasciitis. Pediatr Emerg Care 1993 Feb; 9 (1): 26–8PubMedCrossRefGoogle Scholar
  99. 99.
    Schmid MR, Kossmann T, Duewell S. Differentiation of necrotizing fasciitis and cellulitis using MR imaging. AJR Am J Roentgenol 1998 Mar; 170 (3): 615–20PubMedCrossRefGoogle Scholar
  100. 100.
    Stamenkovic I, Lew PD. Early recognition of potentially fatal necrotizing fasciitis: the use of frozen-section biopsy. N Engl J Med 1984 Jun 28; 310 (26): 1689–93PubMedCrossRefGoogle Scholar
  101. 101.
    Wong CH, Wang YS. The diagnosis of necrotizing fasciitis. Curr Opin Infect Dis 2005 Apr; 18 (2): 101–6PubMedCrossRefGoogle Scholar
  102. 102.
    Wong CH, Khin LW, Heng KS, et al. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med 2004 Jul; 32 (7): 1535–41PubMedCrossRefGoogle Scholar
  103. 103.
    No authors listed. Defining the group A streptococcal toxic shock syndrome: rationale and consensus definition. The Working Group on Severe Streptococcal Infections. JAMA 1993 Jan 20; 269: 390–1Google Scholar
  104. 104.
    Reingold AL, Hargrett NT, Shands KN, et al. Toxic shock syndrome surveillance in the United States, 1980 to 1981. Ann Intern Med 1982 Jun; 96 (6 Pt 2): 875–80PubMedCrossRefGoogle Scholar
  105. 105.
    Catena F, La Donna M, Ansaloni L, et al. Necrotizing fasciitis: a dramatic surgical emergency. Eur J Emerg Med 2004; 11 (1): 44–8PubMedCrossRefGoogle Scholar
  106. 106.
    Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am 1996 Dec; 10 (4): 727–46PubMedCrossRefGoogle Scholar
  107. 107.
    Mulla ZD, Leaverton PE, Wiersma ST. Invasive group A streptococcal infections in Florida. South Med J 2003; 96 (10): 968–73PubMedCrossRefGoogle Scholar
  108. 108.
    Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J 1999 Dec; 18 (12): 1096–100PubMedCrossRefGoogle Scholar
  109. 109.
    Stevens DL, Gibbons AE, Bergstrom R, et al. The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. J Infect Dis 1988 Jul; 158: 23–8PubMedCrossRefGoogle Scholar
  110. 110.
    Mascini EM, Jansze M, Schouls LM, et al. Penicillin and clindamycin differentially inhibit the production of pyrogenic exotoxins A and B by group A streptococci. Int J Antimicrob Agents 2001; 18: 395–8PubMedCrossRefGoogle Scholar
  111. 111.
    Sriskandan S, McKee A, Hall L, et al. Comparative effects of clindamycin and ampicillin on superantigenic activity of Streptococcus pyogenes. J Antimicrob Chemother 1997; 40 (2): 275–7PubMedCrossRefGoogle Scholar
  112. 112.
    Herbert S, Barry P, Novick RP. Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus. Infect Immun 2001; 69 (5): 2996–3003PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Gemmell CG, Peterson PK, Schmeling D, et al. Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin. J Clin Invest 1981 May; 67 (5): 1249–56PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Craig WA, Vogelman B. The postantibiotic effect. Ann Intern Med 1987 Jun; 106 (6): 900–2PubMedCrossRefGoogle Scholar
  115. 115.
    Wong CH, Chang HC, Pasupathy S, et al. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am 2003 Aug; 85-A (8): 1454-60Google Scholar
  116. 116.
    Bilton BD, Zibari GB, McMillan RW, et al. Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study. Am Surg 1998 May; 64 (5): 397–400PubMedGoogle Scholar
  117. 117.
    Norrby-Teglund A, Muller MP, Mcgeer A, et al. Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach. Scand J Infect Dis 2005; 37 (3): 166–72PubMedCrossRefGoogle Scholar
  118. 118.
    Muller MP, McGeer A, Low DE, Ontario Group A Streptococcal Study. Successful outcome in six patients treated conservatively for suspected necrotizing fasciitis (NF) due to group A streptococcus (GAS) [abstract]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, 2001 Dec 16–19; Chicago (IL)Google Scholar
  119. 119.
