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Osteomyelitis:Pathophysiology &
Treatment Decisions
Clifford B. Jones, MD
Original Author: Clifford B. Jones, MD; March 2004Revised February 2007 & February 2011
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One Should Especially Avoid Such
Cases if One has a Respectable
Excuse, for the Favorable Chances are
Few and the Risks are Many.
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.Besides, if a Man does not Reduce the
Fracture, He will be Thought Unskillful. If
He does Reduce It, He will bring the PatientNearer to Death than Recovery.
Hippocratic Writings, New York, Pelican Books, 1978
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Fracture Management Goals
1. Osseous Union
2. Restore Limb Function
3. Avoid Complications
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Osteomyelitis Results in:
1. Reduction in limb function
2. Psychological & Social dysfunction
3. Increased cost
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Hansens 7 DsConcerning Prolonged Orthopaedic Problems
Despair
DivorceDestitute
Depression
Delinquency
Default
Death Sigvard Ted Hansen, 1997
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Introduction 350,000 long bone fxs/yr
Infection risk varies:
Type I open10/1,000 infections
Type III openup to 25%
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Gustilo Open Fx ClassJBJS, 72A: 299-303, 1990
2%
7%
7%
10-50%
25-50%
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Open Fractures
Type II
Type IIIA
Type IIIB Type IIIB
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Negative Biology of Open Fx
Contamination
Crushing
Stripping
Devascularization
Comminution
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Blood SupplyRhinelander, CORR, 1974
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Blood SupplyRhinelander, CORR, 1974
Normal - endosteal/medullary 2/3-3/4
internal external
Fracture- periosteal/external majority
internal external
Periosteal Blood Supply Important
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Centripetal FlowRhinelander, CORR, 1974
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Initial Emergent Treatment
dT
Antibiotics, IV
Reduce
Stabilize
Cover wound
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Why infection risk high?
Infection risk Fracture type (soft tissue)
Open fx = Contamination (70% cx +)
Open fx = Infected fx > 8 hours
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Cost Analysis
Infection
Increase cost 16-21%/pt
Increase hosp stay 36-50%/pt
Total Cost $ 271 million/yr
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Definition
Group of conditions
presence of bacteria & an
inflammatory response causingprogressive destruction of bone.
Fears, RL, et al, 1998
suppurative process in bone causedby a pyogenic organism
Pelligrini, VD, et al, 1996
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Why destruction of bone
matrix?
Proteolytic enzymes
Hyperemia
Osteoclasts
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Do Not Delay Tx & Dx
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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
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PathogenesisWaldvogel, 1971
1. Hematogenous
2. Contiguous focus of infection
3. Direct inoculation
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AnatomicClassification
(Cierny-Mader)1985
I: II:
III: IV:
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Classification Break-Down
I. MedullaryEndosteal nidus, min soft tissue involvement, ? Sinus tract
II. SuperficialSurface of bone, usu 2to soft tissue defect
III. LocalizedLocalized sequestra, usu sinus tract,
Usu stables/p excision
IV. DiffusePermeative process, combination of I/II/III,
Usu Unstable s/p excision
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Physiologic Classification(Cierny-Mader, 1985)
A-Host: Good immune system & delivery
B-Host: Compromised hostB
L: locallycompromised
BS:systemicallycompromised
BC: combined
C-Host: Requires suppressive or no TxMinimal disability
Tx worse than dz, not a surgical candidate
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Clinical Staging(Cierny-Mader, 1985)
Anatomic Type
+ Clinical Stage
Physiologic ClassExample: IV B
Stibial osteomyelitis = diffuse tibial lesion in a systemically
compromised host
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Types of Pathophysiology
Acute/Hematogenous
Chronic/Nonhematogenous
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Acute/Hematogenous
Anatomy (Hobo)
Sharp twist in metaphyseal capillaries Stasis (Trueta)
Decreased flow in capillaries & veins
Combination (Morrissy)Trauma & Bacteria
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Acute/Hematogenous
Progression of Dz
Cell death 2to bacterial exotoxins
bacterial culture mediumworsens condition
Vascularity, leukocytosis, edema
Pressure w/in rigid osseous containerPain, swelling, erythema
Potential for septic arthritis (knee, hip, shoulder)
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Chronic/Nonhematogenous
S. aureus
Pseudomonas aureginosa
Enterobacter
> 30% Polymicrobial
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Clinical Findings
(varied)Erythema
Swelling
Sinus Tract
Drainage
Limp
Fluctuence
None
Pain
Tenderness
Fever
HA
Nausea/Vomiting
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Clinical Findings
