L20. Osteomyelitis

Question 1

What is osteomyelitis, and what are the main pathogens for children vs older adults

Answer 1

Infection or inflammation of the bone marrow.

Staph Aureus = 80% of young cases. 
Strep Pyogenes = mainly adults
Coagulase - staph (commensal skin) = iv drug users
Group B strep= mainly infants
\+Hib, Enterobacter spp.

Question 2

What sites are more likely to be infected on children and how does osteomyelitis present

Answer 2

Mainly at the end of long bones: Femur, tibia, humerus although it relates to risk of infection. More common in boys > girls. Higher in developing countries

Presents as

• limping/inability to walk,
• fever, focal tenderness, redness, swelling around bone

Question 3

How is Osteomyelitis diagnosed

Answer 3

1. Symptoms with presentation
2. Blood test for increased WBC, CRP, bacteria if bacteremia
3. MRI to confirm diagnosis (expensive) or bone biopsy (highly invasive but specific). Xray and CT not sensitive to early disease

Question 4

What are the tests to differentiate between GAS and staph a (the pathogen involved in osteomyelitis)

Answer 4

1. Gram staining: stain is soaked up by bacteria and crystalises in the peptidoglycan wall. Then bacteria are visualised under microscope
   - GAS and S. aureus are both Gram positive cocci so stain doesn’t wash away.
   - GAS has chains, whereas S aureus are in grapelike clusters.
2. Catalase test using H2O2 on samples
   - streptococcus are negative, Staph is positive

3a - Strep bacteria are separated using haemolysis on blood agar plate. (Viridans is a, GAS is b, Enterococcus is g)

3b) Staph bacteria are separated using coagulase test: adding bacteria to plasma. Positive causes fibrin clot = S. aureus. Negative is skin dwelling staphyloccocus eg. S epidermitis.

Question 5

Where does S aureus colonise, % of carriers, mode of transmission and what are the common infections it causes

Answer 5

Colonises anterior nares, 20% assymptomatic carriers. It has human-human transmission and can survive long on the hands.

Diseases: impetigo, folliculitis, staph scalded skin syndrome, cellulitis, septic arthritis, acute infective endocarditis, pneumonia, necrotising fascitis, toxic shock syndrome

Question 6

What are the colonisation and immune evasion factors that help Staph Aureus a strong pathogen (1,5)

Answer 6

1. Adhesins - eg. MSCRAMMs to bind to host tissues and start colonisation
2. Immune evasion factors:
   a) Cytolysins: kill RBC, leukocytes, tissue cells

b) Capsule outside of cell wall which prevent opsonisation with C3b/IgG and phagocytosis
c) Biofilm: extracellular polysacharide which help bacteria group and stick to foreign surfaces. Prevents antibiotics/immune components from penetrating
d) Protein A binds IgG via Fc region which prevents opsonisation and phagocytosis.
e) Cell bound coagulase which binds prothrombin to induce fibrin polymerisation on the cell surface to prevent opsonisation

Question 7

What is produced by S. aureus and S pyogenes that contributes toxic shock - what is toxic shock

Answer 7

Superantigens : family of heat resistant proteins which are highly potent T cell mitogens, trigger strong pro-inflammatory immune response, synergestic effect with endotoxin (LPS) which causes septic shock:

systemic inflammation with tissue destruction, vascular leakage, multiorgan failure and

Question 8

How is S. aureus infection treated and what treatments don’t work and why

Answer 8

Prolonged antibiotic treatment (wks-> mo)

1. 90% are resistant to B-lactam antibiotics which irreversibly bind transpeptidase. eg. Penicillin, cephalosporin, carbapenemase.

• These can be treated using Methicililn eg. Flucloxacillin. which cannot be destroyed by B-lactamases.
• Or Penicillin combined with B-lactamase inhibitor: eg. Amoxicillin + clavulanic acid = augmentin

2. 30% are resistant to Methicillin (MRSA) because they have a new penicillin binding protein which low affinity for B-lactams.

• This can only be treated with Vancomycin.
  VRSA are rare but increasing for which there is no treatment.

Question 9

What are the spreading factors that allow staph aureus to spread into deeper tissue/ blood. (4)

Answer 9

a) Staphylokinase (dissolve fibrin clots)
b) Lipases
c) DNAses (dissolve dead leukocyte DNA which makes pus viscous
d) cytolysins. (dissolve epithelial cells)

Question 10

Describe the pathogenesis of Osteomyelitis, including 3 routes for colonisation to take place (4)

Answer 10

Progresses from
1. bacterial colonisation/proliferation of bone:

a. Trauma (joint replacement, bone surgery, root canal)
b. Spreading from local area of infection (eg. SSTI, diabetic ulcer, septic arthritis)
c. Haematogenous route (bacteremia, chicken pox (scratching sores))

2. Neutrophil infiltration to infected site to fight bacteria = inflammation/formation of pus
3. Abscess formation leading to devascularisation and necrosis of bone
4. Potential to spread to joint (septic arthritis) or become chronic through evasion of immune system/drugs inside osteoblasts