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Definition

Infection of the bony and soft tissue structures involving the spine is a devastating and potentially fatal condition, which can result spontaneously in response to bacteremia or as a complication of surgery, injury, or procedures. This represents 2% to 7% of all spine infections; however, in the recent decades there has been an increase. The rise may be due to improved imaging technologies, to the growing number of older patients with chronic illnesses, and to the increasing cases of spinal surgery or procedures.1 There are multiple confusing terms that refer to spinal infections, such as discitis, vertebral osteomyelitis, pyogenic spondylitis, septic facet joint, and Pott’s disease. Spondylodiscitis is the correct terminology to describe primary spinal infections, the most common type of spinal infection.2

Etiology

Primary spine infections are hematogenous. The infective organism seeds the vertebral bodies during times of bacteremia. Secondary infections are introduced into the spine via non-hematogenous routes, including trauma, surgery, and injections. Primary discitis in adults is not commonly seen because the disc is avascular. It is seen secondary to vertebral osteomyelitis or is iatrogenic following a discogram, surgery, or inadvertent disc injection during a spinal procedure. In a study of 159 patients treated for spondylodiscitis 35% were secondary infections due to previous open spine surgery, and 65% were primary infections. Primary infections progress more severely and result in significantly higher mortality rate than secondary or postoperative infections (12.5% vs. 1.8%).3

Epidemiology including risk factors and primary prevention

The incidence of spondylodiscitis varies between 1 to 5 cases per 100,000 and increases with age.1

The mean age of diagnosis is 58.3 years old with 60% of patients being men.4 In this meta-analysis of 4173 patients across 50 studies, the most common comorbidities and risk associated with spondylodiscitis are

  • Concurrent infection (35%, 207/834, 14 studies)
  • Cardiovascular diseases (24%, 260/1083, 13 studies)
  • Diabetes (20%, 651/3272, 33 studies)
  • Intravenous drug abuse (15%, 226/1379, 14 studies)
  • Immunosuppression (11%, 274/2429, 20 studies).4 

Pyogenic spondylodiscitis is most commonly caused by Staphylococcus aureus, and secondly by Enterobacteriaceae spp. Escherichia coli is the most common of the gram-negative family.2 Mycobacterium tuberculosis is the most common pathogen to cause spondylodiscitis worldwide.5    

The most common infection risk factors in order of most common to least common are 6

  • Age >65 years – 15/40 (37.5)
  • Prior non-spine infection (in past 1 month) – 12/40 (30.0)
  • Spine surgery (>1 years ago) – 9/40 (22.5)
  • Nonspine malignancy – 9/40 (22.5)
  • Diabetes mellitus – 8/40 (20.0)
  • Current nicotine use 8/40 (20.0)
  • Spine surgery (⩽1 year ago) – 6/40 (15.0)
  • Prior spine infection – 5/40 (12.5)
  • Non-spine surgery (⩽1 year ago) – 5/40 (12.5)
  • Immune suppression or corticosteroid use 5/40 (12.5)
  • Decubitus or other skin ulcer – 5/40 (12.5)
  • Intravenous or other illicit drug use – 3/40 (7.5)
  • Spine fracture / trauma – 1/40 (2.5)
  • Indwelling catheters, intravenous cannulas 1/40 (2.5)
  • Malnutrition

Patho-anatomy/physiology

The vertebral arteries form end arteries on either side of the disc. This grants the infective organism access adjacent to the endplates. The primary site of infection usually involves the two adjacent vertebra and intervening disc .7 In adults, the intervertebral disc is a relatively avascular structure and provides some protection against hematogenous spread of infection to the disc. In patients under age 20, there is residual blood supply to the disc; if infection does spread to the disc, primary discitis occurs. Infection can spread locally into the disc from the adjacent vertebral osteomyelitis. The anatomy reveals that the outer two thirds of the disc is firmly adherent to the vertebral endplate, however, the central portion of the disc may be more loosely adherent and have endplate openings to allow venous drainage which can be a site of pathogen entry.

