Streptococcal toxic shock and other toxic shock syndromes

Toxic shock syndrome is found in the list of "Rarer infections with specific ICU considerations", a Level 1 from Section 2.1.5 in the second edition of the CICM Syllabus for the Second Part Examination. It has appeared in several past SAQs, most notably Question 27 from the first paper of 2024 which asked about Group A Strep, and  Question 1 from the second paper of 2007 which asked specifically about the features of staphylococcal toxic shock syndrome. Both streptococci and staphylococci produce superantigens, and because of this what follows below expends little effort to help discriminate between them. 

The information for this summary has been scraped together among the following sources:

• This NEJM case report (2013)
• A review article from PLOS (2011)
• Donald Low' overview from Critical Care Clinics (2013)

Epidemiology of toxic shock

Toxic shock syndrome is exceedingly uncommon in Australia, with one paper by Chen et al (2016) finding only 62  paediatric cases from eleven years in Victoria. Invasive Group A strep infections are "notifiable" here, meaning that the cases are now recorded centrally, allowing the generation of reports such as this one. That specific health district had a peak incidence of 9 cases per 100,000 of population, with an increasing trend. Mortality was 12.6% for all cases (whereas in Europe the mortality from this is 30%), with a median age of 36, which makes sense considering the pathophysiology. Wright et al (2021) also noted an increased incidence among Indigenous Australians.

Pathogenesis of toxic shock syndrome

Some staphylococci and some Group A streptococci produce a characteristic protein (the Toxic Shock Syndrome Toxin, or TSST-1, 2 and 3).

• TSST activates T-cells directly, acting as a "superantigen"
• Massive inflammatory cytokine release is the result
• Endothelial dysfunction and vasodilatory shock ensues, which is out of proportion to the severity of the initiating infection.
• As these are classically healthy young people who have never seen a single strep infection, they do not have the antibodies to neutralise the shock protein. This is the rationale for the IVIg.

In Low's article, staphylococcal TSS is separated into "menstrual" and "non-menstrual" categories. Apparently, the tampon introduces oxygen, which is required for TSS-1 production.

In contrast, streptococcal toxic shock was typically associated with:

• necrotising fasciitis
• severe puerperal sepsis
• necrotising pneumonia
• suppurative pharyngitis
• septic arthritis
• meningitis

Clinical manifestations of toxic shock syndrome

According to the CDC, there are four stereotypical criteria for toxic shock syndrome, all of which must be met:

• High fever (> 38.9°)
• Hypotension and shock
• Rash consistent with diffuse macular erythroderma
• Desquamation, particularly of the palms and soles

There are also non-diagnostic associated features:

• Rapid onset: ~ 2 days
  • One might expect
• Multisystem organ involvement
• Staphylococcus may grow in the blood (but blood cultures otherwise negative)
  • Staphylococcus aureus is only rarely (5%) recovered from blood cultures in toxic shock, in contrast to Group A Streptococci which are typically easily cultured from the blood.

Management

• Source control
  • Especially in necrotising fasciitis, essential for survival
  • Debride dead tissue and remove sanitary products responsible
• Antibiotics
  • β-lactam antibiotics:
    • Benzylpenicillin is usually enough
    • or cephazolin/vancomycin where allergic
  • Clindamycin as an adjunct
• Prevention of toxin production
  • Clindamycin (say 600mg tds or 900mg tds IV) is indicated to disrupt bacterial synthesis of the toxic shock protein
• Removal of circulating toxin
  • Intravenous immunoglobulin (to bind circulating TSST)
  • 2g/kg as a single dose
  • IVIG also decreases in the production of proinflammatory cytokines and causes a downregulation of adhesion molecules and chemokines.
• Unproven treatments
  • Corticosteroids are known from case series (Vergis & Gorard, 2007) but are not a part of the established approach

The Oh's Manual chapter on severe soft tissue infections (Ch. 71, p. 736) brings up some interesting points about the use of IV immunoglobulin in toxic shock:

• All the evidence in support of this therapy comes from the same group of researchers
• The mortality benefit was a trend, and was non-significant
• The dose of IVIG varies;
  • Some give a single dose of 2g/kg
  • Others give 1g/kg and then 0.5g/kg for two more days
• The effect of the polyspecific IVIG might vary from bottle to bottle, as the immunoglobulin infusion is a pooled product, representing a mixture of immunoglobulins from the population. Populations might vary in their expression of anti-TSST antibodies. One might call this the "Soylent Green Effect" (flavour varies from person to person).