Osteomyelitis:

Pathophysiology &
Treatment Decisions
Clifford B. Jones, MD

Original Author: Clifford B. Jones, MD; March 2004
Revised February 2007 & February 2011

One Should Especially Avoid Such
Cases if One has a Respectable
Excuse, for the Favorable Chances are
Few and the Risks are Many.
.Besides, if a Man does not Reduce the
Fracture, He will be Thought Unskillful. If
He does Reduce It, He will bring the Patient
Nearer to Death than Recovery.

Hippocratic Writings, New York, Pelican Books, 1978
Fracture Management Goals
1. Osseous Union
2. Restore Limb Function
3. Avoid Complications
Osteomyelitis Results in:
1. Reduction in limb function
2. Psychological & Social dysfunction
3. Increased cost
Hansens 7 Ds
Concerning Prolonged Orthopaedic Problems
Despair
Divorce
Destitute
Depression
Delinquency
Default
Death
Sigvard Ted Hansen, 1997
Introduction
350,000 long bone fxs/yr
Infection risk varies:
Type I open 10/1,000 infections
Type III open up to 25%
Gustilo Open Fx Class
JBJS, 72A: 299-303, 1990





2%
7%
7%
10-50%
25-50%
Open Fractures
Type II
Type IIIA
Type IIIB Type IIIB
Negative Biology of Open Fx
Contamination
Crushing
Stripping
Devascularization
Comminution
Blood Supply
Rhinelander, CORR, 1974
Blood Supply
Rhinelander, CORR, 1974
Normal - endosteal/medullary 2/3-3/4
internal external

Fracture - periosteal/external majority
internal external
Periosteal Blood Supply Important
Centripetal Flow
Rhinelander, CORR, 1974
Initial Emergent Treatment
dT
Antibiotics, IV
Reduce
Stabilize
Cover wound
Why infection risk high?
Infection risk Fracture type (soft tissue)

Open fx = Contamination (70% cx +)

Open fx = Infected fx > 8 hours
Cost Analysis
Infection
Increase cost 16-21%/pt
Increase hosp stay 36-50%/pt
Total Cost $ 271 million/yr
Definition
Group of conditions
presence of bacteria & an
inflammatory response causing
progressive destruction of bone.
Fears, RL, et al, 1998
suppurative process in bone caused
by a pyogenic organism
Pelligrini, VD, et al, 1996
Why destruction of bone
matrix?
Proteolytic enzymes
Hyperemia
Osteoclasts
Do Not Delay Tx & Dx
Classification
Waldvogel, 1971
Classification based on pathogenesis
May, 1989
5 parts, post-traumatic tibial osteomyelitis
Cierny & Mader, 1985
4 factors affecting outcome
Host, site, extent of necrosis, degree of impairment
Pathogenesis
Waldvogel, 1971
1. Hematogenous
2. Contiguous focus of infection
3. Direct inoculation
Anatomic
Classification
(Cierny-Mader)
1985
I: II:
III: IV:
Classification Break-Down
I. Medullary
Endosteal nidus, min soft tissue involvement, ? Sinus tract
II. Superficial
Surface of bone, usu 2 to soft tissue defect
III. Localized
Localized sequestra, usu sinus tract,
Usu stable s/p excision
IV. Diffuse
Permeative process, combination of I/II/III,
Usu Unstable s/p excision
Physiologic Classification
(Cierny-Mader, 1985)
A-Host: Good immune system & delivery

B-Host: Compromised host
B
L
: locally compromised
B
S
: systemically compromised
B
C
: combined

C-Host: Requires suppressive or no Tx
Minimal disability
Tx worse than dz, not a surgical candidate
Clinical Staging
(Cierny-Mader, 1985)
Anatomic Type
+ Clinical Stage
Physiologic Class
Example: IV B
S
tibial osteomyelitis = diffuse tibial lesion in a systemically
compromised host
Types of Pathophysiology
Acute/Hematogenous

