507 Bacterial pathogenesis Toxic shock syndrome 507 Bacterial pathogenesis

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

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

Mode of action of superantigens

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

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

Pathophysiology Absence of antibodies against superantigens is a major risk factor to developing TSS > 85% of women aged 13-40 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

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 10-21 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.

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

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

Progress of clinical features

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

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

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)