Osteomyelitis

Objectives

• Epidemiology• Major classification systems and types • Pathogenesis, Microbiology• Clinical Manifestations• Diagnosis• Treatment

Epidemiology

• Incidence of acute osteomyelitis– 10 per 100,000 in Sweden– Higher incidence in warm and humid climates and

lower socioeconomic areas

• Incidence of chronic osteomyelitis– Estimated to be 15-30 per 100,000 over the last

10 years

Epidemiology

• Prosthetic implants– 1.8 million prosthetic joint implants and 2 million

devices for hip fractures per year– In the 1970’s, 10% of all major hip procedures

involving an implant resulted in infection– Currently, antibiotic prophylaxis has decreased

infection rates to <1% in hip and 2% in knee prosthetic surgery

– HOWEVER prosthetic joint implants remain the most common cause of joint infections

• 1-2% for total knee and hip arthroplasty

ClassificationCierny and Mader Classification SystemBased on:

Affected portion of the bone - “Stages”Physiologic status of the host – “Classes”Factors affecting the local environment

Combines 4 anatomic “stages” with three physiologic host “categories”12 possible combinations

Lends itself to the treatment and prognosis of osteomyelitisE.g. stage 1 (medullary osteomyelitis) can usually be

treated with antibiotics alone

Cierny and Mader Classification

Classification

• Waldvogel Classification System– Based on PATHOGENIC mechanisms of infection

• Waldvogel System– Hematogenous osteomyelitis

• Acute vs chronic– Contiguous focus osteomyelitis – soft tissue

infection, abcess, prosthesis• Vascular insufficiency (DM, PVD)• Without vascular insufficiency (trauma, prosthesis)

– Acute vs chronic

Pathophysiology

• Progressive infection of bone– Inflammatory destruction– New bone formation

• Three major categories (Waldvogel)– Contiguous focus without vascular insufficiency

• Trauma, surgery, prosthesis– Contiguous focus with vascular insufficiency

• DM or PVD– Hematogenous spread

PathophysiologyACUTE

Bacterial seeding, suppurative infectionVascular compromise

Pre-existing – DM or PVDTraumatic – disruption due to traumaAs a consequence of osteomyelitis

Acute suppurative infection = edema , increased intramedullary pressure = loss of medullary and periosteal blood supply

CHRONICAvascular areas of infection with necrotic bone

Nidus of dead bone refractory to clinical care

Pathophysiology: Acute vs. Chronic

• Chronic Osteomyelitis– Dead bone (sequestrum)– Bony encasement of the sequestrum(involucrum)– Local bone loss– Persistent drainage and/or sinus tracts

Clinical Manifestations• Acute – gradual onset over days

– Typical: dull pain with or without movment– Other (some, all, or none…)

• Local findings (tenderness, warmth, erythema, swelling)• Systemic findings (fever / chills)

– Hip, vertebrae, pelvis with fewer SXs – Septic arthritis – knee, hip, shoulder

• Subacute and chronic – mild pain over several weeks

• Chronic - sinus tracts, prosthesis, chronic soft tissue ulceration (DM)

Hematogenous Osteomyelitis

• Disease of children– 20% of all adult osteo cases– 85% of hematogenous osteo cases in pts < 17

• M:F 2:1 for unknown reasons• Site of infection varies with age

– Children: metaphyses of long bones– Adults: vertebrae > clavicles, pelvis/SI, long bones

• Predilection for specific sites based on blood supply

Blood Supply Based on Age

osteo-bloodsupply.jpg

Hematogenous Osteomyelitis

osteo-bloodsupply2.jpg

Hematogenous Osteomyelitis

• Risk factors:– IVDU, central lines, HD, urethral catheters, sickle

cell disease• Adult long bone

– Diaphysis with extension• May enter joint -> septic arthritis• Sinus tracts -> adherent periosteum

• Ususally monomicrobial– Staph aureus

Hematogenous Osteomyelitis: Infecting Organisms

Infants Children AdultsStaph aureus Staph aureus Staph aureusStrep agalactiae Strep pyogenesE. coli H. influenzae

Microorganisms Associated with Certain Conditions

Lancet 2004 364:369-79.