Chronic/Nonhematogenous
Acute/Hematogenous
Anatomy (Hobo)
Sharp twist in metaphyseal capillaries
Stasis (Trueta)
Decreased flow in capillaries & veins
Combination (Morrissy)
Trauma & Bacteria
Acute/Hematogenous
Progression of Dz
Cell death 2 to bacterial exotoxins
bacterial culture medium
worsens condition
Vascularity, leukocytosis, edema
Pressure w/in rigid osseous container
Pain, swelling, erythema
Potential for septic arthritis (knee, hip, shoulder)
Chronic/Nonhematogenous
S. aureus
Pseudomonas aureginosa
Enterobacter

> 30% Polymicrobial
Clinical Findings
(varied)
Erythema
Swelling
Sinus Tract
Drainage
Limp
Fluctuence
None
Pain
Tenderness
Fever
HA
Nausea/Vomiting
Clinical Findings
Must have high index of suspicion
Inappropriate use of Abx obscure Sx
Must obtain Dx quickly
If Tx started < 72:
Decrease incidence of chronic osteomyelitis
Decrease destruction of bone
Laboratory Data
Acute (Morrey, BF, OCNA, 1975)
WBC (25% of time)
Abnormal differential, Left Shift (65%)
Blood Cx 50% positive
Chronic
Mild anemia, WESR, C-reactive protein
Possible leukocytosis with L shift
Blood Cx usually negative
Radiographs
Early usu negative

Changes delayed (10-21 days)
Radiographs
Soft Tissue
Swelling, obscured soft tissue planes,
haziness
Osseous
Hyperemia, demineralization
Lysis (when > 40% resorbed)
Periosteal reaction
Sclerosis (late)
Radionucleotide Imaging
99
M
Tc

67
Ga

111
In WBC

99
M
Tc

Action
binds to hydroxyapetite crystals
Osteoblastic activity
Demineralized bone
Immature collagen
99
M
Tc

3 Phase Bone Scan
1. Radionucleotide angiogram
2. Immediate post injection blood pool
3. Three hour: soft tissue, urinary excretion
Diagnosis
Cellulitis: Phases 1 &2, no change 3
Osteomyelitis: Phases 1 & 2, focal 3
Results: 94% sensitivity, 95% specificity
Rosenthal 1992, Schauwecker 1992
Cellulitis
Osteomyelitis
99
M
Tc: False Positive

DM foot d/o
Septic arthritis
Inflammatory bone dz
Adjacent to pressure sores
99
M
Tc

4 Phase Bone Scan
New development
Action:
Mature bone: uptake stops at 4 hr
Immature woven bone: contd uptake at 24 hr
Problem: needs f/u imaging at 24 hr (compliance)
Gupta 1988, Israel 1987, Schauwecker 1992
67
Ga

Exudation of in vivo labeled serum protein
Transferrin, haptoglobin, albumin
Results
81% sensitivity, 69% specificity
Schauwecker, 1992
Combination with Tc
sensitivity, but specificity
111
In WBC


Used in combination (Seabold, 1989)
In/Tc: 88% accurate
Ga/Tc: 39% accurate
Preparation problem
rad dose to spleen, 18-24hr delay
Spine (Whalen, Spine 1991)
83% false negative use MRI
MRI
No radiation
Good soft tissue imaging
Imaging:
T1 Dark
T2 Bright/Mixed
T1 bright
T2 dark
T1 bright T2 dark
MRI
Acute:
marrow fat
granulation tissue H
2
O
Chronic: thickened cortex
Low signal on all scans
Cellulitis: no marrow changes
MRI Results
Schauwecker, 1992
Sensitivity 92-100%
Specificity 89-100%
Excellent for Spine (Modic, RCNA, 1986)
Sens 96%, Spec 92%, Accuracy 94%
Soft tissue extension
Sinus tract formation
Bright Tx from skin to bone
CT Imaging
Image cortical and cancellous bone

Evaluate osseous adequacy of debridement
Aspiration Biopsy
Acute
Good, only 10-15% false negative
Chronic
Sinus tract cx: 76% sens, 80% spec
70% with S aureus & Enterococcus
30% Pseudomonas
Does not determine correct Abx
Acute/Hematogenous
Changing Bacterial
Pathogens
Resistant Bacterium - ESKAPE
E Enterococcus faecuim
S Staphlococcus aureus
K Klebsiella pneumoniae
A Acinobacter baumannii
P Pseudomonas aeruginosa
E Enterobacter aerogenes
MSSA & MRSA
MSSA Change to lactam

