B6.078 Osteomyelitis

Question 1

anatomic types of osteomyelitis

Answer 1

stage 1: medullary
stage 2: superficial
stage 3: localized
stage 4: diffuse

Question 2

physiologic classes of osteomyelitis

Answer 2

A host: normal
B host (s) : systemic compromise
B host (l) : localized compromise
B host (sl): systemic and local compromise
C host: treatment worse than disease

Question 3

systemic factors that affect osteomyelitis

Answer 3

malnutrition
renal or hepatic failure
DM
chronic hypoxia
immune disease
malignancy
extremes of age
immunosuppression or immune deficiency

Question 4

local factors that affect osteomyelitis

Answer 4

chronic lymphedema
major vessel compromise
small vessel compromise
vasculitis
venous stasis
extensive scarring
radiation fibrosis
neuropathy
tobacco abuse

Question 5

pathogenesis of osteomyelitis

Answer 5

compromised bone allows for bacterial attachment

Question 6

mediators of microbial adhesion

Answer 6

hematoma
fibrin
platelets
fibronectin

Question 7

forces that mediate adhesion of bacteria to bone

Answer 7

van der walls
hydrophobic interactions between small molecules
polysaccharide polymers

Question 8

bacterial progression of osteomyelitis

Answer 8

disruption of periosteum allows for blood collection around damaged bone
disruption of blood flow occurs within cortical bone
bone becomes walled off by bacteria/biofilm and no longer viable
over time, bone can extrude out of sinus tract

Question 9

what do bacteria in osteomyelitis release?

Answer 9

extracellular toxins
bacterial antigens / enzymes
this leads to recruitment of additional immune cells

Question 10

what causes the damage in osteomyelitis

Answer 10

immune response

granular enzymes can degrade bone and cartilage substrates such as collagen and elastin, leading to bone degradation

Question 11

granular enzymes

Answer 11

serine proteases
endogenous oxidants
metalloproteinases

Question 12

pathogenesis of osteomyelitis

Answer 12

1. pus spreads into vascular channels
2. increased intraosseous pressure, decreased blood flow, decreased pH, decreased O2
3. ischemic necrosis
4. formation of devascularized fragments

Question 13

what is hematogenous osteomyelitis

Answer 13

osteomyelitis spread via blood

Question 14

where does hematogenous osteomyelitis occur

Answer 14

metaphyses of long bones in children

vertebrae of adults

Question 15

why does hematogenous myelitis occur in metaphyses in children

Answer 15

non anastomosing capillary ends make sharp loops near growth plate
-blood pools and allows for movement of bacteria
metaphyseal capillaries lack phagocytic lining cells
sinusoidal veins contain functionally inactive phagocytic cells

Question 16

is acute vs chronic osteo an applicable designation

Answer 16

not really

areas of micronecrosis must be removed regardless of the acuity or chronicity of an uncontrolled infection

Question 17

how to diagnose osteomyelitis

Answer 17

isolate organism from bone
histo evidence of inflammation and osteonecrosis
exception: in hematogenous osteomyelitis blood cultures and radiographic evidence may be sufficient

Question 18

how to do a bone culture

Answer 18

take before abx initiated or once a person has been off abx for a sufficient period of time

• bone cultures taken during debridement surgery are preferred
• deep bone biopsy

Question 19

lab findings in osteomyelitis

Answer 19

non-specific
leukocytosis (acute): rarely >15,000
in chronic, WBC usually normal
increased ESR and CRP

Question 20

can you culture the drainage from the sinus tract

Answer 20

no, multiple other colonizing bacteria

Question 21

when can you see changes on xray in osteomyelitis?

Answer 21

1st visible change in bone: 2-3 weeks
lytic changes: weeks to months
need loss of 30-50% of bone mineralization to see changes

Question 22

early changes on imaging

Answer 22

soft tissue swelling
periosteal thickening, or elevation or both
focal osteopenia
loss of trabecular architecture

Question 23

later changes on imaging

Answer 23

diffuse osteopenia / lytic changes

Question 24

benefits of CT in imaging osteo

Answer 24

high spatial resolution
exceptional cortical bone density
small foci intraosseous gas
tiny foreign bodies
involucrum / sequestration formation

Question 25

benefits of bone scintigraphy in imaging osteo

Answer 25

MDP pools in areas with good blood flow positive in 24-48 hours after onset of disease can detect multiple areas of involvement good sensitivity

Question 26

mechanisms of bone scintigraphy

Answer 26

absorption on crystal surfaces binding to organic matrix preferentially incorporated into metabolically active bone

Question 27

normal bone scintigraphy

Answer 27

rapid redistribution throughout extracellular fluid over several hours, >50% accumulates in bone, remainder in urine symmetrical pattern

