1. Bacterial Skin Infections
Paul A. Gulig, Ph.D.

2. Skin infection case
A 45 year old pastry chef, cut his left forearm with a knife during the course of his work. Over the next week, he noticed swelling, redness and warmth at the site. After 4 more days, he developed fever with shaking chill and came to the emergency room with severe low back pain. On physical exam, he had a fever of 39.4oC, his left forearm was swollen with an area of central softness, indicating an abscess. He had tenderness to pressure over his lower spine.
The laboratory reported that he had a high white cell count. A Gram stain of pus aspirated from the forearm showed Gram positive cocci in clusters.

3. Questions What are the most common bacteria causing skin infections?
Mechanisms of tissue damage?
How can a forearm infection result in back pain?
What are the predisposing conditions?
Prevention and treatments

4. SKIN Epidermis Basement membrane Dermis Subcutaneous fat
Stratum corneum -major physical barrier
Langerhans cells - phagocytic defenses
hair follicles, sweat glands, sebaceous glands - weak points for entry
Basement membrane
Dermis
collagen, elastin
blood vessels, lymphatics
Subcutaneous fat
Superficial fascia
Muscle

5. SKIN AND WOUND INFECTIONS
Encounter
Typical normal flora to 104 CFU/cm2
Density affected by:
environmental climate
microclimate (anatomy) - armpit/groin vs. elbow
Dryness and exfoliation barriers
pH 5.5 from sebum lipids by bacteria (body odor!)
Lower temperature (33C)
NaCl from sweat - Staphylococcus epidermidis
Dry areas - gram-positive cocci, diphtheroids
Sebaceous areas - Propionibacter acnes
Wet areas - gram-negative rods
Bed-ridden patients - enterics

6. SKIN AND WOUND INFECTIONS
Entry
From outside - wounds, burns, surgery, injections, catheters, bites, disease, blood supply disruption
E.g., Staphylococcus aureus
no wound CFU/cm2 required
with wound - 10 CFU/cm2 required
From within - blood and lymph
Adherence mechanisms

7. SKIN INFECTIONS Impetigo - epidermis Folliculitis - hair follicles
Abscesses:
Folliculitis
Furuncles (Boil)
Carbuncles – coalesced furuncles
Erysipelas - dermal lymphatics
Cellulitis - subcutaneous fat layer
Fasciitis
Gangrene (myonecrosis)
Systemic effects: Toxic shock, sepsis

8. Impetigo S. aureus and S. pyogenes
Don't forget Post-Streptococcal Glumerulonephritis

9. Folliculitis
Microabscess
S. aureus

10. Furuncle (boil) Carbuncle
Extension of folliculitis
Carbuncle
Coalesced furuncles

11. Erysipelas Superficial lymphatic involvement
Raised, bright-red plaques with sharply defined borders
Usually group A streptococci
Deep lymphatics = lymphangitis (tracking)

12. Cellulitis Subcutaneous tissue Acute inflammation
Redness, induration, heat, tenderness
Indistinct borders
Lymphangitis possible
S. aureus and S. pyogenes
From cat/dog bites - Pasteurella multocida

13. Staphylococcus aureus
Local skin infections
Impetigo, Folliculitis, Furuncles (boil), Carbuncles
Local infection - systemic symptoms
Staphylococcal Scalded Skin Syndrome (SSSS)
Toxic shock syndrome (TSST-1)
Systemic infections
Sepsis
Endocarditis
Osteomyelitis

14. Pathogenesis Encounter Entry Spread
Humans only? (apparently some pets can be colonized)
Broken skin or mucous membrane (nose)
Entry
Adhesins: Collagen-, fibrinogen-, and fibronectin- binding proteins
Spread
Generally not as invasive as Streps
Can spread hematogenously – abscesses, osteomyelitis, septic arthritis
Enzymes
Hyaluronidase, collagenase
Lipase, nuclease, protease
Coagulase

15. Pathogenesis Multiplication grows well anywhere Evade Defenses
catalase, leukotoxins, Fc binding protein
Predisposing conditions:
Complement disorders
Neutropenia: chemotherapy
Chronic granulomatous disease (CGD)
reduced production of H2O2 and O2-.
“Lazy leukocyte” (chemotaxis deficiency)

16. Pathogenesis Damage Outcome Inflammation, toxins, degradative enzymes
Superantigen (TSST-1)
Dermonecrotic toxin
Enterotoxins
Outcome
Self-limiting to fatal
Transmission
Fomites
Person-person contact

