Infection of the Spine

Spinal infection may be defined as an infectious condition that affects the vertebral body, the intervertebral disk, or adjacent paraspinal tissue. It accounts for 2-7% of all musculoskeletal infections.

Pyogenic vertebral osteomyelitis is the most encountered form of vertebral infection. It can develop from direct open spinal trauma, from infections in adjacent structures, from hematogenous spread of bacteria to a vertebra, or postoperatively. Left untreated, vertebral osteomyelitis can lead to permanent neurologic deficits, significant spinal deformity, or death. It can result in severe compression of the neural structures due to the formation of an epidural abscess or due to a pathologic fracture resulting from bone softening.

Historically, vertebral osteomyelitis was considered primarily a disease of adults. Most cases used to occur in patients older than 50 years; however, with the increased use of intravenous (IV) drugs in younger patients, this condition is increasingly seen in younger patients.

Various organisms can cause osteomyelitis. The microbiology varies with the host’s risk factors and the local epidemiology. The mainstays of treatment are early recognition and antibiotics.

The overall treatment plan for a patient with vertebral osteomyelitis must be individualized according to the patient’s general medical condition, his or her neurologic status, the presence of large associated abscesses, and biomechanical factors. Most patients with pyogenic vertebral osteomyelitis respond to medical management. However, surgery may be required if medical management is unsuccessful. Scoring systems have been developed to help in making the decision between nonsurgical and surgical treatment.

Although successful treatment of spinal abscess with surgical drainage was reported early on, the high complication rate from secondary infection caused this surgery to remain in poor favor. Following the introduction of antisepsis, surgical intervention for spinal infections became feasible.

The initial procedure introduced for the surgical treatment of spinal infections was a laminectomy. However, this procedure did not allow access to anterior abscesses and contributed to spinal instability, which often resulted in progressive deformity.

Ito et al first described the anterior approach to the spine. Later, Hodgson et al extensively reported this procedure in the treatment of tuberculosis of the spine. Late spinal deformity was prevented with spinal fusion and instrumentation. Whereas Hodgson et al performed fusions from the anterior approach, Hibbs et al independently presented techniques for posterior spinal fusion in the treatment of spinal tuberculosis.

In the future, the introduction of newer, more effective antibiotics, the application of slow-release topical antibiotics to the surgical site, and, possibly, the use of monoclonal antibody treatment may improve the treatment of these infections. For patients requiring a fusion procedure, the use of growth factors for the induction of spinal fusions is a theoretically attractive approach. Numerous studies have shown that viral vectors can be used to implant osteoinductive growth factor genes directly into the paraspinal muscles or into cells that can subsequently be implanted next to the spine. These osteoinductive factors enhance the activation and differentiation of pluripotent stem cells to develop into mature bone.

Anatomy

The anatomy of the spine includes the vertebral bodies, the intervertebral disks, and associated joints, muscles, tendons, ligaments, and neural elements.

The intervertebral disk is a fibrocartilaginous remnant of the embryonic notochord, which provides the spine with strength, mobility, and resistance to strain. It consists of the following three parts:

Annulus fibrosus
Nucleus pulposus
Cartilaginous endplates

The annulus fibrosus is made up of type I collagen fibrils, which are arranged in 15-20 concentric lamellae brought together into parallel bundles. These bundles are firmly attached to the vertebral bodies and are arranged in layers to provide strength and limit vertebral movement when the disk is compressed. The nucleus pulposus is composed of type II collagen and represents 30-60% of the disk volume. The nucleus pulposus is supplied with blood vessels through small perforations in the central cartilaginous endplates.

The cervical spine consists of the first seven vertebrae in the spinal column (C1-7). Typically, these vertebrae are small and possess a foramen on the transverse process for the vertebral artery. The thoracic spine consists of the next 12 vertebrae (T1-12) and is stabilized by the attached rib cage and intercostal musculature. The lumbar spine consists of a mobile segment of five vertebrae (L1-5), located between the relatively immobile segments of the thoracic and sacral segments.

The lumbar vertebrae are particularly large and heavy in comparison with the cervical and thoracic vertebrae. The bodies are wider and have shorter and heavier pedicles, and the transverse processes project somewhat more laterally and ventrally than the other spinal segments. The laminae are shorter vertically than the bodies and are bridged by strong ligaments. The spinal processes are broader and stronger than those in the thoracic and cervical spine.