MRSA Treat MIC
Gram Negative Rods - SPICE
S Serratia
P Pseudomonas
I Indole positive
C Citrobacter
E Enterobacter
Gram
Negative
Rods
Proionibacterium acnes
Axillary bacteria (sebaceous glands)
Treated with:
1
st
: PCN or vanco
2
nd
: Macrolides & Fluoroquinolones
Long incubation time
Call lab culture 2 wks, gram positive rods
Especially important for shoulder:
Nonunions
Infections
Multilocus Polymerase Chain reaction &
Electrospray Ionization/Mass Spectrometry
Bacterial or fungal DNA is amplified by
polymerase chain reaction and introduced
into a mass spectroscopy by electrospray
ionization
The amplification procedure uses 16 S
primers, and the primers can be varied to
detect fungi and antibiotic resistance genes
(eg, mec A).
Multilocus Polymerase Chain reaction &
Electrospray Ionization/Mass Spectrometry
Although culturing bacteria takes days,
amplifying DNA takes hours
Accurate, rapid point-of-care devices would
be ideal for clinical use
Treatment Preventation
Antibiotics correct organism
Debridement until viable tissue obtained
Irrigation
Wound care/coverage
Osseous & soft tissue stability
Fx stability
Dead space management
New Oral Agents: MRSA
Zyvox/linazid po/iv plts

Synercid iv

Infectious Disease Consult
Stability Oxymoron
Hardware increased bacterial growth

&

Fracture stability (hardware) bacterial growth
Glycocalyx = slime
Remove hardware, exchange for new once infection under control
Dead Space Control
Abx IMN Materials & Methods
Research: Retrospective Review
Time: 3 year period, 2 year F/U
Location: Level 1 Trauma Center
Patients
Age: 37 (range 18-67)

Femurs (n=4)
Closed n=2
Open n=2
Tibia (n=28)
Closed n=2
Open n=26
II: 4/26
IIIA: 12/26
IIIB: 10/28
10/28 open tibial fx with rotational or FTT for coverage
Antibiotic Nail
Inserted Avg. 3 mo. (range 2 day 23 mo.)
2 bags PMMA
2.O g Vancomycin
2.4 g Tobramycin
32 Fr Chest Tube
3.2 mm Guide Wire
Incise & Debride Wound
I&D Wound
I&D Canal
Reamers, Vent Hole
Presentation
44 M
4 bacterium
Coccidiomycosis
2 prior known flare ups
Antibiotic IMN
32 Fr Chest Tube
2 bags PMMA
2.0 Vancomycin
2.4 Tobramycin

Insert under pressure into chest tube
while still wet

Insert 3.2 mm ball tip guide rod

Remove plastic before PMMA too hot
and melting plastic chest tube
Insert Abx
IMN
Wait until IMN Insertion
Wound Healed
Labs Improved
Anabolic Host
Usually 4-8 wks

(Average 4-8 wks)
Example
Infected Tibial Nonunion
32 M
2 ppd smoker
MCA 18 mo, 2 prior surgeries
Draining wound
No one to take care of him
Translation No money
Presentation
Options
Type IV B
C
Unstable with Osteo
Smoker, malnutrition
Local open wound
Nothing
Revise with plate
Revise with nail
Revise with ex fix
Revise with Ilizarov
Amputation

Length +/-
Debridement of Skin & Bone
Dead Space Management
Stabilize Nonunion
Coverage of Wound
Lengthening Leg
Noncompliance - Nonunion
Final Healed with Grafting
Infected Tibial Nonunion
38 yo M
Snuff tobacco
1 pint vodka/day
6 mo MCA with IIIB open tibia

Type I B
S
Presentation
Initial Post op
3 mo
Exchange IMN at 4 mo
Final at 18 mo
Example
54 yo Male
Post-operative Pseudomonas osteomyelitis
Refractory to HW removal & Ancef
Healthy, non-smoking
Cierny III A Host