• Sickle cell- Salmonella, S pneumoniae

• HIV- Bartonella henselae, B quintana

• Human or animal bites- Pasteurella multocida, Eikenella corrodens

• Foreign-body – coag (-) Staph, Proprionibacterium sp

• Immunocompromised- Aspergillus sp, Candida albicans

• IVDU: Pseudomonas, Serratia m, Tb

Hematogenous Osteomyelitis: Clinical Presentation

• Neonatal– Paucity of systemic and local findings– Edema and decreased motion of a limb

• Children– Abrupt fever, irritability, lethargy– Local signs of inflammation

• Adults– Nonspecific pain and few constitutional symptoms– Occasional acute presentations

Vertebral Osteomyelitis

• Route of infection most often hematogenous• Disease of adults• Increasing incidence• Route of infection: segmental arteries

– Freq involvement of 2 adjacent vertebrae and disk due to bifurcation of the artery

• Microbiology:– Staph aureus > 50%– Enteric GNRs with urologic instumentation

Vertebral Osteomyelitis: Sources of Infection

• S= Surgery of spine or disc• P= Pulmonary infection with bacteremia• I= IVDU• N= Nephrologic disease• E= Endocarditis• D= Dental work• I= Infected catheter• S= Soft tissue infection

Vertebral Osteomyelitis: Symptoms

• Insidious onset of spinal pain over 3 weeks to 3 months - near universal

• Exam and lab findings:– Local tenderness – near universal– Fevers – 50%– Leukocytosis – 50%– Elevated ESR – 80%

• Prognostic value– Erythema over the involved bones– Motor and sensory deficits in 6-15% of patients

Contiguous Spread Without Vascular Compromise

• Predisposing factors:– Surgical reduction and internal fixation of a fracture– Trauma, open fractures– Prostheses– Chronic soft tissue infections

• Presents ~ 1 month after inoculation of the organisms• Infecting organisms

– Polymicrobial infection common– S. aureus, Gram negative bacilli, anaerobes

• Loss of bone stability, necrosis, soft tissue damage common

Contiguous Spread With Vascular Compromise

• DM and PVD• Most common site = small bones of feet• Combined risk factors

– Peripheral neuropathy, lack of sensation = repetitive microtrauma

– Inadequate tissue perfusion = poor wound healing

• Polymicrobial– Coag (+/-) Staph, Strep spp, Enterococcus, GNR,

anaerobes

Contiguous Spread With Vascular Compromise

• May present later due to lack of patient complaints– Concurrent peripheral neuropathy– Fever and systemic toxicity are frequently absent

• Physical exam– Diminished dorsalis pedis and posterior tibial pulses– Poor capillary refill– Decreases sensation

• DX– Exposed bone before or after debridement of ulcer bed– Probe to bone

• Resection or amputation almost always needed

Contiguous focus osteomyelitis in a 40-year-old male patient with diabetes mellitus. Bony destruction is visible around the proximal and distal phalanges of the first toe.

Osteomyelitis: Special Situations

• Hemodialysis patients– Most are hematogenous in origin– S. aureus and S. epidermidis– Ribs and thoracic vertebrae most common sites

• Sickle cell patients– Salmonella spp, Proteus, S. aureus– Difficult to differentiate thrombotic marrow crisis

from osteomyelitis– May have multiple sites of bone infection

Osteomyelitis: Special Situations

• IV drug users– Common sites include vertebrae, SI, pubis,

clavicles/SC– Pseudomonas, S. aureus, S. epidermidis, GNR, Candida

spp.– Clinical signs and symptoms may be subtle

• Brodie’s Abscess– Subacute osteomyelitis of – classically – distal tibia– Chronic dull pain– Mimics tumor, etc

Diagnosis

• Difficult to diagnose noninvasively– Symptoms, exam, labs, and imaging studies can help

to establish an index of suspicion• Definitive diagnosis = bacterial isolation via bone

BX with compatible histologic findings• Lack of good prospective studies using this

standard– Newman et al. DM foot ulcers and osteo

• Osteo DX in 9/41 (22%) pts without bone CX• Osteo DX in 28/41 (68%) by bone BX

Diagnosis

• Factors affecting the accuracy of current noninvasive tests:– Intensity of the inflammation– Chronicity of the infection– Site of the infection– Vascularity– Presence or absence of a foreign body– Presence or absence of associated pathology

Diagnosis: Bone Biopsy

• Gold standard– Isolation of pathogen via sterile bone BX– Compatible histopathologic features

• Necrotic bone with inflammatory exudate

• CX (+) in up to 87% of cases– ABX can be held 48-72 hours prior to increase yield

• When is bone BX not needed?– Positive blood CX and consistent radiographic studies– Further compromise site with vascular compromise

