Infectious Diseases in Critical Care Medicine

staphylococcal enterotoxins are the paradigm of a large family of pyrogenic exotoxins called

superantigens (SAgs). For nonmenstrual TSS, the offending pathogen can virtually colonize

any site in the body (101–104). Recurrent menstrual TSS is a well-described phenomenon

(105,106). Two conditions are required for recurrence of TSS: persistent colonization with a

toxigenic strain ofS. aureusand persistent absence of neutralizing antibody. Recurrent TSS

develops exclusively among patients who fail to develop a humoral immune response to

the implicated staphylococcal toxin (107). Diagnosis of TSS is based on a constellation of

clinical and laboratory signs as proposed by the Centers for Disease Control and Prevention

(Table 5) (99).

In the late 1980s, a disease similar in appearance to TSS, yet caused by invasive

streptococci, was recognized and referred to as “toxic strep,” “streptococcal TSLS,” or “STSS”.

This condition was found to share many clinical features with TSS. M types 1, 3, 12, and 28

have been the most common isolates from patients with shock and multiorgan failure

(108,109). In the majority of cases toxin-producing group A streptococci have been isolated,

with streptococcal pyrogenic exotoxin A (Spe-A) production being most closely linked with

invasive disease. However, group A streptococci producing streptococcal pyrogenic exotoxin B

(Spe-B), streptococcal pyrogenic exotoxin C (Spe-C), streptococcal SAg, and mitogenic factor,

as well as non-group A streptococci have been found to be causative in individual cases of

STSS as well. Similar to classic TSS, the clinical signs of STSS are postulated to be mediated by

massive cytokine release (primarily TNF-a, IL-1b, and IL-6) as a result of toxin/superantigen

activity; in addition, streptolysin O, produced by 100% of streptococcal strains associated with

STSS, has also been shown to cause TNF-aand IL-1bproduction and has been demonstrated

to act synergistically with Spe-A (110–115). Very young, elderly, diabetic, or immunocompro-

mised persons are more susceptible to the acquisition of invasive streptococcal infection such

as STSS. However, the majority of cases of STSS have occurred in young, otherwise healthy

persons between 20 and 50 years of age. An absence of protective immunity is postulated as

Table 5 Toxic Shock Syndrome: Clinical Case Definition (CDC)

An illness with the following clinical manifestations:
Fever: Temperature102.0 8 F(38.9 8 C)
Rash: Diffuse macular erythroderma
Desquamation: 1–2 wk after onset of illness, particularly on the palms and soles
Hypotension: Systolic blood pressure90 mmHg for adults or less than fifth percentile by age for children aged
<16 yr; orthostatic drop in diastolic blood pressure15 mmHg from lying to sitting, orthostatic syncope, or
orthostatic dizziness
Multisystem involvement(three or more of the following):
Gastrointestinal: Vomiting or diarrhea at onset of illness
Muscular: Severe myalgia or creatine phosphokinase level at least twice the upper limit of normal
Mucous membrane: Vaginal, oropharyngeal, or conjunctival hyperemia
Renal: Blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or urinary
sediment with pyuria (5 leukocytes per high-power field) in the absence of urinary tract infection
Hepatic: Total bilirubin, alanine aminotransferase enzyme, or aspartate aminotransferase enzyme levels at
least twice the upper limit of normal for laboratory
Hematological: Platelets<100,000/mm^3
Central nervous system: Disorientation or alterations in consciousness without focal neurological signs when
fever and hypotension are absent

Laboratory criteria
Negative results on the following tests, if obtained:
Blood, throat, or cerebrospinal fluid cultures (blood culture may be positive forStaphylococcus aureus). Rise in
titer to Rocky Mountain spotted fever, leptospirosis, or measles

Case classification
Probable: A case that meets the laboratory criteria and in which four of the five clinical findings described above
are present
Confirmed: A case that meets the laboratory criteria and in which all five of the clinical findings described above
are present, including desquamation, unless the patient dies before desquamation occurs

Source: Adapted from Ref. 99.

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