Vertebral Osteomyelitis

Vertebral osteomyelitis (spondylodiscitis) is an infection of the vertebral bodies and the adjacent intervertebral disc, which may spread to the epidural space and paraspinal tissues. In adults it is mostly pyogenic and haematogenous, and it is a serious cause of back pain because delayed diagnosis leads to neurological injury and spinal deformity.

The incidence is about 2 to 7 cases in 100 000 people each year and rising, with a peak at 50 to 70 years and a male predominance (about 2 to 1). Risk factors are diabetes, injection drug use, haemodialysis, endocarditis, immunosuppression, indwelling catheters, and recent spinal surgery or injection. The lumbar spine is affected in about 58%, thoracic 30% and cervical 11%.

Staphylococcus aureus causes 30 to 55%, then streptococci, enterococci and Gram negative bacilli (Escherichia coli from the urinary tract, Pseudomonas in injection drug use), Cutibacterium acnes with implants, Salmonella in sickle cell disease, Brucella, Mycobacterium tuberculosis, and fungi (Candida, Aspergillus) in immunosuppressed patients. Diagnosis is delayed by 2 to 6 months on average. Mortality is 2 to 20%, neurological deficit occurs in 10 to 30%, and about a third have chronic pain or deformity.

Pathophysiology.

Bacteria seed the subchondral vertebral end plate through segmental arteries or the valveless venous plexus (Batson plexus), then spread through the end plate to the avascular adult disc. Direct inoculation follows surgery, injection or trauma, and contiguous spread follows adjacent infection. End plate destruction, disc narrowing, vertebral collapse, kyphosis, epidural abscess and psoas abscess follow; biofilm forms on implants.

Insidious axial back or neck pain, worse at night and not relieved by rest, with local spinal tenderness and muscle spasm. Fever is present in only 35 to 50%. Other features: weight loss, sweating, radicular pain, and neurological deficit (weakness, sensory loss, sphincter dysfunction). Sepsis may be the first presentation.

Examine the spine (percussion tenderness), full neurological state (power, sensation, reflexes, anal tone), the skin (injection sites), the heart (new murmur), the teeth, urinary tract, and any implants or devices.

• Inflammatory markers: ESR above 20 mm/hour in over 90% (often over 50) and raised CRP, which is useful for monitoring; white cell count may be normal.
• Blood cultures (2 to 3 sets) before antibiotics: positive in 30 to 70%.
• MRI of the whole spine with gadolinium (sensitivity over 90%): end plate erosion, disc hyperintensity on T2 signal, paraspinal and epidural collections, cord compression, and skip lesions (4 to 10%). Radiographs are normal for 2 to 8 weeks.
• CT shows bone destruction and allows biopsy; PET-CT or a bone scan if MRI is contraindicated.
• Image directed or open biopsy for culture, histology and molecular tests when blood cultures are negative (yield 50 to 80%); culture for mycobacteria and fungi; Brucella serology in endemic areas; interferon gamma release assay or nucleic acid tests for tuberculosis.
• Echocardiography (transthoracic then transoesophageal) for Staphylococcus aureus or enterococcal bacteraemia; HIV test, HbA1c, urinalysis and renal function.

Differential diagnosis.

• Degenerative disc disease with Modic type 1 change, and Schmorl node.
• Tuberculous spondylitis and brucellosis.
• Metastasis, myeloma and lymphoma.
• Charcot spine, spondyloarthropathy (Andersson lesion), crystal disease, and vertebral fracture.

The aims are to identify the organism, eradicate infection, relieve pain, protect neurological function and keep spinal stability.

Antimicrobial therapy. When the patient is haemodynamically stable and neurologically intact, withhold antibiotics until the organism is identified (blood cultures, then biopsy). Start immediately for sepsis, neurological deficit, or instability.