Diagnosis: Bone Biopsy

• Non invasive CX techniques

• Swab CX correlate poorly with bone BX – 20%

• Sinus tract CX generally not useful – 44% of sinus tract CX contained pathogen on bone

BX– Correlation higher with S. aureus and Salmonella

Diagnosis: Bone Biopsy

• Invasive techniques– Open preferred to percutaneous (PC) needle BX

• Sampling error• Limited sensitivity in post operative and trauma• (-) PC needle BX and high index of suspicion? = open BX

– Percutaneous• ALWAYS thru intact tissues• 2 specimens; CX and path• Always thru uninvolved skin• Fluro guided• Hold ABX

Diagnosis: Plain Films

• Pros– Relatively inexpensive– Readily available– May help make DX– Help in selection and

interpretation of other studies

– Allow exclusion of other conditions

• Cons– Lack sensitivity,

specificity in DX – Lag progress of infection

and healing– Difficult to distinguish

etiology of bony changes– Difficult to tell whether

infection is active or inactive

Diagnosis: Plain Films• Earliest changes

– Sublet soft tissue changes (3-5 days)– Regional osteopenia– Periosteal thickening

• Additional findings– Mixed lucency and sclerosis– Fracture non union, periprosthetic lucency

• Confounding osseous findings– Healing fracture: Charcot joint– Tumors: osteosarcoma, giant cell– Post traumatic changes

Diagnosis: CT Scan• Study of choice when MRI is contraindicated

• Evaluation of areas with focal exam findings but normal plain films

• Order with and without contrast• Accurate in detecting:

– Cortical destruction– Intraosseous gas– Periosteal reaction– Soft tissue extension

Diagnosis: MRI

• Excellent spatial resolution– Helpful in differentiating bone vs. soft tissue changes

• Very sensitive– ABNL marrow edema 3-5 days– High Negatie predictive value

• Osteo effectively ruled out if SXs > 1 week and no MRI changes

• Non specific• May overestimate extent of infection,

underestimate response to TX

Diagnosis: MRI

• Especially useful in vertebral or foot involvementSpine– Delineates soft tissue/epidural involvement– May show cord impingementFoot– Equally specific and more sensitive than bone scan

Diagnosis: Nuclear Modalities

• Types– Three phase bone scan– Gallium scan– Tagged WBC scan

• When to use?– Equal sensitivity to MRI, less specific in acute

osteo– Loses sensitivity in complicated / chronic cases– Not affected by metal hardware

Diagnosis: 3 Phase Bone Scan• Tc-99 bound to phosphorus • Accumulates in areas of increased osteoblastic activity / bone

turnover• Images

– Immediate (blood flow phase)– 15 minute (blood pooling phase)– 4 hour (osseous phase)

• Interpretation– Osteomyelitis: Intense uptake in all 3 phases– Cellulitis: Increased activity in the phase 1 and 2, normal or diffuse

increased activity in phase 3• TRACER UPTAKE IS DEPENDANT ON BLOOD FLOW

– Limits sensitivity in DM, chronic osteo

Diagnosis: 3 Phase Bone Scan

• Pros– Excellent sensitivity and

specificity (95%) in 2 to 3 days IF PLAIN FILMS NL

– Considered the test of choice if plain films normal

• Cons– Decreased sensitivity in

chronic osteo– Multiple possible false

positives: post-injury post-surgery diabetic feet septic arthritis cancer healed osteomyelitis Paget’s disease

Diagnosis: Other Tests• Indium labeled leukocyte scans

– Accumulate at site of infection – NOT SPECIFIC FOR BONE

• Gallium and dual tracer scans– Use gallium-67 alone or with Tc-99– Ga-67 has affinity for acute phase reactants– May be more specific than triple phase study– Scan typically performed 24 hours after injection

• Ultrasound– Fluid collections next to the bone, periosteal elevation and thickening– May improve the yield from needle biopsies

Imaging: Diagnosis Overview

Acute Plain films + Done if + Blood Cx_

MRI or Bone Scan

Complicated Spine or Diabetic Foot?

