1. 507 Bacterial pathogenesis
Toxic shock syndrome
507 Bacterial pathogenesis

3. Toxic Shock Syndrome
Toxin mediated, acute systemic disease resulting in shock and multi-system organ failure
Staphylococcus aureus and Group A Streptococcus pyogenes are the most common organisms

4. Pathophysiology Bacterial endotoxins act as superantigens
Protein toxins that have the ability to trigger excessive T-cell activation with downstream activation of other cell types and cytokine release
Conventional antigen presentation activates 0.01% of host T-cells compared to superantigen binding which activates up to 20-30% of host T-cells

5. Mode of action of superantigens

6. Pathophysiology
Also associated with rapid increase in cytokine production from T-cells
T-cell activation leads to additional recruitment of T and B cells to the site of infection

7. Pathophysiology
Staphylococcal TSS-T1 (Toxic shock syndrome Toxin 1) is responsible for 95% of menstrual related TSS.
TSS-T1 able to cross mucosal barriers
Also detectable in 50% of non menstrual TSS
Not all patients colonized with Staph aureus or strep pyogenes develop TSS and interaction between host immune system and pathogen play an important role

8. Pathophysiology
Absence of antibodies against superantigens is a major risk factor to developing TSS
> 85% of women aged have TSS-T1 antibodies that are thought to be protective
Low or negative antibody titers are found in 90.5% of patients with menstrual TSS
More than 50% of these patients fail to seroconvert within 2 months of their illness
Seroconversion: is the development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization

9. Clinical Manifestation
Hallmark symptoms include fever, shock and multi-system failure
Staphylococcal TSS: starts with flu like prodromal illness including fever, GI distress and severe myalgia. Desquamation is a late feature and happens days after initial onset of symptoms.
Blood cultures are positive in < 5% of Staph TSS
Menstrual and non menstrual TSS are identical clinically
Up to 95% of patients diagnosed with menstrual TSS have onset of illness during menses
Fever and rash more prevalent in early disease
Recurrence of menstrual TSS well documented but rare in non menstrual TSS
Desquamation: the shedding of epithelial elements chiefly of the skin, in scales or sheets.

10. Derm manifestations
Diffuse macular (spotty) erythroderma followed by desquamation in 1-2 weeks
Conjunctival injection
Macular: spot

11. Clinical manifestation
Mucosal (oral and genital) hyperemia (increase in blood flow)
Strawberry tongue

12. Progress of clinical features

13. Treatment Aim to decrease bacterial load and endotoxin production
Penicillinase resistant penicillin, cephalosporin for suspected Staphylococcus aureus TSS
Vancomycin for suspected MRSA
1st antibiotic to decrease bacterial load and clindmycin inhibits synthesis of bacterial endotoxin

14. Treatment
Group A Streptococcus very sensitive to B-lactam agents including Penicillin G (first line treatment)
Although Penicillin is bactericidal, it is less effective against high organism load (ineffective if treatment delayed by > 2 hours)
Given with Clindamycin which is inhibitory of protein synthesis of superantigen production
Inhibitor of endotoxin production in both Staph and Group A Strep

16. Treatment
Possible consideration of starting IV immunoglobulins if no clinical response within the first 6 hours of IV antibiotics
IV immunoglobulin G (IVIG) may reduce mortality.
High dose corticosteroid may also improve outcome as shown in isolated case reports
21 patients with streptococcal toxic shock syndrome randomized to high-dose IVIG vs. albumin placebo for 3 days, all patients given antibiotics and standard care, study terminated early due to low recruitment, 28-day mortality was 10% with IVIG vs. 36% with placebo (NNT 4) or 12.5% vs. 30% in subgroup with documented invasive group A streptococcal infections (NNT 6) but results were not statistically significant; no differences in prevalence of chronic organ failure or times to resolution of shock and to control of tissue infection; no apparent side effects (Clin Infect Dis 2003 Aug 1;37(3):333 in J Watch Online 2003 Sep 9)
(J Med Case Reports 2007 Feb 16;1:5)