Osteomyelitis

Osteomyelitis is an infection of the bone acquired hematogenously or by contiguous site infection. In children, hematogenous spread is more common, and the long bones are more often infected. In adults, hematogenously seeded osteomyelitis is seen; however, extension from contiguous sites is more likely. Diabetic foot ulcers and pressure sores are common predisposing conditions.

Diagnosis

Indications for Testing

Chronic, nonhealing ulcer that can be probed to the bone (eg, diabetic foot ulcer, decubitus ulcer in immobilized patient)
Localized bone pain with signs and/or symptoms of infection
Back pain or neck pain with
- Fever
- Elevated C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR)
- Blood-stream infection or infective endocarditis
- Recent Staphylococcus aureus bacteremia
New neurological symptoms with or without back pain or neck pain

Laboratory Testing

CBC
- May be normal or show leukocytosis or left shift
- Leukocyte count may be normal in chronic or indolent osteomyelitis
- Normocytic normochromic anemia may be present if infection is chronic (anemia of chronic inflammation)
CRP
- Preferred test to detect acute inflammation (Choosing Wisely, American Society for Clinical Pathology, 2016)
- Emerging as preferred marker for diagnosis and monitoring of osteomyelitis
- Frequently elevated but not specific
- Normal ESR and CRP essentially rule out osteomyelitis
- Specific types
  - Vertebral osteomyelitis – use CRP in conjunction with ESR in all patients with clinical signs (Infectious Diseases Society of America [IDSA], 2015)
  - Diabetic foot osteomyelitis – use CRP with ESR in conjunction with white blood cell (WBC) count to assess severity of infection of ulcer (IDSA, 2012)
ESR (sed rate, Westergren sedimentation rate) – order if CRP not available
- Marker of inflammation – increases and decreases more slowly than CRP
- Diabetic foot osteomyelitis – ulcer depth >3 mm and ESR >60 mm/hr assist in differentiation of cellulitis from osteomyelitis (IDSA, 2012)
Routine blood culture
- Collect prior to antibiotic administration in all suspected cases
- ≥2 sets of cultures (aerobic and anaerobic) should be obtained from different draws (IDSA, 2015)
- Positive cultures may preclude need for bone biopsy
- Positive in up to half of cases
Tissue culture
- Superficial culture not useful
- Bone sample necessary unless organism identified in blood
- Bone or deep tissue obtained at debridement, or imaging-guided or surgical biopsy/aspirate
Procalcitonin
- Use in conjunction with other inflammatory markers (acute phase reactant)
- Elevated in severe bacterial disease (eg, sepsis)
- Being evaluated as assessment of osteomyelitis disease severity
Other organism testing for vertebral osteomyelitis (rare organisms)
- Test if risk factors or epidemiology appropriate or after no growth of bacterial cultures
- Blood cultures and serologic tests for Brucella recommended for patients with vertebral osteomyelitis in endemic areas
- Obtain fungal cultures if patient is at risk for fungal vertebral osteomyelitis due to risk factors or epidemiologic factors
- Purified protein derivative (PPD) or interferon – gamma release assay for mycobacterium tuberculosis (TB) for at-risk patients
Polymerase chain reaction (PCR)
- Not widely available; may be useful if all cultures are negative
- Most useful for Bartonella henselae and Kingella kingae

Imaging Studies

Criteria for diagnosis
- American College of Radiology (ACR) Appropriateness Criteria outline recommendations for imaging for suspected osteomyelitis in diabetic foot ulcers
Imaging modalities for osteomyelitis
- Plain x-ray films – may not demonstrate presence of osteomyelitis until 10-14 days after infection is established
  - Negative film does not rule out diagnosis
  - Evidence for osteomyelitis on film – periosteal lifting or lytic lesions
- Magnetic resonance imaging (MRI) – indicated after x-ray or in combination to identify extent of disease
- Labeled leukocyte bone scan – indicated in absence of MRI
- Computerized tomography (CT) scan – not as sensitive as MRI; not useful if metal is near the infection

Differential Diagnosis

Arthritis
- Septic
- Degenerative
- Crystalline
- Reactive
Juvenile rheumatoid arthritis
Neuropathic disease
Metastatic bone disease
Paget disease

Monitoring

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
- Recommended after 4 weeks of antimicrobial therapy for vertebral osteomyelitis to evaluate response (IDSA, 2015)
- CRP likely as effective alone

Background

Epidemiology

Incidence (Kremers, 2015)
- 21.8/100,000 person-years (U.S. adults)
- 8.8/100,000 (U.S. children)
Sex – M>F
- Children – more than 50% occur in children <5 years
- Adults – incidence increases with age

Risk Factors

Children
- Blunt trauma
- Postoperative
Adults
- Peripheral vascular disease
- Diabetes mellitus
- Renal or hepatic failure
- Immunosuppression
- Malignancy
- Neuropathy
- Intravenous drug use
- Trauma
- Surgery – particularly prosthetic implants

Organisms

Most common organism
- Staphylococcus aureus
Diabetes mellitus, peripheral vascular disease
- Streptococcus spp
- Coagulase-positive and -negative Staphylococcus spp
- Enterococcus spp
- Anaerobic spp, often polymicrobial
Intravenous drug use
- Pseudomonas aeruginosa
Infants and children
- Staphylococcus spp
- S. pneumoniae
- Group A Streptococcus (especially post chickenpox)
- Kingella kingae
Neonates
- Group B Streptococcus
- Gram-negative species
Hemoglobinopathies
- Salmonella spp
Uncommon pathogens
- Fungal and mycobacterial pathogens