Question 28

benefits of MRI in imaging osteo

Answer 28

exquisite bone and soft tissue detail high sens and spec best imaging technique

Question 29

early osteo on MRI

Answer 29

poor definition soft tissue planes no cortical thickening interface normal / abnormal marrow difficult to appreciate

Question 30

chronic osteo on MRI

Answer 30

cortical thickening good distinction between normal / abnormal marrow Gd T1 enhanced images > no enhancement with devitalized sequestered tissue

Question 31

treatment of osteo in adults (non hematogenous)

Answer 31

surgical disease | 4-6 weeks parenteral abx + surgery

Question 32

principals of osteo treatment

Answer 32

``` debride necrotic tissue obliterate dead space stabilization soft-tissue coverage restore effective blood supply ```

Question 33

treatment of osteo in children (hematogenous)

Answer 33

4 wks therapy ( 2 IV and 2 po)

Question 34

how long doe sit take bone to revascularize after debridement

Answer 34

3-4 weeks

Question 35

what does a lack of osseous incorporation of joint after hardware placement signify

Answer 35

sign of early infection

Question 36

black halo around hardware on xray

Answer 36

bony lysis / death | usually result of infection

Question 37

growth of biofilm

Answer 37

1. attachment 2. growth within EPS (extracellular polymeric substances) to form complex 3D structures that contain nutrients 3. dispersal of metabolically active bacteria from inside biofilm

Question 38

why cant antimicrobials treat biofilms well?

Answer 38

resistance to phagocytosis slowed metabolism of pathogens within biofilms decreased penetration of antimicrobial into biofilm

Question 39

discuss bacterial gene expression changes in biofilm states

Answer 39

12% genes differentially expressed | 6% upregulated, 6% downregulated

Question 40

downregulated genes within biofilm bacteria

Answer 40

``` translation, transcription adhesion factors aerobic production of energy phenol soluble modulins *stop dividing to be elusive to abx, and transition to anaerobic state to decrease metabolic activity) ```

Question 41

upregulated genes within biofilm bacteria

Answer 41

``` chaperones and stress factors fermentation global regulators resistance factors osmoprotection *keep organisms alive/viable long term in decreased metabolic state* ```

Question 42

why cant we cure chronic osteo with abx alone?

Answer 42

abx fairly ineffective against sessile organisms in biofilm biofilm can act as a diffusion barrier to slow down the infiltration of some antimicrobial agents biofilm protects host from phagocytic clearance reactive chlorine species may be deactivated in the surface layers of biofilm before deeper dissemination into lower layers

Question 43

what is bone cement?

Answer 43

polymerized polymethylmethacrylate drug delivery device (antibiotics can be added to cement) fills dead space exothermic reaction limits abx options

Question 44

use of rifampin in osteo

Answer 44

controversial has bactericidal activity, concentrates intracellularly and penetrates biofilm may be benefits for use in treatments of prosthetic device infections

Question 45

benefits of increased O2 tension

Answer 45

lethal effect on strict anaerobes augments oxygen dependent intracellular killing mechanisms benefits not clear in osteo, reserved for select really bad disease or as an adjunct to suppressive therapy

Question 46

osteo in the setting of vascular insufficiency

Answer 46

distal extremity most commonly involved usually diabetics (peripheral neuropathy) usually polymicrobial adequate blood flow required for healing

Question 47

clinical presentation of osteo in vascular insufficiency

Answer 47

pain often absent fever / systemic symptoms often lacking poor distal pulses

Question 48

pathogenesis of vertebral osteomyelitis

Answer 48

typically hematogenous seeding via arterial blood supply vertebral bone = highly vascular marrow with relatively high-volume blood flow compared to adult long bones arterial anastomoses extend into intervertebral discs > with age, end anastomoses regress, terminate in endplates blood flow sluggish near endplates

Question 49

characterize vertebral osteo

Answer 49

increasing incidence with age s. aureus most common GNRs - 30% (e.coli)

Question 50

locations of vertebral osteo

Answer 50

lumbar - 50% thoracic - 35% cervical - less common sacrum - more typical with contiguous infection

Question 51

diagnosis of vertebral osteo

Answer 51

usually a single organism present blood cultures positive 50-70%, obviating need for biopsy MRI very sensitive for discitis, epidural abscess, marrow edema, etc. (can estimate degree of bony destruction)

Question 52

treatment of vertebral osteo

Answer 52

6 weeks of parenteral or highly bioavailable oral therapy for most patients

Question 53

factors associated with poor outcomes in vertebral osteo

Answer 53

``` multidisc disease epidural abscess lack of surgical therapy s. aureus old age extensive bony destruction ```

Question 54

indications for surgery in vertebral osteo

Answer 54

progressive neuro deficits progressive deformity / spinal instability persistent or recurrent bloodstream infection worsening pain despite appropriate therapy

Question 55

follow up MRI in vertebral osteo

Answer 55

not routinely recommended if improving | only in patients with poor clinical response