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Toxic Shock Syndrome Treatment & Management

  • Author: Ramesh Venkataraman, MBBS; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
 
Updated: Apr 16, 2015
 

Medical Care

TSS has a rapid, dramatic, and fulminant onset. Quick recognition of the syndrome is important for enabling appropriate and prompt treatment. S pyogenes continues to be susceptible to beta-lactam antibiotics. Although very effective in treating pharyngitis and other superficial infections, aggressive GAS infections do not respond well to penicillin and continue to be associated with high mortality rates and extensive morbidity.

The principles in the management of septic shock in general must be instituted as soon as possible (see Septic Shock). These include the following components:

  • Early recognition
  • Early and adequate antibiotic therapy
  • Source control and early debridement of infected/necrotic wounds
  • Early hemodynamic resuscitation and continued support
  • Corticosteroids (refractory vasopressor-dependent shock)
  • Drotrecogin alpha (Severely ill if APACHE II >25) within 24 hours of onset of first organ dysfunction
  • Tight glycemic control (Glucose target of < 180 mg/dL are considered to be adequate based on present data.)
  • Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS) with maintenance of plateau pressures of less than 30 cm of water.

In experimental models of S pyogenes infection, penicillin proved to be inferior to clindamycin. The physiologic state of the organism attributed to the inoculum effects is suggested as the mechanism of failure.

Penicillin and other beta-lactam antibiotics are most efficacious against rapidly growing bacteria; therefore, these antibiotics have the greatest efficacy when organisms are growing rapidly during the early stages of infection or in mild infections. When higher concentrations of GAS accumulate (eg, deep-seeded infections), the effectiveness of beta-lactam antibiotics decreases because the bacterial growth slows (stationary phase).

Penicillin mediates its antibacterial action against GAS by interacting with penicillin-binding proteins (PBPs). Experimentally, the binding of penicillin has been shown to decrease in stationary cells, related to cells in the logarithmic growth phase; thus, the loss of certain PBPs during the stationary growth phase may be secondary to the inoculum effect and may account for penicillin failure.

Clindamycin has multiple effects against GAS infection. The efficacy of clindamycin is not affected by inoculum size or growth stage; furthermore, this agent is a potent suppressor of bacterial toxin synthesis. Clindamycin facilitates phagocytosis of S pyogenes by inhibiting M protein synthesis. Clindamycin suppresses synthesis of PBPs, which also are enzymes involved in cell wall synthesis. Clindamycin has a longer postantibiotic effect than penicillin. Clindamycin causes suppression of lipopolysaccharide-induced monocyte synthesis of TNF.[15]

Dixit et al reported successful treatment of a case of recurrent menstrual TSS after tampons were discontinued with rifampicin and clindamycin.[16]

The FDA recently approved 3 new antibiotics, oritavancin Orbactiv), dalbavancin (Dalvance), and tedizolid (Sivextro), for the treatment of acute bacterial skin and skin structure infections. These agents are active against Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MSSA, MRSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), among others. For complete drug information, including dosing, see the following monographs:

Recommended antibiotic therapy

For patients with GAS infection, the administration of clindamycin (600 mg -900 mg IV q8h) is recommended. Other clinicians recommend combined therapy, in which penicillin G (4 million U IV q4h) is combined with clindamycin.

Because differentiating between STSS and streptococcal TSS on clinical grounds alone is difficult, intravenous penicillin also should be administered in addition to a beta-lactamase resistant antibiotic until a bacteriologic diagnosis is confirmed by culture. Alternatively, a first-generation cephalosporin or vancomycin can be used.

Staphylococcal toxic shock syndrome

Large doses of a beta-lactamase–resistant, antistaphylococcal, antimicrobial agent should be administered intravenously to patients with staphylococcal infections. The usually prescribed antibiotics are nafcillin, oxacillin, and first generation cephalosporin. Nafcillin or oxacillin (2 g q4h) is generally recommended. Vancomycin can be used in penicillin-allergic patients.

These agents have been known to increase TSST-1 in culture possibly by cell lysis. Therefore, clindamycin may be used in combination for the first few days to reduce synthesis of TSST-1.

The antibiotic treatment is continued for 10 to 14 days in absence of a complication.

Intravenous fluids

TSS causes intractable hypotension and diffuse capillary leak; therefore, massive amounts of intravenous fluids (10-15 L/d) often are necessary. Patients in shock may require central venous monitoring or right heart catheterization to guide fluid management.

The patient's blood pressure may improve with administration of fluids alone; otherwise, vasopressors (eg, dopamine) or even more potent vasoconstrictors (eg, norepinephrine) are required. Norepinephrine with or without dobutamine may be more effective than high-dose dopamine or epinephrine to preserve splanchnic perfusion.

Patients with TSS will require supportive measures, including intubation and mechanical ventilation, dialysis in patients who have developed renal failure, and adequate nutritional support.

