Toxic Shock, Endotoxemia, and Meningococcus Flashcards
What causes Toxic Shock Syndrome?
Superantigen activates T-cells, bypassing the usual steps in an antigen-mediated response, leading to a…
CYTOKINE STORM
Where does a superantigen bind?
Directly to the MHC II molecule and Vβ subunit of the TCR
Bypasses the MHC peptide binding groove
How many CD4+ T cells are activated by a superantigen (compared to a normal response)?
Normally, a peptide presented by an APC will activate < 1% of all CD4+ T cells
Superantigens activate 20% of all CD4+ T cells
What are the superantigens for S. aureus and S. Pyogenes?
S. aureus = TSST-1 (fever, shock, capillary leakage)
S. pyogenes = Exotoxin A (shock, capillary leakage, cardiotoxicity)
CDC definition for Staph Dx
Fever > 102
Hypotension (SBP <90)
Diffuse rash
Desquamation at 1-2 wks
3 or more organ systems involved
CDC definition for Strep Dx
Isolation of S. pyogenes from normally sterile site
Hypotension
≥ 2 of: renal insufficiency, coagulopathy, increased liver enzymes, ARDS, erthematous macular rash, soft tissue necrosis
SIRS Criteria
(Systemic Inflammatory Response Syndrome)
≥2 of:
T > 38 or < 36 (100.4 and 96.8)
HR > 90
RR > 20, PaCO2 < 32
WBC > 12,000 or < 4,000 (or > 10% bands)
Sepsis Criteria
SIRS
+
Source of infection
Severe Sepsis Criteria
Sepsis (SIRS + source)
+
Lactic acidosis, SBP <90 or a drop ≥ 40
Septic Shock Criteria
Severe Sepsis
+
Hypotension despite fluid resuscitation
Common causes of Staph (toxin-mediated)
Tampon
Nasal packing
Recent surgery
Wound
Post-partum
What is the most likely cause of someone presenting w/ a skin infection that causes severe pain and bacteremia?
Strep
What is the mortality rate of strep compared to staph?
Strep has a greater mortality rate (5-10%) than staph (3-5%)
How do you distinguish staph from strep for toxin-mediated infections?
Remember, strep looks worse and is painful
Staph: think diffuse rash
(less likely to involve skin/soft tissue infection, severe pain at site of infection, or bacteremia)
Endotoxin
Poisonous substance from within a pathogenic organism
Synonymous with LPS (only Gram - bacteria)
What are the 3 components of LPS?
- Lipid A portion (outermost) = toxic component that overactivates the immune system (similar to cytokine storm seen with superantigens)
- Core component
- O polysaccharide (innermost) = sugar used to distinguish b/w differenty types (i.e., E. Coli O157)
TLR4
A PRR (pattern recognition receptor) that recognizes LPS immediately
PAMP
Pathogen Associated Molecular Protein
Ex: LPS
Where are PRRs expressed
Transmembrane proteins expressed by cells of the innate immune system and epithelial cells
How many PRRs/TLRs are found in humans?
10
(13 in mice)
Mechanism of LPS
Ligates TLR4, leading to:
activation of macrophages
the production of inflammatory cytokines (C5a, TNF-α, IL-1, and IL-6)
upregulation of co-stimulatory and adhesion molecules (coagulation)
= FEVER, HTN, and TISSUE DAMAGE
Why do we have TLR4?
Without it, we would be markedly susceptible to
gram (-) infections
What does an increased level of IL-6 correlate with?
Increased mortality
Unlike TNF-α and IL-1, IL-6 does not produce shock symptoms
Tx of Septic Shock d/t gram (-) bacteria
IV fluids
Eradication of infection (broad sprectrum abx and consider surgery)
Vasopressor and Inotropes if needed
“No other infection so quickly slays”
Gram (-), aerobic, diplococci
Metabolizes maltose and glucose
Grows on Thayer-Martin media
N. meningitidis
How is neisseria meningitidis serotyped?
By capsule (13+ serogroups) = virulence factor
Capsule protects against dessication, phagocytosis, and complement-mediated lysis
Which serotypes of neisseria meningitidis are virulent?
A, B, C, X, Y, and W135
(B, C, and Y are common in the U.S.)
(Africa = A and W135)
Initial symptoms of neisseria meningitidis vs late symptoms
Initial symptoms are non-specific (fever, headache, and muscle pains)
Late symptoms are “classic”
- Hemorrhagic rash (petechiae under bra strap or belt line)
- Meningismus (stiff neck, photophobia)
- Impaired consciousness
Why does neisseria meningitidis progress so quickly?
D/t high levels of endotoxin:
leads to dramatic increase in TNF-α, IL-1, IL-6, and IL-8
Note: IL-8 is a chemokine that induces phagocytosis, histamine release, and respiratory burst
What is the reservoir for n. meningitidis?
Nasopharynx of humans
The invasive disease is uncommon b/c most meningococci are not very pathogenic
Waterhouse-Friderichsen Syndrome
When meningococcemia (w/ petechial rash) becomes fulminant…overwhelming infection
Shock, Purpura, and acute hemorrhagic necrosis of the adrenals
Worry about DIC, multiple organ failure, and death
Risk factors for contracting n. meningitidis
Terminal complement deficiency (C5-9)
Variants in mannose-binding lectin
Asplenia
Cigarette Smoking
Preceding URI
Gold Standard method of diagnosis for neisseria meningitidis
Cx blood or CSF
HOWEVER, when facing meningococcal sepsis, a gram stain of a punch bx of skin is more sensitive than a CSF stain
Which age group is most at risk for neisseria meningitidis?
The very young
(another peak during the 1st year of college, but not as many people comparatively)
Tx for n. meningitidis
Abx for 10-14 days (penicillin or 3rd generation cephalosporin)
Chemoprophylaxis for close contacts = rifampin, ceftriaxone, or cipro
Vaccine for n. meningitidis
MCV4 vaccine has antigens to serogroups A, C, Y, W-135 (not B)
New vaccines were approved that protect against serogroup B (which happens to be one of the most common in the U.S.)
Meningitis Belt
In sub-Saharan Africa (may result from dust interference with IgA secretion in nasopharynx)
Serogroup A
During the dry season (Dec-Jun)
Every 8-12 years (cyclic)
Ritter disease
aka Staphylcoccal Scalded Skin Syndrome
Occurs in children with S. aureus infection of the nasopharynx or skin. Bacteria produce exfoliative A and B toxins which cleave the protein desmoglein 1 (holds epidermal cells together). Results in a sunburn-like rash that spreads over the entire body
Subcutaneous manifestations of S. aureus infections
Staph leads to neutrophilic inflammation
- Furuncle (boil)
- Carbuncle
- Hidradenitis (infection of apocrine glands, most often in the axilla)
- Paronychia and felons (painful infection at nail beds or palmar fingertips, respectively)
How does Staph epidermidis differ from Staph aureus?
S. epidermidis (aka Coagulase negative Staph/CoNS)
Less virulent
Major cause of clinically significant infections in all age groups, largely due to its ability to grown on virtually all biomaterials composing indwelling medical devices (catheters and prosthetic cardiac valves)
Most common cause of nosocomial bacteremia