In the lumbar spine, the Batson Venous Plexus, because of its rich anastomosis with pelvic organs and its network adjacent to the intervertebral disc, is considered the most likely infectious pathway from pelvic and abdominal sources.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

An infective organism causes localized suppuration also known as pus. This cuts off the nutrient supply to the disc, causing rapid deterioration. The intervertebral disc, which is acellular, offers no resistance, and local tissue necrosis ensues. Collapse of the intervertebral disc space is often early. Infection then spreads anteriorly into the prevertebral space and into the psoas muscle, posteriorly into the epidural space causing an epidural abscess and/or meningitis; it can also spread longitudinally into the adjacent disc and vertebra.

Specific secondary or associated conditions and complications

In rare cases, the infection is walled off and becomes chronic because of formation of dead bone or involucrum. This can lead to recurrence of infection. Worsened osseous and discoligamentous destruction and deformity causes spinal deformity and results in increased disability score and reduced quality of life.4 In about 12% of cases, especially with Staphylococcus aureus or Mycobacterial infection, systemic dissemination results in paralysis and death.

The poor vascularization of the disc makes it a nidus for infection, resulting in prolonged antibiotic treatment. This spread of infection can also be exacerbated by a history of osteomyelitis in which bacteremia and suppuration results in increased intraosseous pressure and decreased blood flow.4

Spread of infection into the epidural space, most commonly in the lumbar spine (48%), can cause cord compression and may lead to permanent cord damage if not decompressed within 72 hours.

In extremely rare cases, infection can spread in the subdural space, causing rapid compression of the spinal cord. Once direct involvement of the central nervous system is observed, outcome is poor.1

Essentials of Assessment

History

The onset of spondylodiscitis can be acute, subacute, and insidious, in the order of decreasing severity of presentation. The progressive nature of the insidious type often delays diagnosis due to unclear time of onset, milder symptoms, and fewer symptoms.7 In adults, spondylodiscitis commonly presents as dull back pain. In children, it can present as inability to walk or move and may be mistaken for muscle strain. Cervical spine infections commonly present with a stiff neck. There may be history of minor trauma. About 50% of patients give a history of fever. Patients with infection often complain of nocturnal pain possibly due to a relative decrease in oxygen saturation while asleep. Radicular symptoms suggest epidural involvement. In subacute and chronic cases there may be weight loss, loss of appetite, and malaise.

Physical examination

  • There are no classical clinical signs for spine infections, but a very detailed spine and neurologic evaluation is essential.
  • Tenderness and deformity of the spinous process along with muscle spasm and reduced range of motion is noted.
  • Pseudoparalysis may be noted in children secondary to pain.
  • Pain may be reproduced with vertical pressure on the vertebra and disc (Anvil test).
  • If vertebral collapse occurs, there may be palpable deformity.
  • Positive straight leg raise tests may suggest epidural involvement.
  • Associated abdominal examination might be needed to assess for the presence of psoas abscess.
  • Cardiac examination may be indicated to rule out infective endocarditis.

In a meta-analysis of spondylodiscitis in adult patients, the most common findings at presentation were 4

  • Back pain – 2101/2299 (91%)
  • Fever – 748/2125 (35%)
  • Neurologic deficits – 1009/3422 (29%)

Functional assessment

One needs to assess if the patient can safely ambulate, whether because of pain or weakness. If there is any question of central nervous system involvement, a formal cognitive assessment would be needed.

Laboratory studies

  • Complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and blood cultures x 3 from different sites, including aerobic and anaerobic, especially when febrile.
  • The most common organism responsible for pyogenic infections is Staphylococcus aureus, followed by Escherichia coli.2 Fungal infections are more likely to be seen in immunocompromised individuals and intravenous drug use.
  • Testing for human immunodeficiency virus, syphilis, and tuberculosis are recommended.