17. Staphylococcal scalded skin syndrome (SSSS)
Dermonecrotic toxin (exfoliative toxin)
Bullous exfoliative dermatitis

18. Toxic Shock Syndrome Toxic shock syndrome toxin (TSST-1) Superantigen
Produced by 5-25% isolates
Tampon or infected wound
Fever
Rash
Exfoliation of skin
Shock (death rate 3%)

19. TSST-1 Mechanism of action Treatments Immunosuppressants
Interacts with MHC-II and Vβ T-cell receptors
Stimulate the release of cytokines (IL-1, IL-2, and TNFα)
Treatments
Immunosuppressants
Prevent T-cell activation and cytokine releases
Corticosteroids
Reduce inflammatory effects

20. Streptococcus pyogenes
Skin infections
Impetigo
Erysipelas
Cellulitis
Necrotizing fasciitis (flesh-eating bacterium)
Systemic effect
Streptococcal Toxic Shock-like Syndrome (STSS)
Spe (similar to TSS by S. aureus)
Scarlet fever (pyrogenic toxin – lysogenic conversion)
Post-infection nonsuppurative sequellae
Rheumatic fever (associated with pharyngitis)
Glomerulonephritis (pharyngitis and skin)
Review pathogenesis

21. S. pyogenes
Necrotizing
fasciitis
Scarlet Fever

22. Clostridial infections
Obligate anaerobes
Gram-positive rods
Spore-forming
Soil contamination

23. Clostridium botulinum
Remember food intoxication, infant botulism
Wound botulism
Deep wounds
Anaerobic environment
Botulinum toxin (BT) leaks into blood
BT enters neurons
Inhibits acetylcholine release in neuromuscular junction
prevent muscle contraction = flaccid paralysis
Therapy
Antibiotics
Antitoxin
Supportive therapy

24. Clostridium tetani Tetanus Local infection with systemic effect
Early symptoms
Locked jaw
Stiffness in the neck and abdomen
Difficulty swallowing
Late symptoms
Fever
Elevated blood pressure
Severe muscle spasm

25. Tetanus Tetanospasmin (AB toxin) Released when cell lyses A domain
zinc endopeptidase, cleaves synaptobrevin (vesicle-associated membrane protein VAMP)
stops the release of inhibitory neurotransmitters GABA and glycine
B domain
Binds neuron
Acts in spinal cord, prevents the inhibition of contraction of opposing sets of muscles – hence, tetanic or spastic paralysis.
Vaccine
Tetanus toxoid

26. Clostridium perfringens
Gas gangrene
Alpha toxin (phospholipase C)
Zinc metallophospholipase
hemolysis and bleeding
Gas formation
Mechanism
PLC cleaves the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).
Ischemia
Myonecrosis, shock, renal failure and death

27. Alpha toxin Structure Mechanism of action Treatment Single peptide
C-terminal domain binds phospholipid bilayer
N-terminal domain has phospholipase activity
Treatment
Debridement and excision
Antibiotics
Hyperbaric oxygen therapy

28. Other Skin and Mucus Membrane Infections
Staphylococcus epidermidis
Catheters and prostheses
Vibrio vulnificus
From shellfish and salt water
Flesh-eating – necrotizing fasciitis
Obligate anaerobes (usually polymicrobic and foul smelling)
Puncture wounds
Deep wounds
Impaired blood supply
Gram negative bacteria
Decubitus ulcer (bed sores)
Fecal contamination
Pseudomonas aeruginosa
Burns
Surgical wounds

29. Other Skin and Secondary Infections
Osteomyelitis
Muscle infections
Don't forget cutaneous anthrax
Purpura from N. meningitidis
Rashes from Lyme disease and RMSF
Rickettsia rickettsii can be transmitted to human hosts through the bite of an infected tick.
Viral exanthems
Other viral infections with skin manifestations
Coming soon to a class near you – fungal infections
Your patient does not walk into your office and say, "Doc, I have this bacterial skin infection..."

30. Case (cont’)
Staphylococcus aureus was cultured from the pus. Blood cultures were positive for the same organism. X-ray of the lumbar spin showed erosion of the third lumbar vertebra - osteomyelitis. The organism was resistant to penicillin but sensitive to oxacillin, which was used to treat the chef with a good result.