Osteomyelitis

Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus, but a variety of organisms have been linked to osteomyelitis. The majority of patients present with pain, redness, and swelling of the affected site, and may have associated symptoms such as fever and chills. Laboratory values will demonstrate elevated WBC, CRP, and erythrocyte sedimentation rate (ESR) in most cases. The most sensitive and specific imaging modality to diagnose osteomyelitis is MRI. Management may require long-term antibiotics and potential surgical debridement.

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Epidemiology and Etiology

Epidemiology

  • Overall incidence is unknown.
    • May account for approximately 50,000 cases annually in the United States
    • Higher incidence in developing countries
  • Males > females
  • Non-hematogenous osteomyelitis is more common in adults.
  • Hematogenous osteomyelitis is more common in children.
    • Long bone osteomyelitis is the most common subtype in children.
    • Vertebral osteomyelitis is the most common subtype in adults.

Etiology and classification

Osteomyelitis is classified based on the route of infection.

Non-hematogenous osteomyelitis (80% of cases):

  • Direct inoculation of bacteria due to: 
    • Surgery
    • Prosthetic devices
    • Trauma
    • Hardware for fracture fixation
    • Soft tissue infection
  • Polymicrobial:
    • Staphylococcus aureus (present in > 50% of cases)
    • S. epidermidis
    • Streptococcus
    • Gram-negative bacteria
    • Anaerobic bacteria

Hematogenous osteomyelitis (20% of cases):

  • Bacteria spread via blood supply from the primary site of infection.
  • Monomicrobial: 
    • S. aureus (most common)
    • Streptococcus
    • Enteric gram-negative bacteria
    • Pseudomonas aeruginosa
    • Serratia
    • Salmonella
    • Mycobacterium tuberculosis
    • Neisseria gonorrhoeae
    • Kingella
    • Bartonella henselae
    • Candida
    • Histoplasmosis
    • Blastomycosis
    • Coccidioidomycosis

Risk factors

  • Non-hematogenous: 
    • Trauma
    • Pressure ulcers
    • Foreign body (prosthetics)
    • Diabetes
    • Peripheral vascular disease 
    • Peripheral neuropathy
  • Hematogenous:
    • Sickle cell anemia
    • Diabetes
    • IV drug use
    • Indwelling catheters
    • Immunodeficiency
    • Endocarditis
Table: Common causes of osteomyelitis based on patients’ underlying risk factors
Risk factors Infectious agents
No specific risk factor S. aureus
Prosthetic joint replacement
  • S. aureus
  • S. epidermidis (creates biofilms on prosthetics)
Sickle cell anemia
  • S. aureus
  • Salmonella
Chronic granulomatous disease
  • Serratia
  • Aspergillus
Vertebral osteomyelitis (Pott’s disease)
  • M. tuberculosis
  • S. aureus
Sexually active, no other risk factors N. gonorrhoeae (more likely to cause septic arthritis than osteomyelitis)
Cat or dog bite Pasteurella multocida
IV drug use or immunocompromised
  • P. aeruginosa
  • S. aureus
  • Candida

Pathophysiology

Osteomyelitis is an infection of the bone that results from hematogenous or non-hematogenous spread of infectious organisms.

  • Since bone is usually resistant to infection, the following is usually required:
    • A large inoculum of organisms
    • Bone damage
    • Foreign material
  • The pathogenesis is poorly understood, but appears to be affected by several factors:
    • Host immune status
    • Underlying disease
    • Virulence of the organisms:
      • Adherence
      • Defense mechanisms
      • Proteolytic activity
    • Vascularity and location of bone (e.g., the metaphysis of bone is commonly affected in hematogenous spread due to the rich vascular supply of the growth plates)
  • Timeline of infection:
    • Acute osteomyelitis evolves over days or weeks.
    • Chronic osteomyelitis persists over months to years and causes:
      • Bone ischemia and necrosis
      • Bone loss
      • Sinus tract formation

Clinical Presentation

Acute osteomyelitis

  • Onset may be gradual.
  • Signs and symptoms:
    • Fever and chills
    • Localized swelling
    • Warmth
    • Erythema
    • Dull pain

Chronic osteomyelitis

  • Similar to acute osteomyelitis
  • Intermittent bone pain
  • Draining sinus tract (pathognomonic)
  • Fever and chills are less common.