Imaging

  • Magnetic resonance imaging (MRI) is the test of choice with a 92% sensitivity and 96% specificity.8 MRI sensitivity can increase to 95.4% when performed using galodinium contrast.9
  • Computed tomography (CT) scan can help look for osteomyelitis, sequestrum, disc space collapse, and prevertebral and psoas abscess.
  • Plain radiographs are a good initial test to evaluate disease progression, but a negative X-ray does not rule out spondylodiscitis.5
    • Technetium Tc 99m scan is typically positive in a few days following onset of symptoms.
  • Indium-111 labeled white blood cell is a good tool for diagnosis of peridural abscess.
  • Gallium citrate Ga 67 scans have been found to have a sensitivity close to 100%, with increased uptake 1 day earlier than for the Technetium Tc 99m scan. Also, gallium is helpful for chronic osteomyelitis.
    • Gallium-citrate positron-emission tomography (PET)/CT can be useful to differentiate between spinal infections and tumors.
  • PET with fluorodeoxyglucose is not affected by implants and is recommended by the Infectious Diseases Society of America (IDSA) only when MRI is contraindicated.10
  • Ultrasound has been used to diagnose discitis in infants.11 Its role is primarily to diagnose and follow-up on psoas and other prevertebral abscesses.

Supplemental assessment tools

CRP has a sensitivity as high as >90%, ESR is positive in 75% of cases, whereas blood cultures are positive only in 50-60% of cases.1,2 Because isolation of the organism will impact treatment, vertebral biopsy is required if the blood cultures are negative. CT or ultrasound-guided biopsy of the lesion is currently the most common and accurate method of securing a histopathologic diagnosis. A combined superimposed MR and CT imaging is recently being reported to help achieve higher detection rate during CT-guided biopsies.2 Open biopsy may also be performed if the patient is being treated surgically.12 Though this is crucial in subacute and chronic cases to rule out a neoplasm, the sensitivity and specificity of CT-guided biopsy or open biopsy is lower than expected, with surgical biopsy and percutaneous biopsy being positive only 58% and 57% of the time, respectively.4

Early predictions of outcomes

Generally, the indicators of poor long-term outcome include the following:

  • Presence of neurologic signs
  • Longer time to diagnosis
  • Hospital-acquired infection
  • Level of spine involvement (cervical > thoracic > thoracolumbar > lumbosacral)

Social role and social support system

Social and home care agencies need to be involved early to prepare for after care and home antibiotic therapy.

Professional issues

Missing this diagnosis can have serious consequences for both the physician and the patient. Misdiagnosis of spinal infections is a frequent cause of malpractice suits. Worse still are the consequences for the patient as paralysis and death may result.

Rehabilitation Management and Treatments

At different disease stages

The Infectious Diseases Society of America (IDSA) guidelines recommend 6-week of parenteral or oral (high bioavailability) antibiotics for the treatment of vertebral osteomyelitis.10 Patients with an undrained abscess and retained hardware with infection might need treatment for as long as 3 months.

In patients with tuberculosis, treatment with a combination of antituberculous agents is recommended for at least 12 months.

Surgical intervention is required for the following:

  • Open biopsy
  • Epidural/paravertebral/psoas abscess
  • Neurologic deficits
  • Catastrophic infections, which are not responding to nonsurgical treatment
  • Infections related to foreign bodies

Delayed surgery might be needed to stabilize the spine, this is particularly true in children where there is a significant risk for kyphoscoliosis.

Emerging/unique interventions

Outcomes are based on rapid diagnosis and treatment. Patients treated with at least 4 weeks of intravenous antibiotics revealed a 12-month survival without relapse of 88%.

Patients with vertebral osteomyelitis followed for a median of 6.5 years revealed complete recovery in 57%, relapse in 14%, and death in 11%.13 About 31% of patients had incomplete disability because of residual motor weakness, severe pain-limiting function, and isolated neurogenic bladder.