Other treatment measures

Intravenous immunoglobulin

Several anecdotal reports, 1 large series of 21 patients and a case control study, reported lower mortality rates for patients with Streptococcal TSS treated with intravenous immunoglobulins.[11, 17, 18] Intravenous immunoglobulins also have been reported to be beneficial in severe cases of Staphylococcal TSS. A single dose of IVIG (400 mg/kg), generates protective levels of antibody to TSST-1 that persist for week. The recommended initial dosage is 2 g/kg, followed by 0.4 g/kg for as long as 5 days.

The mechanism responsible for the efficacy of gamma-globulin therapy may be neutralization of the circulating toxins, inhabitation of TNF-alpha production via nonspecific inhabitation of monocyte or T-cell activation, or inhibition of other streptococcal virulence factors. The contraindications include a history of anaphylaxis from immune globulin in past, immunoglobulin A (IgA) deficiency, and circulating anti-IgA antibodies.[19]

A recent case series described 7 patients with severe soft tissue infection caused by GAS and toxic shock syndrome. All were treated with effective antimicrobials and high-dose intravenous immune serum globulin (IVIG). Surgery was either not performed or only limited exploration was carried out. Six of the patients had toxic shock syndrome. The study suggests that the use of a medical regimen including IVIG in patients with severe GAS soft tissue infections may allow a minimally invasive approach. This can limit the need to perform immediate wide debridements and amputations in unstable patients.[20]

Another prospective, randomized, controlled study included patients with severe sepsis and septic shock of intra-abdominal origin admitted to the ICU. Polyvalent IgM-enriched immunoglobulin (Ig) (Pentaglobin; IVIG group) at a dosage of 7 mL/kg/day for 5 days or an equal amount of 5% human albumin (control group) was randomized. Fifty-six patients were enrolled. The overall mortality rate was 37.5%. In the intent-to-treat analysis, the mortality rate was reduced from 48.1% in patients treated with antibiotic plus albumin to 27.5% for patients with antibiotic plus IVIG. IVIG administration in combination with adequate antibiotics improved the survival of surgical ICU patients with intra-abdominal sepsis.[21]

Others

Hyperbaric oxygen has been used anecdotally in few patients, but whether this treatment is useful is not clear.

High-dose corticosteroid therapy has not been shown to be beneficial; stress-dose steroids (hydrocortisone 50 mg IV every 6 hours) should be considered in patients with refractory shock despite adequate antimicrobial theory and source control.

In recent years, research is continuing to develop either monoclonal antibodies against TSST-1 or other peptides to block the ability of bacterial toxins to activate T cells, therefore blocking the toxicity cascade.[22] Most of this research presently is focused on in vitro and animal models of toxic shock.

Guidelines

The Infectious Diseases Society of America recently updated their guidelines for the diagnosis and management of skin and soft tissue infections. For the full guidelines, see Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.[23, 24]

Additional guides from the Surviving Sepsis Campaign Committee have also been updated. See Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.[25]

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Surgical Care

Prompt, aggressive exploration and debridement of patients thought to have deep-seeded pyogenic infection constitutes a surgical emergency. Surgical exploration through a small incision with visualization of the muscle and fascia may provide an early and definitive diagnosis of necrotizing fasciitis. Infection often is more extensive than is apparent from external examination. Surgical debridement of infected tissue is extremely important and often requires re-exploration to ensure adequacy of resection.

See the images below.

Extensive debridement of necrotizing fasciitis of Extensive debridement of necrotizing fasciitis of the hand.
The hand is healing following aggressive surgical The hand is healing following aggressive surgical debridement of necrotizing fasciitis of the hand (see Image 15).
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Consultations

Consultation with a surgeon should occur early.

A consultation with an infectious diseases specialist is mandatory, and a consultation with an intensivist also is required for management of these patients in an intensive care unit.

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Contributor Information and Disclosures
Author

Ramesh Venkataraman, MBBS Consultant, Critical Care Medicine, Apollo Hospitals, India

Ramesh Venkataraman, MBBS is a member of the following medical societies: American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, Society of Critical Care Medicine, Indian Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM is a member of the following medical societies: American College of Chest Physicians, Association of University Anesthetists, European Society of Intensive Care Medicine, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Shock Society, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Additional Contributors

Cory Franklin, MD Professor, Department of Medicine, Chicago Medical School at Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital

Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthors Godfrey Harding, MD, FRCP(C), and Ken Dolynchuk, MD, PhD, FRCSC, to the development and writing of this article.

References
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  3. Davis JP, Chesney PJ, Wand PJ. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med. 1980 Dec 18. 303(25):1429-35. [Medline].

  4. Ellies E, Vallée F, Mari A, Silva S, Bauriaud R, Fourcade O, et al. [Toxic shock syndrome consecutive to the presence of vaginal tampon for menstruation regressive after early haemodynamic optimization and activated protein C infusion]. Ann Fr Anesth Reanim. 2009 Jan. 28(1):91-5. [Medline].

  5. Cone LA, Woodard DR, Schlievert PM. Clinical and bacteriologic observations of a toxic shock-like syndrome due to Streptococcus pyogenes. N Engl J Med. 1987 Jul 16. 317(3):146-9. [Medline].

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  8. Davies HD, McGeer A, Schwartz B. Invasive group A streptococcal infections in Ontario, Canada. Ontario Group A Streptococcal Study Group. N Engl J Med. 1996 Aug 22. 335(8):547-54. [Medline].

