Common causes of toxic shock syndrome
S. aureus or strep pyogenes produce super antigens that result in overactivation of T-cells and cytokine storm. Cytokine storm results in capillary leak, tissue damage, multigrain failure and death.
Common situations that may promote staph toxic shock syndrome
Superabsorbant tampons, abscesses, wounds and post-inflluenza. Sometimes the source of infection is not as clinically apparent as strep TSS.
CDC definition of staph TSS
1) Fever > 102 2) Hypotension (SBP < 90) 3) Diffuse macular erythroderma 4) Desquamation of skin 1-2 weeks later 5) 3+ organ system involvement. +/- s. aureus. - serology for measles, leptospirosis, Rocky Mountain Spotted Fever
Common situations that may promote strep toxic shock syndrome
Invasive skin infections (necrotizing fasciitis, myositis) and bacteremia.
How would you know this is necrotizing fasciitis?
Tenderness extends beyond the redness because the infection moves along fascial planes faster than it does through the skin.
Diagnosis of strep TSS
1) Isolate strep pyogenes 2) Hypotension (SBP < 90) 3) 2+ of the following: renal insufficiency, coagulopathy, increases liver enzymes, RDS, erythematous macular rash and soft tissue necrosis.
Staph superantigens? Strep superantigens? How do they work?
Staph: TSST-1 (menstrual), enterotoxins A-E. Strep: Strep pyrogenic exotoxins and strep superantigen. These antigens bind to the beta-subunit of the T-cell receptor and MHC II. This activates up to 20% of all CD4+ T-cells that go on to produce IFN-gamma, IL-1, IL-2, IL-6, IL-8, TNF-alpha & beta. These promote acute phase reactant production in the liver, ROS release from PMNs and leaky capillaries that ultimately causes inflammation, tissue injury and shock.
Tx for TSS
1) IV fluids 2) Find site of infection 3) Antibiotics: vancomycin (MRSA), nafcillin (MSSA), penicillin (group A strep) + clindamycin (blocks toxin production) 4) +/- IVIG
What is endotoxin synonymous with?
LPS, the principle component of the outer membrane in gram negative bacteria.
How does our body recognize LPS?
TLR4. Binding of LPS to TLR4 results in macrophage activation and TNF-alpha release, which is the key mediator in endotoxic shock. After TNF, IL-1 is released, then IL-6.
Common pathogens that are recognized by pattern recognition receptors (PRRs)?
Pathogen associated molecular patterns (PAMPS). PRRs include TLRs.
Treatment of shock due to gram - endotoxic shock
1) IV fluids 2) Broad spectrum abx 3) Vasopressors/inotropes if needed. Note than many of the cytokine inhibitors have not been shown to be effective.
Why is meningococcus so scary
“No other infection so quickly slays”. There are high levels of endotoxin released by the organism because the bacteria blebs lots of it into the blood that cause cytokines TNF, IL-1, IL- and IL-8 to go through the roof.
Infection caused by gram-negative, encapsulated, aerobic diplococci shown in the CSF of a patient that died from meningitis below. What are the pathogenic serotypes?
Neisseria meningitides: A, B, C, X, Y, W135. Note that these have the ability to undergo capsule switching, which helps protect them from macrophages and complement-mediated lysis.
Highest rate of meningococcus infection
< 1 years old. There is a little bump around age 18.
Classic symptoms of meningococcal infection
Hemorrhagic petechial rash (in areas of pressure, especially belts and elastic straps), meningismus (neck stiffness/photophobia) and impaired consciousness. Note that by the time these symptoms present it is usually too late.
How does meningococcal infection present, what is the spectrum?
Meningitis, meningitis + meningococcemia, meningococcemia w/o meningitis.
Common sequelae in patients affected by meningococcemia
Loss of limbs, organ destruction, loss of hearing.
How does meningococcus affect the blood vessels and cause petechia?
Vessels are infected and causes vasculitis.
Synonyms for meningococcemia
Waterhouse-Friedrichsen syndrome and purpura fulminans, note that both of these are associated with necrosis of the adrenal glands.
Why doesn’t everyone get meningococcemia? What factors increase risk for infection?
Many people have it in their throat, but not all strains are infectious. Also people with terminal complement deficiency (C5-C9), variations in mannose-binding lectin pathway, asplenia, cigarrette smoking and preceding URI increase risk.
Dx of meningococcemia
CSF culture or PCR
Tx of meningococcemia
3rd generation cephalosporin (ceftriaxone). Prophylaxis with quinolone or rifampin for close contacts. You could also give tetravalent (A,C,Y,W135) vaccine for MCV.
Common cause of meningococcemia not covered in vaccine