Physical exam

  • Check for tenderness to palpation over the bone.
  • Assess for a nidus of infection:
    • Wound healing
    • High likelihood of osteomyelitis if it is possible to probe a chronic ulcer to the bone with a sterile tool
  • Check sensory function.
  • Evaluate for diminished pulses.

Subtypes

Vertebral osteomyelitis:

  • Most common subtype of hematogenous osteomyelitis in adults
  • The lumbar spine is most commonly affected.
  • Slow progression of symptoms:
    • Localized back pain: 
      • Radiation to the legs, abdomen, or groin
      • Worsened with activity and at night
    • Motor and sensory deficits with severe progression

Sternoclavicular and pelvic osteomyelitis:

  • Most frequent in IV drug users
  • Sternoclavicular joint:
    • Anterior chest wall swelling, pain, and tenderness
    • May mimic a soft tissue abscess
  • Pelvic osteomyelitis:
    • Changes in gait or inability to bear weight
    • Hip or buttock pain

Long bone osteomyelitis:

  • Least common subtype in adults, but most common in children
  • Can present similar to septic arthritis of a joint
  • Weight bearing on affected long bones may be difficult.

Diagnosis

Laboratory evaluation

  • The following tests support the diagnosis of osteomyelitis:
    • ↑ WBC
    • ↑ Erythrocyte sedimentation rate (ESR)
    • ↑ CRP:
      • Correlates with clinical response to therapy
      • Can be used for monitoring during treatment
  • The following cultures provide necessary identification and sensitivity data for the causative organism:
    • Blood cultures:
      • Positive in 50% of cases
      • Obtain prior to initiating antibiotics, if possible.
    • Tissue culture:
      • Should also be obtained prior to antibiotics, if possible
      • Bone biopsy is the best way to identify the etiology.
      • Wound or abscess cultures are not reliable.

Imaging

  • X-rays:
    • 1st-line imaging modality
    • May not show changes in first 2 weeks of disease
    • A normal X-ray does not rule out osteomyelitis.
    • Rules out metastasis or fractures
    • Findings:
      • Soft tissue swelling
      • Regional osteopenia
      • Periosteal reaction
      • Cortical thickening
      • Peripheral sclerosis
      • Bony destruction
  • MRI:
    • Most sensitive and specific modality for osteomyelitis
    • Detects infection within 3–5 days of onset
    • Use is limited if surgical hardware is present.
    • Findings:
      • Bone marrow edema is the earliest feature.
      • Cortical destruction
      • Soft tissue inflammation
    • Contrast enhancement helps distinguish abscess margins and adjacent periosteum or soft tissue involvement.
  • 3-phase bone scan:
    • Utilizes a radionuclide tracer, which accumulates in areas of osteoblast activity
    • 3 phases: 
      • Blood flow
      • Blood pool
      • Osseous
    • Significant uptake in all 3 phases in osteomyelitis
  • Tagged WBC scan:
    • Blood is drawn from the patient, and autologous WBCs are labeled with a radionuclide tracer.
    • The tagged cells are then injected back into the patient, and the scan is performed.
    • Tagged WBCs accumulate at the site of infection.
    • Best used in distal extremities
    • Can be falsely positive if other inflammatory conditions are present in the area (e.g., fracture)

Management

Antibiotic therapy

  • Options:
    • Initial empiric therapy:
      • Vancomycin
      • 3rd- or 4th-generation cephalosporin
    • If cultures grow MSSA: 
      • 1st-generation cephalosporins
      • Nafcillin or oxacillin
    • Coverage for MRSA: 
      • Clindamycin
      • Vancomycin
      • Daptomycin
  • May be sufficient in select patients with: 
    • Uncomplicated disease, particularly in children
    • Osteomyelitis of a diabetic foot
    • No underlying hardware or prosthetics

Surgical debridement

  • Often required if osteomyelitis is associated with:
    • Necrotic, purulent wound
    • Infected fluid collections
    • Injured or dead bone
    • Hardware/prosthetics
  • Removal of necrotic and diseased bone:
    • Culture of the wound and bone should be obtained during debridement to narrow antibiotic therapy.
    • Can allow placement of local antimicrobials
  • Hardware removal is often required.