If the patient has severe cord compression, the time window for surgical decompression and potential reversal is about 24 to 72 hours. 14

In a meta-analysis of 21 studies, 19 retrospective/prospective cohort and 2 randomized clinical trials, 330 of 11,607 (2.8%) spinal surgery patients that did not receive vancomycin developed surgical site infection (SSI) and 126 of 8,075 patients that received vancomycin developed SSI. With a cumulative risk of 0.55 (95% CI 0.45–0.67, p < 0.0001) and a number needed to treat of 78 patients, it was demonstrated that vancomycin powder reduces the risk of surgical site infection (SSI).15 Spinal SSI required extended rehabilitation and were associated with further complications extending hospital length of stay.16 Another practice is to use antibacterial-coated sutures which are associated with decreased wound infections.17

Another practice was the use of recombinant human bone morphogenetic protein–2 (rhBMP-2) in surgical treatment of spinal infections that required spinal fusion. There is no significant difference in reoperation rate, hospital readmission, or mortality during the first two years between the rhBMP-2 and no-rhBMP-2 groups. However, patients in the rhBMP-2 group consistently incurred lower use of outpatient services and medication refill costs at 1, 3, 6, 12, and 24 months, presumably attributable to the effective increased fusion rates due to rhBMP-2.18

Because of recent emergence of antibiotic-resistant Staphylococcus aureus, some centers are trying combination therapies. Subsequent oral antibiotic therapies after initial intravenous therapy should be determined by the results of cultures, if possible. For example, anti-staphylococcus penicillin or cephalosporin are used for methicillin-sensitive S. aureus and glycopeptide antibiotics, such as teicoplanin or vancomycin, are used against methicillin-resistant S. aureus.2

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Spine infections are diagnostically challenging because of the different presentations. Prompt diagnosis and early treatment allows for the best chance for meaningful recovery.19 Spinal infections must be suspected in all patients with severe continuous spine pain with weight loss and unexplained fever. It is only with careful clinical examination, diagnostic testing, and prompt treatment in order to limit the potential damage and disability this condition can produce. These patients have more severe functional impairments on rehabilitation admission and discharge and longer inpatient rehabilitation length of stay.6

Cutting Edge/ Emerging and Unique Concepts and Practice

In light of Staphylococcus aureus being the most common cause of spondylodiscitis, some studies are focused on developing a serum antibody test to help guide prophylaxis and therapy in a future of personalized medicine and pathogen-specific treatments. More specifically, ratios of certain antibody levels could provide a prognostic measure of outcome.20

Vaccines to prevent S. aureus infection has proven to be extremely challenging. However, insights gained from the failures have nevertheless helped in guiding the scientific community to continue innovating and developing diverse vaccines aimed evoking different aspects of the immune system.21

Finally, in a society where increasing antibiotic resistance is responsible for the emergence of multidrug-resistant bacteria, we must find a way to curb inappropriate use. One proposed solution is to have a multifaceted approach that integrates patient-based omics information such as genetic predisposition to infections (genomics), immune response to infection (proteomics and transcriptomics), transcriptomics, proteomics, microbiome, and drug metabolism kinetics to generate accurate physician-friendly algorithms together with comprehensive pathogen profiling. This would result in more accurate diagnosis and appropriate treatments.22