    Alejandria MM, Lansang MA, Dans LF, et al. Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev 2002; (1): CD001090Google Scholar
  120. 120.
    Werdan K. Intravenous immunoglobulin for prophylaxis and therapy of sepsis. Curr Opin Crit Care 2001 Oct; 7 (5): 354–61PubMedCrossRefGoogle Scholar
  121. 121.
    Norrby-Teglund A, Kaul R, Low DE, et al. Evidence for the presence of streptococcal-superantigen-neutralizing antibodies in normal polyspecific immunoglobulin G. Infect Immun 1996; 64: 5395–8PubMedPubMedCentralGoogle Scholar
  122. 122.
    Norrby-Teglund A, Kaul R, Low DE, et al. Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production. J Immunol 1996; 156: 3057–64PubMedGoogle Scholar
  123. 123.
    Andersson U, Chauvet JM, Skansen-Saphir U, et al. Pooled human IgG modulates cytokine production in lymphocytes and monocytes. J Immunol Methods 1994; 175: 201–13PubMedCrossRefGoogle Scholar
  124. 124.
    Darenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003 Aug 1; 37: 333–40PubMedCrossRefGoogle Scholar
  125. 125.
    Kaul R, McGeer A, Norrby-Teglund A, et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome: a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis 1999; 28: 800–7CrossRefGoogle Scholar
  126. 126.
    Shah SS, Hall M, Srivastava R, et al. Intravenous immunoglobulin in children with streptococcal toxic shock syndrome. Clin Infect Dis 2009; 49: 1369–76PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Valiquette L, Low DE, McGeer AJ. Assessing the impact of intravenous immunoglobulin in the management of streptococcal toxic shock syndrome: a noble but difficult quest. Clin Infect Dis 2009; 49: 1377–9PubMedCrossRefGoogle Scholar
  128. 128.
    Orbach H, Katz U, Sherer Y, et al. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol 2005; 29 (3): 173–84PubMedCrossRefGoogle Scholar
  129. 129.
    Curtis N. Non-steroidal anti-inflammatory drugs may predispose to invasive group A streptococcal infections. Arch Dis Child 1996 Dec; 75 (6): 547Google Scholar
  130. 130.
    Zerr DM, Rubens CE. NSAIDS and necrotizing fasciitis. Pediatr Infect Dis J 1999 Aug; 18 (8): 724–5PubMedCrossRefGoogle Scholar
  131. 131.
    Stevens DL. Could nonsteroidal antiinflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome?. Clin Infect Dis 1995 Oct; 21 (4): 977–80PubMedCrossRefGoogle Scholar
  132. 132.
    Ford LM, Waksman J. Necrotizing fasciitis during primary varicella. Pediatrics 2000 Jun; 105 (6): 1372–3; author reply 1373–5PubMedCrossRefGoogle Scholar
  133. 133.
    Lesko SM, O’Brien KL, Schwartz B, et al. Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella. Pediatrics 2001 May; 107 (5): 1108–15PubMedCrossRefGoogle Scholar
  134. 134.
    Forbes N, Rankin AP. Necrotizing fasciitis and non steroidal anti-inflammatory drugs: a case series and review of the literature. N Z Med J 2001 Jan 26; 114 (1124): 3–6PubMedGoogle Scholar
  135. 135.
    Rimailho A, Riou B, Richard C, et al. Fulminant necrotizing fasciitis and nonsteroidal anti-inflammatory drugs. J Infect Dis 1987 Jan; 155 (1): 143–6PubMedCrossRefGoogle Scholar
  136. 136.
    Brun-Buisson CJ, Saada M, Trunet P, et al. Haemolytic streptococcal gangrene and non-steroidal anti-inflammatory drugs. Br Med J (Clin Res Ed) 1985 Jun 15; 290 (6484): 1786Google Scholar
  137. 137.
    Krige JE, Spence RA, Potter PC, et al. Necrotising fasciitis after diflunisal for minor injury. Lancet 1985 Dec 21–28; 2 (8469–70): 1432–3Google Scholar
  138. 138.
    Cockerill 3rd FR. An outbreak of invasive group A streptococcal disease associated with high carriage rates of the invasive clone among school-aged children[comment]. Pediatrics 1998; 101: 136–40CrossRefGoogle Scholar
  139. 139.
