What is the pathophysiology and treatment of spondylodiscitis?

Pathophysiology and Treatment of Spondylodiscitis

Pathophysiology

Spondylodiscitis is an infection of the vertebral body (spondylitis) and adjacent intervertebral disc (discitis), most commonly spread via hematogenous seeding from bacteremia, with the avascular adult disc becoming infected following initial septic embolization to the vertebral endplate. 1

Mechanism of Infection

• Hematogenous spread is the primary route of infection in adults, where bacteria from bloodstream infections seed the highly vascular vertebral endplates 1, 2
• The adult intervertebral disc is avascular, so infection typically begins at the vertebral endplate and then extends into the adjacent disc space 1
• Bacteremia and endocarditis are among the most significant risk factors for developing spondylodiscitis 1
• Less commonly, infection occurs through direct extension from adjacent soft tissue infections or direct inoculation during spinal procedures or penetrating trauma 1

Pattern of Involvement

• Single-level involvement occurs in 65% of patients 1, 3
• Contiguous multilevel infection occurs in approximately 20% of cases 1, 3
• Non-contiguous multilevel infection occurs in about 10% of patients 1, 3
• Infection can extend to posterior bony elements, pre- and paravertebral soft tissues, and the epidural space 1

Microbiology

• Staphylococcus aureus (including MRSA) is the most common pathogen, accounting for up to 80% of pyogenic cases 4, 5
• Coagulase-negative staphylococci are the second most common bacterial cause 6
• Gram-negative bacilli and anaerobes account for remaining bacterial cases 6
• Tuberculosis, Brucella, and fungal pathogens should be considered in specific epidemiological contexts 7, 5

Risk Factors

• Intravenous drug use is a major risk factor 2
• Immunocompromised states including HIV, diabetes, and chronic kidney disease on hemodialysis 2, 8, 5
• Intravascular devices and bacteremia from any source 8
• Advanced age and frailty increase susceptibility 2, 4

---

Treatment Approach

Diagnostic Strategy Before Treatment

In hemodynamically stable patients without neurological compromise, withhold empirical antibiotics until microbiological diagnosis is established through biopsy or blood cultures. 7

• Blood cultures should be obtained for aerobic and anaerobic bacteria, with positivity rates of 53-54% in pyogenic and brucellar cases 5
• Image-guided or surgical biopsy has higher diagnostic yield than blood cultures and should be pursued when feasible 3, 7
• 16S rRNA PCR on tissue samples provides superior pathogen detection compared to standard microbiological culture 4
• If initial biopsy is negative, perform second biopsy with specific cultures for mycobacteria, Brucella, fungi, and anaerobes 7

Empirical Antibiotic Therapy

Empirical antibiotics should only be initiated in patients with hemodynamic instability, sepsis, progressive neurological deficits, or spinal cord compression. 7

Recommended Empirical Regimen

• Vancomycin 15-20 mg/kg IV every 12 hours PLUS one of the following 3, 7, 6:
  • Cefepime 2 g IV every 8-12 hours, OR
  • Meropenem 1 g IV every 8 hours, OR
  • Ertapenem 1 g IV every 24 hours, OR
  • Ceftriaxone 2 g IV every 24 hours PLUS metronidazole 500 mg IV every 8 hours

This regimen provides coverage for MRSA, gram-negative bacilli, and anaerobes 6

Duration of Antibiotic Treatment

Administer initial parenteral therapy for 2-4 weeks, followed by oral antibiotics to complete 6-12 weeks of total treatment. 3, 7, 6

• Six weeks of total treatment is non-inferior to 12 weeks, with clinical cure rates of 90.9% in both groups 3, 6
• Switch to oral therapy can occur after median 2.7 weeks of IV therapy once CRP decreases and significant abscesses are drained 6
• Oral agents with excellent bioavailability include fluoroquinolones, linezolid, and metronidazole 6
• Avoid oral β-lactams for initial treatment due to poor bioavailability 6

Targeted Therapy Adjustments

• Modify empirical therapy once culture and sensitivity results are available 6
• For Candida spondylodiscitis, use liposomal or lipid complex amphotericin B followed by fluconazole, or fluconazole monotherapy if susceptible 1
• Surgical debridement is indicated for instability or large abscesses in fungal cases 1

Surgical Indications

Surgery is indicated for neurological deficits with spinal cord compression, progressive spinal deformity, failure of conservative therapy with insufficient pain relief, unreliable pathogen identification requiring debridement for sampling, or spinal instability. 3, 2, 4

Surgical Approach Considerations

• Anterior approach allows for disc and bone debridement 9
• Posterior approach is indicated when posterior elements are involved or epidural abscess is present 9
• Minimally invasive and endoscopic techniques reduce blood loss, surgical time, and hospital stay 2, 9
• Titanium and PEEK implants as well as autograft and allograft are safe in pyogenic spondylodiscitis 2
• Some studies recommend stabilization without aggressive debridement in frail patients 2

Monitoring and Follow-up

Monitor ESR and CRP as primary means to evaluate treatment response, with significant reduction expected in the first few weeks. 3, 4

• Daily monitoring of temperature, neurological status, and pain while awaiting diagnostic results 7
• CRP and ESR should be checked after 4 weeks of treatment 7
• MRI with and without contrast is the primary imaging modality for follow-up, with sensitivity 96%, specificity 94%, and accuracy 92% 1, 3
• [18F]FDG PET/CT is preferred for detection within the first 14 days of symptom onset 3
• CT is useful for evaluating complications in patients with spinal hardware or when MRI is contraindicated 6

Treatment Outcomes and Complications

• Mortality rates range up to 20% in pyogenic spondylodiscitis 2
• Treatment failure rates vary between 10-30%, with risk factors including multidisc disease, epidural abscess, S. aureus infection, advanced age, and significant comorbidities 6
• Prolonged antibiotic treatment is associated with higher intolerance (50% vs 10%) and increased risk of Clostridioides difficile colitis 6
• Neurological deficits are present in up to 50% of patients at presentation 4

Special Epidemiological Considerations

• Brucella infection should be considered in patients consuming unpasteurized dairy products 7
• Tuberculosis should be considered in patients with unstable living conditions, malnutrition, and exposure risk 7
• Fungal infections should be considered in immunosuppressed patients, diabetics, or IV drug users 7
• Night sweats are more prevalent in brucellar spondylodiscitis, while weight loss is less frequent in pyogenic cases 5