Duration of treatment

  • Length of treatment varies greatly and is influenced by: 
    • Presence or absence of hardware
    • Options for debridement and ability to remove all infected bone
  • Most treatment regimens average 6 weeks.
  • Long-term oral suppressive therapy should be considered for: 
    • Individuals with retained hardware
    • Necrotic bone/tissue that is not able to be debrided
  • Duration may be guided by CRP levels, but is often clinically determined by the resolution of symptoms.

Differential Diagnosis

  • Leukemia: the unregulated proliferation of WBCs that causes the lymph nodes and spleen to enlarge as well as bone marrow failure and anemia. Osteomyelitis and leukemia may present with similar constitutional symptoms, such as night sweats, fever, and bone pain (especially in children). Cross-sectional imaging, peripheral blood smear, and CBC with markedly increased WBC will provide the diagnosis. Management includes chemotherapy.
  • Cancer metastasis: cancers that metastasize to bone include those of the prostate, breast, kidney, thyroid, and lung. The presentation may be similar to osteomyelitis, with long bone pain or back pain. However, constitutional symptoms are rarely seen. On imaging, kidney, thyroid, and lung cancer can appear lytic. Biopsy is the most definitive way to distinguish metastasis from osteomyelitis. Management depends on the primary cancer type.
  • Charcot arthropathy: results from the combination of mechanical and vascular consequences of diabetic peripheral neuropathy. This process triggers a local inflammatory response that causes pain, swelling, and erythema of the affected joint. Patients can also develop skin wounds from their neuropathy and progress to secondary osteomyelitis. X-ray images will confirm the diagnosis. Management includes joint stabilization.
  • Chronic recurrent multifocal osteomyelitis: a sterile inflammatory disorder seen in children that can cause bone damage if not treated. The pathology is poorly understood, but is presumed to be related to osteoclast dysfunction. Children may present with episodic or chronic pain to 1 or multiple areas. The diagnosis is based on imaging. Laboratory values will be normal, unlike in osteomyelitis. Primary treatment involves NSAID therapy. Immunosuppression may be needed if primary treatment fails.
  • Septic arthritis: an infection of the joint that can be caused by bacteria or other microorganisms. Patients present with an acutely swollen, warm joint with limited range of motion. Constitutional symptoms are present in some patients. Diagnosis is made by synovial fluid analysis and culture. Unlike osteomyelitis, there are rarely bony changes on imaging. Management involves drainage, debridement, and antibiotic therapy.

References

  1. Momodu, I. I., Savaliya, V. (2021). Osteomyelitis. StatPearls. Retrieved March 3, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK532250/
  2. Lalani, T., Schmitt, S. K. (2021). Nonvertebral osteomyelitis in adults: clinical manifestations and diagnosis. In Baron, E. L. (Ed.), UpToDate. Retrieved March 3, 2021, from https://www.uptodate.com/contents/nonvertebral-osteomyelitis-in-adults-clinical-manifestations-and-diagnosis
  3. Sopirala, M. M. (2020). Pathogenesis of osteomyelitis. In Baron, E. L. (Ed.), UpToDate. Retrieved March 3, 2021, from, https://www.uptodate.com/contents/pathogenesis-of-osteomyelitis
  4. Osmon, D. R., Tande, A. J. (2021). Nonvertebral osteomyelitis in adults: treatment. In Baron, E. L. (Ed.), UpToDate. Retrieved March 3, 2021, from https://www.uptodate.com/contents/osteomyelitis-in-adults-treatment
  5. Spritzer, C. E. (2020). Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis. In Baron, E. L. (Ed.), UpToDate. Retrieved March 3, 2021, from https://www.uptodate.com/contents/approach-to-imaging-modalities-in-the-setting-of-suspected-nonvertebral-osteomyelitis
  6. Hordon, L. D. (2020). Diabetic neuropathic arthropathy. In Romain, P. L. (Ed.), UpToDate. Retrieved March 3, 2021, from https://www.uptodate.com/contents/diabetic-neuropathic-arthropathy
  7. Schmitt, S. (2020). Osteomyelitis. StatPearls. Retrieved March 4, 2021, from https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/infections-of-joints-and-bones/osteomyelitis
  8. Kishner, S., Hart, E. K., Nixon, G. C., and Laborde, J. M. (2020). Osteomyelitis. In Poduval, M. (Ed.), Medscape. Retrieved March 4, 2021, from https://emedicine.medscape.com/article/1348767-overview

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