  9. Eriksson BK, Andersson J, Holm SE. Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome. Clin Infect Dis. 1998 Dec. 27(6):1428-36. [Medline].

  10. Stevens DL. Invasive group A streptococcus infections. Clin Infect Dis. 1992 Jan. 14(1):2-11. [Medline].

  11. Demers B, Simor AE, Vellend H. Severe invasive group A streptococcal infections in Ontario, Canada: 1987-1991. Clin Infect Dis. 1993 Jun. 16(6):792-800; discussion 801-2. [Medline].

  12. Matsuda Y, Kato H, Ono E, Kikuchi K, Muraoka M, Takagi K, et al. Diagnosis of toxic shock syndrome by two different systems; clinical criteria and monitoring of TSST-1-reactive T cells. Microbiol Immunol. 2008 Nov. 52(11):513-21. [Medline].

  13. The Working Group on Severe Streptococcal Infections. Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. JAMA. 1993 Jan 20. 269(3):390-1. [Medline].

  14. Park JS, Kim JS, Yi J, Kim EC. [Production and characterization of anti-staphylococcal toxic shock syndrome toxin-1 monoclonal antibody]. Korean J Lab Med. 2008 Dec. 28(6):449-56. [Medline].

  15. Kalyan S, Chow AW. Staphylococcal toxic shock syndrome toxin-1 induces the translocation and secretion of high mobility group-1 protein from both activated T cells and monocytes. Mediators Inflamm. 2008. 2008:512196. [Medline].

  16. Dixit S, Fischer G, Wittekind C. Recurrent menstrual toxic shock syndrome despite discontinuation of tampon use: Is menstrual toxic shock syndrome really caused by tampons?. Australas J Dermatol. 2012 Aug 17. [Medline].

  17. Kaul R, McGeer A, Norrby-Teglund A. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis. 1999 Apr. 28(4):800-7. [Medline].

  18. Stevens DL. The flesh-eating bacterium: what's next?. J Infect Dis. 1999 Mar. 179 Suppl 2:S366-74. [Medline].

  19. Breshears LM, Schlievert PM, Peterson ML. A disintegrin and metalloproteinase 17 (ADAM17) and epidermal growth factor receptor (EGFR) signaling drive the epithelial response to Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1). J Biol Chem. 2012 Sep 21. 287(39):32578-87. [Medline]. [Full Text].

  20. Norrby-Teglund A, Muller MP, Mcgeer A. 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):166-72. [Medline].

  21. Rodríguez A, Rello J, Neira J, Maskin B, Ceraso D, Vasta L. Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery. Shock. 2005 Apr. 23(4):298-304. [Medline].

  22. Karauzum H, Chen G, Abaandou L, et al. Synthetic human monoclonal antibodies toward staphylococcal enterotoxin B (SEB) protective against toxic shock syndrome. J Biol Chem. 2012 Jul 20. 287(30):25203-15. [Medline]. [Full Text].

  23. [Guideline] Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014 Jul 15. 59(2):147-59. [Medline].

  24. Barclay L. IDSA: skin and soft tissue infections guidelines updated. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827399. Accessed: August 22, 2014.

  25. [Guideline] Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb. 41(2):580-637. [Medline].

 
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Description of M proteins and streptococcal toxins.
Group A streptococci cause beta hemolysis on blood agar.
Group A streptococci on Gram stain of blood isolated from a patient who developed toxic shock syndrome. Courtesy of T. Matthews.
This schematic shows interaction among T-cell receptor, superantigen, and class II major histocompatability complex. The binding of superantigen to class II molecules and T-cell receptors is not limited by antigen specificity and lies outside the normal antigen binding sites.
Progression of soft tissue swelling to vesicle or bullous formation is an ominous sign and suggests streptococcal shock syndrome. Courtesy of S. Manocha.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The leg was incised to exclude underlying necrotizing infection. Courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. This patient also had streptococcal pharyngitis. Courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteristic feature of the syndrome. Courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteristic feature of the syndrome. The patient improved with antibiotics and intravenous gammaglobulin therapy. Several days later, a characteristic desquamation of the skin occurred over palms and soles. Courtesy of Rob Green, MD.
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). The CT scanning helped evaluate the extent of infection and exclude other pathologies, such as psoas abscess, osteomyelitis, and inguinal hernia.
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). The CT scanning helped evaluate the extent of infection and exclude other pathologies, such as psoas abscess, osteomyelitis, and inguinal hernia.
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). The CT scanning helped evaluate the extent of infection and exclude other pathologies, such as psoas abscess, osteomyelitis, and inguinal hernia.
Necrotizing cellulitis of toxic shock syndrome.
Soft tissue infection secondary to group A streptococci, leading to toxic shock syndrome.
Extensive debridement of necrotizing fasciitis of the hand.
The hand is healing following aggressive surgical debridement of necrotizing fasciitis of the hand (see Image 15).
Necrosis of the little toe of the right foot and cellulitis of the foot secondary to group A streptococci.
 
 
 
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