Pathophysiology

Approximately 95% of pyogenic spinal infections involve the vertebral body; only 5% involve the posterior elements of the spine. This disparity has been attributed in part to the voluminous blood supply to the vertebral body and its rich, cellular marrow.

Bacteria circulating through the blood may enter a vertebra or a disk space via its arterial blood supply or via the venous system. In the typical case, bacteria enter the vertebral body through small metaphyseal arteries arising from larger primary periosteal arteries that, in turn, branch from spinal arteries. In adults, blockage of metaphyseal arteries by septic thrombi may infarct relatively large amounts of bone. Subsequently, bacteria can readily colonize a large bony sequestrum adjacent to the disk.

In the adult, after bacterial colonization of the metaphyseal region, the avascular disk is secondarily invaded by bacteria from the endplate region. Intermetaphyseal communicating arteries allow the spread of septic thrombi from one metaphysis to the other in a single vertebral body without the involvement of the midportion of the vertebra.

Although the arterial route is the usual route of bacterial spread to a vertebra, another proposed route of infection is the retrograde seeding of venous blood via the Batson plexus. During periods of increased intra-abdominal pressure, venous blood is shunted toward the vertebral venous plexus. Some authors have proposed that the venous system may be the route of bacterial spread from genitourinary (GU) tract infections.

Another possible means of infection is by the spread of contiguous infection into the vertebrae and disk (e.g., from a retropharyngeal abscess or a retroperitoneal abscess), resulting in osteomyelitis and diskitis.

Etiology

Presumably, a distant focus of infection provides an infective nidus from which bacteria spread by the bloodstream to the spinal column. The skin and the GU tract are common antecedent sites, but a review of the literature reveals multiple foci, such as septic arthritis, sinusitis, subacute bacterial endocarditis, and respiratory, oral, or gastrointestinal (GI) infections. Approximately 30-70% of patients with vertebral osteomyelitis have no obvious prior infection.

Risk factors for developing osteomyelitis include conditions that compromise the immune system, such as the following:

Tobacco use
Advanced age
IV drug use and narcotic addiction
Congenital immunodepression
Long-term systemic administration of steroids
Diabetes mellitus
Organ transplantation
Malnutrition
Cancer
Rheumatoid arthritis (RA)

It is well known that chronic tobacco use increases the risk of infection and delays wound healing. Smoking just one cigarette decreases the body’s ability to deliver the necessary nutrients for healing after surgery. Smoking is associated with an increased risk of wound infections even for simple wounds. It has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions, leading to delayed healing and complications.

IV drug abuse is a growing cause of spinal infections. Typically, the organism most likely to infect the spine is Staphylococcus aureus; however, in IV drug users, Pseudomonas species are also a common cause. Nonpyogenic osteomyelitis can be caused by tuberculosis, fungus, yeast, or parasitic organisms.

It is also known that chronic narcotic use and addiction depress the immune system, increasing the risk of infection. Perhaps the most notable study on the relation between opioid exposure and wound healing outcomes was performed at George Washington University in Washington, DC, using patient data collected through the Wound Etiology and Healing study in a longitudinal cohortThe authors discovered a strong correlation between opioid use and slower healing rates in patients who received opioid dosages higher than 10 mg/day. These results were arguably the first major findings on the association between slower healing rates and increased opioid exposure.

Surgical-site infection (SSI) can result in an adverse event after a spinal procedure. Appropriate timing of preoperative antibiotic prophylaxis, as well as careful aseptic technique, can reduce the incidence of SSIs during spinal procedures. At present, there is not enough evidence to support the routine use of vancomycin powder after routine spine surgery. Cervical anaerobic vertebral osteomyelitis has been reported following surgical tracheotomy.

Fungal infections of the spine are rare and generally occur in patients who are debilitated or have diabetes or a compromised immune system. Patients with acute leukemia, alcoholics, patients with lymphoma, recipients of organ transplants, and those receiving chemotherapy are particularly susceptible to fungal infections.