    Huang YC, Hsueh PR, Lin TY, et al. A family cluster of streptococcal toxic shock syndrome in children: clinical implication and epidemiological investigation. Pediatrics 2001 May; 107 (5): 1181–3PubMedCrossRefGoogle Scholar
  140. 140.
    Schwartz B, Elliott JA, Butler JC, et al. Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings. Clin Infect Dis 1992 Aug; 15 (2): 277–84PubMedCrossRefGoogle Scholar
  141. 141.
    Gamba MA, Martinelli M, Schaad HJ, et al. Familial transmission of a serious disease-producing group A streptococcus clone: case reports and review. Clin Infect Dis 1997 Jun; 24 (6): 1118–21PubMedCrossRefGoogle Scholar
  142. 142.
    Stromberg A, Romanus V, Burman LG. Outbreak of group A streptococcal bacteremia in Sweden: an epidemiologic and clinical study. J Infect Dis 1991 Sep; 164 (3): 595–8PubMedCrossRefGoogle Scholar
  143. 143.
    Auerbach SB, Schwartz B, Williams D, et al. Outbreak of invasive group A streptococcal infections in a nursing home: lessons on prevention and control. Arch Intern Med 1992 May; 152 (5): 1017–22PubMedCrossRefGoogle Scholar
  144. 144.
    Public Health Agency for Canada. Guidelines for the prevention and control of invasive group A streptococcal diseases. Can Commun Dis Rep 2006; S2 (32): 1–26Google Scholar
  145. 145.
    Robinson KA, Rothrock G, Phan Q, et al. Risk for severe group A streptococcal disease among patients’ household contacts. Emerg Infect Dis 2003 Apr; 9: 443–7PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Prevention of Invasive Group A Streptococcal Infections Workshop Participants. Prevention of invasive group A streptococcal disease among household contacts of case patients and among postpartum and postsurgical patients: recommendations from the Centers for Disease Control and Prevention [published erratum appears in Clin Infect Dis 2003 Jan 15; 36 (2): 243]. Clin Infect Dis 2002 Oct 15; 35: 950–9CrossRefGoogle Scholar
  147. 147.
    Carapetis JR. Current issues in managing group A streptococcal infections. Adv Exp Med Biol 2004; 549: 185–90PubMedCrossRefGoogle Scholar
  148. 148.
    Smith A, Lamagni TL, Oliver I, et al. Invasive group A streptococcal disease: should close contacts routinely receive antibiotic prophylaxis?. Lancet Infect Dis 2005; 5 (8): 494–500PubMedCrossRefGoogle Scholar
  149. 149.
    Daneman N, Green KA, Low DE, et al. Surveillance for hospital outbreaks of invasive group a streptococcal infections in Ontario, Canada, 1992 to 2000. Ann Intern Med 2007; 147: 234–41PubMedCrossRefGoogle Scholar
  150. 150.
    Ministere de la Sante et des Solidarites. Comite technique des infections nosocomiales et des infections liees aus soins. Guide pour la prevention et l’investigation des infections hospitalieres a Streptococcus pyogenes. Paris: Ministere de la Sante et des Solidarites, 2006Google Scholar
  151. 151.
    Health Protection Surveillance Centre. Invasive group A streptococcus sub-committee. The management of invasive group A streptococcal infections in Ireland. Dublin: HPSC, 2006Google Scholar
  152. 152.
    Steer JA, Lamagni T, Healy B, et al. Guidelines for prevention and control of group A streptococcal infection in acute healthcare and maternity settings in the UK. J Infect 2012 Jan; 64 (1): 1–18PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Andrew C. Steer
    • 1
    • 2
    • 3
    Email author
  • Theresa Lamagni
    • 4
  • Nigel Curtis
    • 2
    • 3
  • Jonathan R. Carapetis
    • 5
  1. 1.Centre for International Child Health, Department of PaediatricsThe University of Melbourne, Royal Children’s HospitalParkvilleAustralia
  2. 2.Infectious Diseases Unit, Department of General MedicineRoyal Children’s Hospital MelbourneParkvilleAustralia
  3. 3.Murdoch Children’s Research InstituteParkvilleAustralia
  4. 4.Health Protection AgencyLondonUK
  5. 5.Menzies School of Health Research and Charles Darwin UniversityDarwinAustralia

Personalised recommendations