Photos from M Swiontkowski
Example 1
Dead Space


Calcaneal defect
Example 1
Debridement of all non-viable bone with
laser doppler
Defect filled with antibiotic PMMA
6 wks antibiotics
Example 1, at 6 wks
Removal Abx beads
Bone grafting
Lateral arm flap
Infection eradication
Example
47 yo Male, smoker
Presentation 2 months s/p ORIF closed proximal
tibia fx
Draining wound
Exposed HW
Cierny III B
C
Host


Photos from M Swiontkowski
Example
Debridement
HW remains
Abx beads

Exposed plate
Example
Gastrocnemeus flap, STSG
Example
At 6 weeks
Remove Abx beads
Bone grafting
Healed wound and fracture
Example
At 5 yo, tibial osteomyelitis
Partially treated
At 62 yo, presentation to MD
Chronic draining tibial osteomyelitis
Cierny III B
C
Host


Photos from M Swiontkowski
Example
Sinus tracts
Chronic skin changes
Example

I&D to normal bleeding
bone with laser doppler
Bx negative for cancer
Example
Abx beads
Latissimus Flap
STSG
Example
Removal Abx beads at 6 wks
No bone graft low demand
patient
Dz free at 8 years (70 yo)
The Fate of Patients with a
Surprise Positive Culture
After Nonunion Surgery
Olszewski D, Stucken C, Tornetta III P, Ricci W, Struebel
P, Jones C, Sietsema D
Results
460 patients
Two cohort groups
98 cultures (21%) surprise positive
362 cultures (79%) negative
Bacteria
Type of Bacteria Number
Coagulase-negative Staphylococcus 45
Methicillin-resistant S. Aureus 12
Pseudomonas 8
Proprionibacterium 8
Methicillin-sensitive S. Aureus 7
Bacillus 4
Peptostreptococcus 3
Staph species unspecified 3
Enterococcus 2
Strep viridans 2
Clostridium 2
E. coli, Staph epidermidis, Beta hemolytic strep,
Serratia, Candida and Aspergillus 1
Positive Cultures
98 with positive cultures
90 treated with antibiotics
6 8 week duration
Culture specific
8 patients not treated
Presumed contaminant
Union After Index
Culture (+) = 66 / 90 (73%)
Culture (-) = 347 / 362 (96%)
P < 0.0001
Infection After Index
Culture (+) = 11 / 90 (12%)
Culture (-) = 15 / 362 (4%)
P < 0.0001
Final Outcome
Culture (+) = 86 / 90 (95.5%)
24 Additional procedures
9 / 13 Debridement only
4 / 13 with 1 additional procedure
4 / 90 (4.5%) infected nonunion
2 BKA
Culture (-) = 362 / 362 (100%)
15 Additional procedures
P < 0.0001
Presumed Contaminants
8 surprise cultures not treated with antibiotics
Deemed contaminants
5 Healed
3 Nonunions
1 Amputation
1 Infected nonunion
1 Non-infected nonunion
Culture Positive Culture
Negative
Healed
73% 95.8%
Infected
Nonunion
13% 4%
Additional
Procedures
27% 4%
Union at
final follow-
up
93% 100%
All Patients
Summary
21% of 460 at risk nonunions had surprise
positive culture
Staph species
90 of 98 treated with antibiotics
Summary
Culture positive
73% Index
93% Final
Culture negative
95.5% Index
100% Final
Surprise cultures
Revision shoulder arthroplasty
17 to 29% surprise positives
13 to 25% require re-revision
Revision hip arthroplasty
11% surprise positives
13% require re-revision
1. Kelly II JD, Hobgood ER. Positive culture rate in revision shoulder arthroplasty. Clin Orthop Relat Res. 2009;467:2243-48.
2. Topolski MS, Chin PY, Sperling JW, Cofield RH. Revision shoulder arthroplasty with positive intraoperative cultures: the value of preoperative
studies and intraoperative histology. J Shoulder Elbow Surg. 2006;15:402-406.
3. Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty: a study of the treatment of one hundred and six infections. J Bone
Joint Surg Am. 1996;78:512-523.
Conclusions
21% surprise positive cultures
74% heal after initial index
procedure
26% required additional procedures
Recommendations
Counsel patients
Treat all positive cultures
Potentially offer two-stage procedures
Unknown efficacy
79% would be unnecessary

Conclusion
Prevention
Early Dx
Early Tx
Stabilize
Convert to Union ASAP
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