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
Hansen’s 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 IIIB
Type IIIA
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)
I:
II:
III:
IV:
1985
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
L
B : locally compromised
BS: systemically compromised
BC: 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 BS 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)
None
Pain
Tenderness
Fever
HA
Nausea/Vomiting
Erythema
Swelling
Sinus Tract
Drainage
Limp
Fluctuence
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
99M Tc
67Ga
111In
WBC
M
99
Tc
• Action
– binds to hydroxyapetite crystals
• Osteoblastic activity
– Demineralized bone
– Immature collagen
M
99
•
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
M
99
Tc: False Positive
DM foot d/o
Septic arthritis
Inflammatory bone dz
Adjacent to pressure sores
M
99
Tc
4 Phase Bone Scan
• New development
• Action:
– Mature bone: uptake stops at 4 hr
– Immature woven bone: cont’d uptake at 24 hr
• Problem: needs f/u imaging at 24 hr (compliance)
• Gupta 1988, Israel 1987, Schauwecker 1992
67Ga
• Exudation of in vivo labeled serum protein
– Transferrin, haptoglobin, albumin
• Results
– 81% sensitivity, 69% specificity
– Schauwecker, 1992
• Combination with Tc
–  sensitivity, but  specificity
111In
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
– T2
Dark
Bright/Mixed
T1 bright
T2 dark
T1 bright
T2 dark
MRI
• Acute:
–  marrow fat
–  granulation tissue H2O
• 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
S
K
A
P
E
Enterococcus faecuim
Staphlococcus aureus
Klebsiella pneumoniae
Acinobacter baumannii
Pseudomonas aeruginosa
Enterobacter aerogenes
MSSA & MRSA
• MSSA  Change to β lactam
• MRSA  Treat ≤ MIC
Gram Negative Rods - SPICE
S
P
I
C
E
Serratia
Pseudomonas
Indole positive
Citrobacter
Enterobacter
Gram
Negative
Rods
Proionibacterium acnes
• Axillary bacteria (sebaceous glands)
• Treated with:
– 1st: PCN or vanco
– 2nd: 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
Synercid
iv
 Infectious Disease Consult
↓ plts
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 BC
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 BS
Presentation
Initial Post op
3 mo
Exchange IMN at 4 ½ 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 BC 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 BC 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
All Patients
Healed
Infected
Nonunion
Additional
Procedures
Union at
final followup
Culture Positive
Culture
Negative
73%
95.8%
13%
4%
27%
4%
93%
100%
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.
2.
3.
Kelly II JD, Hobgood ER. Positive culture rate in revision shoulder arthroplasty. Clin Orthop Relat Res. 2009;467:2243-48.
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.
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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