Yes MRI

No

Hardware? MRI (or CT)NoYes

Bone Scan

Osteomyelitis: Treatment

• Frequently requires surgical and antimicrobial TX– Sugery for drainage, debridement, dead space

management, removal of hardware– Specific antimicrobial coverage

• Bone infection may recur years after apparently successful treatment

• Predisposing factors to recurrence– Trauma to the area– Suppression of the host’s immune response

Treatment: Antibiotic Selection

• Tailored to culture and sensitivity findings• Broad spectrum if CX not obtainable

Treatment: Duration • Int J Infect Dis 2005 9(3):127-38 . 93 clinical trials

from 1968-2000. Available literature on the treatment of osteomyelitis is inadequate to determine the best agent(s), route, or duration of therapy.

• Infect Dis Clin N Am 19(2005): 765-786– Duration: 4-6 weeks

• Animal models• Obervations re: bone revascularization (4 wks)• Lack of improved outcomes with courses of ABX > 6 wks (some up to 6

months)

Treatment: Route• Infect Dis Clin N Am 19(2005): 765-786

– Oral quinolone regimens can be started as soon as tolerated

– “Before changing to a nonquinolone oral regimen, the authors usually treat with 2 weeks of parenteral ABX.”

– “The decision to use oral vs. parenteral ABX should be based on microorganism sensitivity results, pt compliance, infectious disease consultation, and surgeon experience.”

• ID pager: 782-1663– Ask for Josh

Treatment: Additional Considerations

• Serial measurments of ESR and CRP can be useful– Add’l clinical / radiographic eval if ABNL at end of

TX• Suppressive TX warrented if infected

hardware must be retained• Shorter ABX regimens with full resection

(amputation) • ID pager: 782-1663

Questions?

Hyperbaric Oxygen Therapy

• Chronic osteomyelitis: HBO MAY be useful– Appropriate surgery and antibiotics also needed

• Increases intramedullary O2 tension more efficient phagocyte killing vs Staph aureus

• Potentiates the effect of tobramycin vs Pseudomonas• Promotes wound healing

Treatment: Acute Hematogenous Osteomyelitis

Children• Identify pathogen• Antibiotic therapy• 2 weeks of parenteral abx

before changing to oral antibiotics

• 4-6 weeks total • Avoid quinolones

Adults• Identify pathogen• Debridement surgery-

especially if no response to abx in 48hrs

• 4-6 weeks of parenteral abx

Osteomyelitis: Treatment• Intravenous Antibiotics and Bone Penetration with Staph

aureus infection

Clindamycin 98.3%Vancomycin 14.5%Nafcillin 9.6%Tobramycin 9.5%Cefazolin 5.7-6.1%Cephalothin 3.7%

• Significance of antibiotic concentrations is unclear

Treatment: Hematogenous Osteomyelitis

• Empiric regimen for adults

1. Nafcillin 2g IV q 4 hr2. Ceftriaxone 2g IV q 24 hr3. Vancomycin 1g IV q 12 hr and

Ciprofloxacin 400mg IV q 12 hr

Note: Regimen slightly different if on hemodialysis, IV drug abuser, sickle cell patient

Recommendations per ePocrates

Treatment: Vertebral Osteomyelitis

• Biopsy Debride Antibiotics • Open surgery not usually necessary

– Only needed for paravertebral or epidural abscesses, failure of abx, or instability

– Spontaneous bony fusion occurs in 1 to 12 months after abx

• Closely monitor neurologic status• Bed rest vs ambulation plus stabilization

Treatment: Vertebral Osteomyelitis

• Empiric regimen for adults

1. Nafcillin 2g IV q 4 hr and Ciprofloxacin 400mg IV q 12 hr2. Vancomycin 1g IV q 12 hr and

anti-pseudomonal beta-lactam or fluoroquinolone

Recommendations per ePocrates

Treatment: Contiguous Focus Osteomyelitis

• Primary problem is infected, necrotic bone• Must remove the nidus to adequately tx

– Includes removal of hardware– Antibiotic beads may be helpful

• Revascularization of bone after debridement takes approximately 3-4 weeks

• Antibiotics should be given for 4-6 weeks after the last major debridement surgery

Antibiotic Recommendations:Post-amputation

Surgical Procedure Duration1. Surgical transection of 4 wks

infected bone2. Excision of infected bone 2 wks3. Amputation proximal to 1-3 days

the infection

Contiguous Focus Osteomyelitis: With Vascular Disease

• Difficult to treat• Often beyond simple salvage by the time of

presentation• Determination of the vascular status of the

infected tissue is crucial• Several management options

Contiguous Focus Osteomyelitis: With Vascular Disease

• Management options– Suppressive antibiotic therapy– Local debridement surgery– Amputation– Adjunctive hyperbaric oxygen therapy