G19 Osteomyelitis

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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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