Must have high index of suspicion
Inappropriate use of Abxobscure Sx
Must obtain Dx quickly
If Tx started < 72:
Decrease incidence of chronic osteomyelitis
Decrease destruction of bone
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Laboratory Data
Acute (Morrey, BF, OCNA, 1975)
WBC (25% of time)
Abnormal differential, Left Shift (65%)Blood Cx50% positive
Chronic
Mild anemia, WESR, C-reactive protein
Possible leukocytosis with L shift
Blood Cxusually negative
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Radiographs
Earlyusu negative
Changesdelayed (10-21 days)
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Radiographs
Soft Tissue
Swelling, obscured soft tissue planes,
haziness
Osseous
Hyperemia, demineralization
Lysis (when > 40% resorbed)
Periosteal reaction
Sclerosis (late)
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Radionucleotide Imaging
99MTc
67Ga
111In WBC
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99MTc
Action
binds to hydroxyapetite crystals
Osteoblastic activity
Demineralized bone
Immature collagen
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99MTc
3 Phase Bone Scan1. 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
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Cellulitis
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Osteomyelitis
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99MTc: False Positive
DM foot d/o
Septic arthritisInflammatory bone dz
Adjacent to pressure sores
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99MTc
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
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67Ga
Exudation of in vivo labeled serum protein
Transferrin, haptoglobin, albumin
Results
81% sensitivity, 69% specificity Schauwecker, 1992
Combination with Tcsensitivity, but specificity
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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 negativeuse MRI
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MRI
No radiation
Good soft tissue imaging
Imaging:
T1 Dark
T2 Bright/Mixed
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T1 bright T2 dark
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T1 bright T2 dark
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MRI
Acute:
marrow fat
granulation tissue H2O
Chronic: thickened cortex
Low signal on all scans Cellulitis: no marrow changes
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MRI ResultsSchauwecker, 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
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CT Imaging
Image cortical and cancellous bone
Evaluate osseous adequacy of debridement
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Aspiration Biopsy
Acute
Good, only 10-15% false negative
ChronicSinus tract cx: 76% sens, 80% spec
70% with S aureus&Enterococcus
30%Pseudomonas
Does not determine correct Abx
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Acute/Hematogenous
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Changing Bacterial
Pathogens
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Resistant Bacterium - ESKAPE
E Enterococcus faecuim
S Staphlococcus aureusK Klebsiella pneumoniae
A Acinobacter baumannii
P Pseudomonas aeruginosaE Enterobacter aerogenes
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MSSA & MRSA
MSSAChange to lactam
MRSATreat MIC
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Gram Negative Rods - SPICE
S Serratia
P Pseudomonas
I Indole positive
C Citrobacter
E Enterobacter
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Gram
NegativeRods
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Proionibacterium acnes
Axillary bacteria (sebaceous glands)
Treated with:
1st: PCN or vanco
2nd: Macrolides & Fluoroquinolones
Long incubation time
Call labculture 2 wks, gram positive rods
Especially important for shoulder:
Nonunions
Infections
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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 electrosprayionization
The amplification procedure uses 16 S
primers, and the primers can be varied todetect fungi and antibiotic resistance genes
(eg, mec A).
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Multilocus Polymerase Chain reaction &
Electrospray Ionization/Mass Spectrometry Although culturing bacteria takes days,
amplifying DNA takes hours
Accurate, rapid point-of-care devices wouldbe ideal for clinical use
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Treatment Preventation
Antibioticscorrect organism
Debridementuntil viable tissue obtained
Irrigation
Wound care/coverage
Osseous & soft tissue stability
Fx stability
Dead space management
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New Oral Agents: MRSA
Zyvox/linazid po/iv plts
Synercid iv
Infectious Disease Consult
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Stability Oxymoron
Hardware increased bacterial growth
&
Fracture stability (hardware) bacterial growth
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Glycocalyx = slime
Remove hardware, exchange for new once infection under control
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Dead Space Control
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PatientsAge: 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
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Antibiotic Nail
Inserted Avg. 3 mo. (range 2 day23 mo.)