Gaps in the Evidence-Based Knowledge

N/A

References

  1. Lener, Sara et al. “Management of spinal infection: a review of the literature.” Acta Neurochirurgica Vol. 160,3 (2018): 487-496. doi:10.1007/s00701-018-3467-2
  2. Tsantes, Andreas G et al. “Spinal Infections: An Update.” Microorganisms vol. 8,4 476. 27 Mar. 2020, doi:10.3390/microorganisms8040476
  3. Tschugg, Anja et al. “Primary acquired spondylodiscitis shows a more severe course than spondylodiscitis following spine surgery: a single-center retrospective study of 159 cases.” Neurosurgical review vol. 41,1 (2018): 141-147. doi:10.1007/s10143-017-0829-9
  4. Taylor, Davis G et al. “Presentation and Outcomes After Medical and Surgical Treatment Versus Medical Treatment Alone of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review and Meta-Analysis.” Global spine journal vol. 8,4 Suppl (2018): 49S-58S. doi:10.1177/2192568218799058 
  5. Herren C, Jung N, Pishnamaz M, Breuninger M, Siewe J, Sobottke R. Spondylodiscitis: Diagnosis and Treatment Options. Dtsch Arztebl Int. 2017;114(51-52):875-882. doi:10.3238/arztebl.2017.
  6. Brubaker, M L et al. “Clinical features and inpatient rehabilitation outcomes of infection-related myelopathy.” Spinal cord vol. 55,3 (2017): 264-268. doi:10.1038/sc.2016.115.
  7. Sato, Kimiaki et al. “Pyogenic Spondylitis: Clinical Features, Diagnosis and Treatment.” The Kurume medical journal vol. 65,3 (2019): 83-89. doi:10.2739/kurumemedj.MS653001 
  8. Zimmerli W. Clinical practice Vertebral osteomyelitis. N Engl J Med. 2010;362:1022–1029
  9. Ledermann HP, Schweitzer ME, Morrison WB. MR imaging findings in spinal infections: rules or myths? Radiology. 2003:506–514
  10. Berbari EF, Kanj SS, Kowalski TJ, et al. Infectious Diseases Society of America (IDSA): clinical practice for the diagnosis and therapy of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61:26–46
  11. Brown, R., et al., Discitis in young children. J Bone Joint Surg Br, 2001. 83(1): p. 106-11
  12. Colmenero, J.D., et al., Pyogenic, tuberculous, and brucellar vertebral osteomyelitis: a descriptive and comparative study of 219 cases. Ann Rheum Dis, 1997. 56(12): p. 709-15
  13. McHenry, M.C., K.A. Easley, and G.A. Locker, Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis, 2002. 34(10): p. 1342-50.
  14. Liebergall, M et al. “Pyogenic vertebral osteomyelitis with paralysis. Prognosis and treatment.” Clinical orthopaedics and related research ,269 (1991): 142-50.
  15. Dodson, Vincent et al. ” The effect of prophylactic vancomycin powder on infections following spinal surgeries: a systematic review”. Neurosurgical Focus FOC 46.1 (2019): E11. doi.org/10.3171/2018.10.FOCUS18470
  16. Devin, C.J., et al., Intrawound Vancomycin Decreases the Risk of Surgical Site Infection after Posterior Spine Surgery-A Multicenter Analysis. Spine (Phila Pa 1976), 2015.
  17. Ueno, M., et al., Triclosan-coated sutures reduce wound infections after spinal surgery: a retrospective, nonrandomized, clinical study. Spine J, 2015. 15(5): p. 933-8.
  18. Sharma, Mayur et al. ” Insights into complication rates, reoperation rates, and healthcare utilization associated with use of recombinant human bone morphogenetic protein–2 in patients with spine infections”. Neurosurgical Focus FOC 46.1 (2019): E8. doi.org/10.3171/2018.10.FOCUS18448
  19. Nas, Kemal et al. “Rehabilitation in spinal infection diseases.” World journal of orthopedics vol. 6,1 1-7. 18 Jan. 2015, doi:10.5312/wjo.v6.i1.1
  20. Muthukrishnan, Gowrishankar et al. “Serum antibodies against Staphylococcus aureus can prognose treatment success in patients with bone infections.” Journal of orthopaedic research : official publication of the Orthopaedic Research Society vol. 39,10 (2021): 2169-2176. doi:10.1002/jor.24955
  21. Clegg, Jonah et al. “Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies.” Frontiers in immunology vol. 12 705360. 7 Jul. 2021, doi:10.3389/fimmu.2021.705360
  22. Olivier, Michael et al. “The Need for Multi-Omics Biomarker Signatures in Precision Medicine.” International journal of molecular sciences vol. 20,19 4781. 26 Sep. 2019, doi:10.3390/ijms201947810875

Original Version of the Topic 

Sarjoo M. Bhagia, MD, Jamal Balouch, MD, Kartik Swaminathan, MD. Spine Infections. 9/20/2013.

Previous Revision(s) of the Topic 

Vincent Huang, MD, Raman Sharma, MD, Conrad Fischer, MD. Spine Infections. 4/3/2017.

Author Disclosure

Casey A. Murphy, MD, FAAPMR, DAAPM
Nothing to Disclose

Carlos “Coco” Trigo, MD
Nothing to Disclose

Dean John Hendrix Dante
Nothing to Disclose