• Empirical treatment: vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours (adjust to trough 15 to 20 mg/L and creatinine) with ceftriaxone 2 g intravenously every 24 hours.
• With Pseudomonas risk (injection drug use), use ceftazidime 2 g intravenously every 8 hours instead of ceftriaxone.
• Methicillin susceptible Staphylococcus aureus: flucloxacillin 2 g intravenously every 4 to 6 hours (maximum 12 g daily) or cefazolin 2 g intravenously every 8 hours (maximum 6 g daily).
• Methicillin resistant Staphylococcus aureus: vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours (adjust to trough 15 to 20 mg/L and creatinine).
• Alternative for methicillin resistant Staphylococcus aureus: daptomycin 8 to 10 mg/kg intravenously once daily (check creatine kinase weekly; stop statins; avoid in pneumonia).
• Alternative for methicillin resistant Staphylococcus aureus: linezolid 600 mg orally or intravenously every 12 hours (limit to 2 to 4 weeks; monitor blood count weekly; avoid with serotonergic drugs).
• Streptococci: benzylpenicillin 2.4 g intravenously every 4 hours or ceftriaxone 2 g intravenously every 24 hours.
• Enterococcus faecalis: amoxicillin 2 g intravenously every 4 to 6 hours (maximum 12 g daily).
• Gram negative bacilli: ceftriaxone 2 g intravenously every 24 hours, or ciprofloxacin 750 mg orally every 12 hours (400 mg intravenously every 8 to 12 hours) if susceptible.
• Pseudomonas: ceftazidime 2 g intravenously every 8 hours with ciprofloxacin.
• Extended spectrum beta lactamase producers: meropenem 1 g intravenously every 8 hours.
• Implant associated staphylococcal infection: add rifampicin 600 mg orally once daily after debridement and clearance of bacteraemia (monitor liver function; interactions with warfarin, direct oral anticoagulants, contraceptives and many drugs).
• Candida: fluconazole 400 to 800 mg orally or intravenously daily, or caspofungin 70 mg loading dose then 50 mg intravenously daily, for 6 to 12 months.
• Brucellosis: doxycycline 100 mg orally twice daily with rifampicin 600 to 900 mg orally once daily for at least 12 weeks, with gentamicin 5 mg/kg intravenously once daily for the first 7 to 14 days.
• Tuberculous spondylitis: rifampicin 10 mg/kg orally daily (maximum 600 mg), isoniazid 5 mg/kg (maximum 300 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg for 2 months, then rifampicin and isoniazid for 7 to 10 months (9 to 12 months in all).
• Tuberculous spondylitis, with pyridoxine 10 to 25 mg daily; monitor liver function and visual acuity.
• Duration and route: 6 weeks for pyogenic infection (extended to 12 weeks for undrained abscess, implants or resistant organisms).
• Oral step down after 1 to 2 weeks of intravenous treatment is as effective in selected patients with well absorbed drugs: ciprofloxacin 750 mg every 12 hours, levofloxacin 750 mg once daily, co-trimoxazole 960 mg every 12 hours, clindamycin 600 mg every 6 to 8 hours (maximum 2.4 g daily), or linezolid.
• Fluoroquinolones: risk of tendon rupture, QT prolongation, aortic aneurysm and central nervous system effects (avoid with corticosteroids and in older adults when alternatives exist).

Surgery (neurological deficit with epidural abscess, spinal instability or progressive deformity, failure of medical therapy, large abscess requiring drainage, or no organism after biopsy). Decompression, debridement and drainage; anterior debridement with strut graft or cage reconstruction; posterior instrumentation (safe in infection after debridement). Antibiotics are withheld before open biopsy only when the patient is stable.

Supportive care.

• Bed rest for pain in the early phase, then mobilisation in a thoracolumbosacral orthosis for comfort and stability.
• Glycaemic control (blood glucose 6 to 10 mmol/L).
• Nutrition.
• Treat the source (endocarditis, urinary infection, skin infection).
• Addiction services and opioid substitution for injection drug use.
• Enoxaparin 40 mg subcutaneously once daily while immobile (20 mg at creatinine clearance under 30 mL/min; hold 12 hours before biopsy or surgery).
• Paracetamol 1 g orally every 6 hours, with oral morphine 5 to 10 mg every 4 hours as needed for severe pain (start 2.5 to 5 mg with age over 75 or eGFR under 30 mL/min/1.73 m2).
• Laxative.

Monitoring. Neurological examination at least daily at first; CRP and ESR weekly (falling CRP signals response); full blood count, creatinine and liver function weekly; vancomycin levels; creatine kinase with daptomycin; echocardiography if bacteraemia. Repeat MRI only for clinical failure, since imaging may look worse despite improvement. Review at 3, 6 and 12 months, with radiographs for kyphosis and fusion.

Referral and escalation. Refer any adult with suspected vertebral infection urgently for MRI of the whole spine, spinal surgical review and infectious disease advice. Emergency referral for sepsis, neurological deficit, or epidural abscess.

Special groups.

• Injection drug users: Pseudomonas and Staphylococcus aureus cover, endocarditis screen, addiction support, and outpatient parenteral therapy only with a safe plan.
• Older adults and patients on haemodialysis: adjust drug doses to renal function; higher mortality.
• Pregnancy: use beta lactams; avoid fluoroquinolones, tetracyclines and aminoglycosides; MRI without gadolinium.
• Diabetes: strict glucose control; screen for foot and urinary infection.
• Post-operative implant infection: debridement with implant retention or exchange, and prolonged therapy with rifampicin.