2 bags PMMA
2.O g Vancomycin
2.4 g Tobramycin
32 Fr Chest Tube
3.2 mm Guide Wire
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Incise & Debride WoundI&D Wound
I&D Canal
Reamers, Vent Hole
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Presentation
44 M
4 bacteriumCoccidiomycosis
2 prior known flare ups
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Antibiotic IMN
32 Fr Chest Tube2 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
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Insert Abx
IMN
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Wait until IMN Insertion
Wound Healed
Labs ImprovedAnabolic Host
Usually 4-8 wks
(Average 4-8 wks)
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Example
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Infected Tibial Nonunion
32 M
2 ppd smoker
MCA 18 mo, 2 prior surgeries
Draining wound
No one to take care of him
TranslationNo money
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Presentation
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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 +/-
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Stabilize Nonunion
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Coverage of Wound
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Lengthening Leg
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Noncompliance - Nonunion
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FinalHealed with Grafting
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Infected Tibial Nonunion
38 yo M
Snuff tobacco
1 pint vodka/day
6 mo MCA with IIIB open tibia
Type I BS
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Presentation
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Initial Post op
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3 mo
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Exchange IMN at 4 mo
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Final at 18 mo
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Example
54 yo Male
Post-operativePseudomonasosteomyelitis
Refractory to HW removal & Ancef
Healthy, non-smoking
Cierny III A Host
Photos from M Swiontkowski
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Example 1
Dead Space
Calcaneal defect
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Example 1
Debridement of all non-viable bone with
laser doppler
Defect filled with antibiotic PMMA 6 wks antibiotics
E l 1 t 6 k
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Example 1, at 6 wks
Removal Abx beads
Bone grafting
Lateral arm flap Infection eradication
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Example
47 yo Male, smoker
Presentation 2 months s/p ORIF closed proximaltibia fx
Draining wound
Exposed HW
Cierny III BCHost
Photos from M Swiontkowski
E l
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Example
Debridement
HW remains
Abx beads
Exposed plate
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Example
Gastrocnemeus flap, STSG
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Example
At 6 weeks
Remove Abx beads
Bone grafting
Healed wound and fracture
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Example
At 5 yo, tibial osteomyelitis
Partially treated
At 62 yo, presentation to MD Chronic draining tibial osteomyelitis
Cierny III BCHost
Photos from M Swiontkowski
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Example
Sinus tracts
Chronic skin changes
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ExampleI&D to normal bleeding
bone with laser doppler
Bxnegative for cancer
Example
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Example
Abx beads
Latissimus Flap
STSG
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Example
Removal Abx beads at 6 wks
No bone graftlow demand
patient Dz free at 8 years (70 yo)
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The Fate of Patients with a
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Surprise Positive Culture
After Nonunion Surgery
Olszewski D, Stucken C, Tornetta III P, Ricci W, StruebelP, Jones C, Sietsema D
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Results
460patients
Two cohort groups
98 cultures (21%) surprise positive
362 cultures (79%) negative
Bacteria
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Type of Bacteria Number
Coagulase-negative Staphylococcus 45
Methicillin-resistant S. Aureus 12
Pseudomonas 8
Proprionibacterium 8
Methicillin-sensitive S. Aureus 7Bacillus 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
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Union After Index
Culture (+) = 66 / 90 (73%)
Culture (-) = 347 / 362 (96%)
P < 0.0001
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Infection After Index
Culture (+) = 11 / 90 (12%)
Culture (-) = 15 / 362 (4%)
P < 0.0001
Final Outcome
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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
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Presumed Contaminants
8 surprise cultures not treated with antibiotics Deemed contaminants
5 Healed
3 Nonunions
1 Amputation
1 Infected nonunion
1 Non-infected nonunion
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Culture Positive Culture
Negative
Healed 73% 95.8%
InfectedNonunion
13% 4%
Additional
Procedures27% 4%
Union at
final follow-
up93% 100%
All Patients
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Summary
21% of 460 at risk nonunions had surprise
positive culture
Staph species 90 of 98 treated with antibiotics
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Surprise cultures
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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.
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Conclusions
21% surprise positive cultures
74% heal after initial index
procedure
26% required additional procedures
i
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Recommendations
Counsel patients
Treat all positive cultures
Potentially offer two-stage proceduresUnknown efficacy
79% would be unnecessary
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