Osteomyelitis

Question 1

What is osteomyelitis

Answer 1

infection localized to bone
inflammatory condition of bone/ bone marrrow caused by an infecting organism, most commonly Staphylococcus aureus.

Question 2

Epidemiology of osteomyelitis

Answer 2

UK incidence:
10 – 100 / 100,000 p/y.
Predominantly Children 80% of acute, haematogenous osteomyelitis
adolescents and adults get contiguous osteomyelitis (often associated with direct trauma)

Older patients: Diabetes mellitus/Peripheral Vascular disease/Arthroplasties
Men more than women

Question 3

Pathophysiology: 3 routes of transmission for osteomyelitis

Answer 3

• direct inoculation of infection into the bone:
  trauma or surgery,
  polymicrobial or monomicrobial.
• contact spread of infection to bone:
  from adjacent soft tissues and joints, polymicrobial or monomicrobial,
  older adults: DM, chronic ulcers, vascular disease, arthroplasties / prosthetic material,
• Haematogenous seeding:
  children (long bones)>adults (vertebrae)
  monomicrobial

Question 4

Pathogenesis of Osteomyelitis

Answer 4

• Behavioural factors:
  i.e. risk of trauma
• Vascular supply:
  Arterial disease
  Diabetes mellitus
  Sickle cell disease
• Pre-existing bone / joint problem:
  Inflammatory arthritis
  Prosthetic material inc arthroplasty
• Immune deficiency
  Immunosuppressive drugs
  Primary immunodeficiency

Question 5

Pathogenesis of haematogenous OM

Answer 5

Adults:
Usually >50 years
Vertebra > clavicle/pelvis»long bones
Children (85%)
Long bones»_space; vertebra

Question 6

What is the most common site of infection in long bone haematogenous OM?

Answer 6

Metaphysis

Question 7

Why is the metaphysis the most common site of infection?

Answer 7

• Main blood vessels penetrate the midshaft then go to either end to form vascular loops in the metaphysis.
• Here blood flow is slower and no endothelial basement membranes are so bacteria can enter the site from the blood
• capillaries also lack or have inactive phagocytic lining cells which allow growth of microorganisms.

Question 8

Where are children affected with haematogenous OM spread

Answer 8

• Children, with elongating long bones, the metaphysis is very metabolically active with a large flow of blood predisposing the vasculature to infection.
• With age, metaphysial blood flow slows.
• With age vertebrae more vascular so bacterial seeding of verebral endplate more likely

Question 9

How can lumbar vertebral veins lead to bacteria

Answer 9

lumbar vertebral veins communicate with those of the pelvis by valveless anastamoses.

Retrograde flow from urethral , bladder and prostatic infections may be a source of bacteria to these vertebrae

Question 10

Haematogenous OM in adults

Answer 10

Usually >50 years
Vertebra > clavicle/pelvis»long bones

Question 11

Haematogenous OM in children

Answer 11

Long bones»_space; vertebra

Question 12

People who inject drugs haematogenous OM

Answer 12

younger, more often clavicle and pelvis

Question 13

Who are the people with risk factors for bacteremia

Answer 13

central lines, on dialysis
sickle cell disease,
urinary tract infection, urethral catheterization
Similar factors as those for infective endocarditis

Question 14

S. aureus microbial factors

Answer 14

binds host proteins fibronectin, fibrinogen, and collagen
fibronectin binding proteins A and B (FnBPA / FnBPB)
Collagen-binding adhesin (CNA)
can survive intracellularly in cultured macrophages

Question 15

Which organisms cause OM

Answer 15

Staphylococcus aureus,
coagulase-negative staphylococci,
aerobic gram-negative bacilli (30%)
M. tuberculosis
Neisseria gonorrhoeae
Streptococci (skin, oral)
Enterococci (bladder, bowel)
Anaerobes (bowel)
Salmonella in sickle cell anaemia patients

Question 16

What is the histopathology of osteomyelitis

Answer 16

1.inflammatory exudate in the marrow
2. increased intramedullary pressure
3.extension of exudate into the bone cortex
4.rupture through the periosteum
5.Interruption of periosteal blood supply causing necrosis
6. Leaves pieces of separated dead bone
7. New bone forms here

Question 17

Acute changes of histopathology

Answer 17

• Inflammatory cells
• Oedema
• Vascular congestion
• Small vessel thrombosis

Question 18

Chronic changes of histopathology of OM

Answer 18

• neutrophil exudates
• lymphocytes & histiocytes
• Necrotic bone ‘sequestra’
• new bone formation ‘involucrum’

Question 19

What investigations can we do for OM

Answer 19

History
Examination
CRP - raised inflammatory marker
FBC- WCC - high in acute, normal in chronic
U and E
LFTs
HbA1C
MRI - Gold standard
CR
Plain Xray
Nuclear bone scan

Question 20

Symptoms (History)

Answer 20

Onset - several days.
dull pain at site of OM
may be aggravated by movement.
- Fever
- Pain
- Overlying redness
- Swelling
- Malaise

Question 21

Signs of clinical OM (Examination)

Answer 21

Systemic:
Fever, rigors, sweats, malaise

Local:
Acute OM-
tenderness, warmth, erythema, and swelling
Chronic OM-
tenderness, warmth, erythema, and swelling

PLUS any of
draining sinus tract
deep / large ulcers that fail to heal despite several weeks treatment*
non-healing fractures

Question 22

OM in hip vertebrae or pelvis

Answer 22

pain but few other signs or symptoms.

