Skin and soft tissue infection SR

Question 1

Sequence of infection

Answer 1

1. colonise the skin
2. cytolysins/toxins released to damage epithelial cells
3. damaged cells release cytokines eg IL1 TNFalpha IL8 –> chemotaxis
4. macrophages and dendritic cells follow chem gradient
5. PAMPs eg peptidoglycan or lipotechoic acid bind to PRR (pattern recognition receptors) –>innate immunity
6. capillary endothelial cells express cellular adhesion molecules such as selectins
7. selectins interactwith carbohydrates on neutrophil causing them to slow and roll and tether to endothelium
8. tethered neutrophils are pulled between the endothelium via PECAM (Platelet endothelial cell adhesion molecule) interactions (diapedesis)

Question 2

3 triggers of complement system

Answer 2

1. bacterial carbohydrates bind to proteins (mannose binding lectin)
2. complement spontaneously starts to form on cell surfaces
3. antibody (Ig) binds to bacterial antigen

Question 3

Complement pathway

Answer 3

1. a number of proteins combine to form C3 convertase which cleaves C3 into C3a and C3b.
2. C3b is an opsonin –> binds to bacteria and enhances recognition and phagocytosis
3. some C3b binds back to C3 convertase to form C5 convertase which cleaves C5 to C5a and C5b.
4. C5a –> chemotactic proteins
5. C3a and C5a –> anaphylatoxins –> vascular permiability
6. C5b binds with C6 to C9 to form the membrane attack complex (MAC) which lyses bacteria (gram negative)

Question 4

Causes of pain

Answer 4

cytokines
cellular debris
bacterial degradation products

Question 5

Main cause of skin and soft tissue infection

Answer 5

1. streptococcus pyogenes (gram +ve)
2. staphylococcus aureus (gram +ve)
3. Fungi - dermatophyte moulds and tinea
4. viruses

Question 6

Streptococcus pyogenes

Answer 6

1. gram +ve cocci
2. rheumatic fever
3. bone, joint, skin, soft tissue, pharynx infections

Question 7

Streptococcus pyogenes’ immune invasion

Answer 7

1. Streptolysins damage cells such as neutrophils and platelets
2. DNAses digest DNA to avoid being trapped in neutrophil extracellular traps
3. streptokinase activates plasminogen into plasmin which digests fibrin
4. adhesions bind to host tissue (MSCRAMMs = microbial surface components recognizing adhesive matrix molecules)
5. HA capsule prevents opsonization and phagocytosis
6. M proteins (another MSCRAMM) bind factor H, which degrades complement. M proteins also interfere with C3b binding to C3b receptor on phagocyte cell
7. C5a peptidase degrades C5a reducing chemotaxis

Question 8

Diagnosis of skin infection

Answer 8

Clinical
(blood test for antibodies and cytokine measures are not useful)
Purulent material can be tested in lab
Swabs of intact skin are not useful
If requiring admission to hospital, blood cultures should also be taken –> check for sepsis

Question 9

Skin infection treatment

Answer 9

1. Supportive care to maintain “normal” physiology
2. Rest and elevation
3. Analgesia (reduce pain)
4. Antimicrobial drugs (s.pyogenes and staph aureus)

Question 10

Penicillin function

Answer 10

1. binds to transpeptidase which forms bonds between tetrapeptide chains and prevents cross-linking
2. inhibition of transpeptidase impairs repair of cell wall and leads to release of autolysins that digests the cell wall
3. death of bacteria

• *all s.pyogenes are susceptible
• *10% of staph aureus only

Question 11

B-lactam antibiotics

Answer 11

1. penicillin derivatives
2. cephalosporins
3. carbapenems
4. monobactam