Question 23

OM Vertebral: lumbar > thoracic > cervical

Answer 23

Posterior extension - epidural and subdural abscesses or even meningitis.
Extension anteriorly or laterally can lead to paravertebral, retropharyngeal, mediastinal, subphrenic, retroperitoneal, or psoas abscesses.

Question 24

OM Joint - can also present as septic arthritis.

Answer 24

when infection breaks through cortex resulting in discharge of pus into the joint (knee, hip, and shoulder).
More common in infants due to patent transphyseal blood vessels and immature growth plate

Question 25

What is shown in a plain x-ray in chronic osteomyelitis

Answer 25

cortical erosion, periosteal reaction, mixed lucency, Sclerosis sequestra soft tissue swelling

Question 26

Why is an X ray not the best especially in early OM?

Answer 26

Poor sensitivity and specificity,

Question 27

Why is MRI good?

Answer 27

marrow oedema from 3-5 days Delineates cortical, bone marrow and soft tissue inflammation

Question 28

How can we make a definitive diagnosis?

Answer 28

Microbiology and histology: Bone biopsy Positive Blood cultures

Question 29

Bone biopsy for OM

Answer 29

obtained via sterile technique, Open bx >>> needle bx 2 specimens Culture 16sRNA PCR may be necessary Histology showing inflammation and osteonecrosis

Question 30

Positive blood cultures

Answer 30

may obviate the need for invasive diagnostic testing if the organism isolated from blood is a pathogen likely to cause osteomyelitis. +ve in 50% of Acute OM most useful if hematogenous OM

Question 31

Differential diagnosis for OM

Answer 31

Soft tissue infection (Cellulitis and erysipelas) Charcot joint Avascular necrosis of bone Causes: steroid, radiation, or bisphosphonate use. Gout uric acid crystals in joint fluid / more acute presentation Fracture Bursitis Malignancy

Question 32

Surgical treatment for OM

Answer 32

Debridement (remember Bromfield “we cannot be too early in letting it out”) Hardware placement or removal

Question 33

Antimicrobial therapy for treatment

Answer 33

Initial broad spectrum empirical therapy “start SMART” S. aureus or MRSA? gram-negative organisms? Special population: IVDU/HbSS? Tailored to culture and sensitivity findings “then FOCUS”. Bone penetration of drug Prolonged duration

Question 34

Antibiotics to use

Answer 34

Levofloxacin Ciprofloxacin Moxifloxacin Vancomyocin

Question 35

Treatment duration

Answer 35

Knowing when to stop treatment is very difficult 6 weeks of IV considered minimum switch to oral alternatives may work in some situations Stopping treatment guided by CRP response failure to respond requires re-imaging

Question 36

TB osteomyelitis

Answer 36

May be slower onset Systemic symptoms Epidemiology is different from pyogenic OM Blood Culture less useful Biopsy essential Longer treatment 6 months Caseating Granolumata on histology

Question 37

Risk factors for OM

Answer 37

- Diabetes - Old age - Peripheral vascular disease - Immunocompromise - Malnutrition - Trauma/ injury

Question 38

Non haematagenous spread

Answer 38

- occurs due to breakdown or removal of the normal protective barriers of skin and soft tissue or contiguous spread (e.g. local skin infection like cellulitis spreading to the bone). - **Open fractures** - **Skin ulcers** - **Surgery** - **Prosthesis** - **Trauma** - **Animal/ insect bites**

Question 39

Haematogenous spread

Answer 39

refers to the spread of a pathogen via the blood. Most commonly affects the axial skeleton, primarily the vertebral bones. After the vertebral bones the next most frequently affected sites are other axial bones like the sternum and pelvis. - **Indwelling intravascular catheter** (e.g. Hickman line) - **Haemodialysis** - **Endocarditis** - **IV drug use**

Question 40

Acute osteomyelitis

Answer 40

- Once the bacteria reach the bone they start to proliferate. This alerts nearby immune cells - specifically dendritic cells and macrophages - that try to fight off the infection. This represents the **acute phase** of the disease and occurs over a course of weeks. The immune cells release chemicals and enzymes that break down bone and cause local destruction. Usually acute osteomyelitis comes to a resolution - the immune system destroys all of the invading bacteria. - If the lesion is not that extensive, and there’s viable bone the osteoblasts and the osteoclasts begin to repair the damage over a period of weeks

Question 41

Chronic osteomyelitis

Answer 41

- affected bone sometimes becomes necrotic and separates from the healthy part of the bone - and that’s called a **sequestrum.** At the same time, the osteoblasts that originate from the periosteum may form new bone that wraps the sequestrum in place, this is called an **involucrum.** - **Cloaca** may also form