Most vertebral body infections occur in the lumbar spine because of the blood flow to this region of the spine. Tuberculosis has a predilection for the thoracic spine, and IV drug abusers are more likely to contract an infection of the cervical spine.

RA is a chronic autoimmune systemic inflammatory disorder that manifests as inflammation of synovial joints, leading to joint destruction and deformity. Although it is not a fatal disease in general, associated complications (e.g., heart diseases and respiratory problems) can lead to increased mortality. A review of the literature by Zhang et al concluded that patients with RA who undergo spinal surgery had a greater risk of operative complications and infection; however, the use of biological disease-modifying antirheumatic drugs (DMARDs) did not significantly increase the risk of infection associated with spinal surgery in these patients.

There is no cure for RA, but these patients are usually on long-term DMARD therapy to suppress joint inflammation, minimize joint damage, preserve joint function, and keep the disease in remission. RA is strongly associated with various immune cells, and each of the cell types contributes differently to its pathogenesis. Several types of immunomodulatory molecules (mainly cytokines secreted from immune cells) mediate the pathogenesis of RA, complicating the treatment and management of the disease.

Epidemiology

United States statistics

Vertebral osteomyelitis is considered uncommon, with an incidence of 1 case per 100,000-250,000 population per year. However, some reviews have suggested that the incidence of spinal infections is increasing. This increase may be secondary to increased use of vascular devices and other forms of instrumentation and to increasing rates of IV drug abuse. Because of its rarity and vague initial signs and symptoms, diagnosis is often delayed.

In a 2013 study by Issa et al, the incidence of admission for vertebral osteomyelitis was 4.8 per 100,000, increasing from 8021 cases (2.9/100,000) in 1998 to 16,917 (5.4/100,000) in 2013. The majority of the patients were white (74%), male (51%), and younger than 59 years (49.5%).

International statistics

In developed nations, the incidence of spinal osteomyelitis is like that in the United States. However, in less developed nations, infectious osteomyelitis is more common. In some areas of Africa, a reported 11% of all patients seen for back pain were diagnosed with diskitis and osteomyelitis.

Age-, sex-, and race-related demographics

A bimodal age distribution occurs in diskitis. Diskitis and osteomyelitis peak in pediatric patients; the incidence of spinal infections then decreases until middle age, when a second peak in incidence is observed at approximately age 50 years. Some authors have argued that childhood diskitis is a separate disease entity and should be considered independently.

Osteomyelitis has a predilection for males.

No specific predilection for a particular race has been noted.

Prognosis

Both bony and neural status must be considered in the evaluation of treatment outcome. Most patients can be cured by a treatment protocol that includes antibiotics alone or in combination with surgery. For patients with an incomplete neurologic compromise, several studies indicate that with aggressive antibiotic and surgical therapy, paresis may improve or resolve. Only 15% of patients experience permanent neurologic deficits. Recrudescence of infection occurs in 2-8% of patients.

In a retrospective cohort study, Gupta et al assessed 260 patients with pyogenic vertebral osteomyelitis, of whom 27% acquired the infection after an invasive spinal procedure, 40% had S aureus as the cause of the infection, and 49% underwent spinal surgery as part of initial therapy. The estimated cumulative probability of treatment failure-free survival was 72% at 2 years, 69% at 5 years, and 69% at 10 years. On multivariate analysis, the following factors were associated with a greater likelihood of treatment failure:

Longer duration of symptoms before diagnosis
Infection caused by S aureus

In the elderly, the global 1-year mortality associated with pyogenic vertebral osteomyelitis is higher than in younger patients, though the initial presentation does not differ significantly regarding either symptoms or severity. Microbiologic findings differ in the elderly, who have fewer staphylococcal infections but more infections caused by streptococci or methicillin-resistant S aureus (MRSA). The higher mortality in the elderly may be explained by a higher frequency of associated infective endocarditis and a higher comorbidity rate.

History

The onset is usually insidious. Back pain is the most common symptom. Most patients have a history of several weeks or months of gradually progressing neck or back pain that increases with movement. The pain is initially localized at the level of the involved area and gradually increases in intensity. Thereafter, the pain eventually becomes so severe that it is not relieved by analgesics or even complete bed rest. Usually, neurological signs are not present until late in the disease course and may be associated with the destruction and collapse of the vertebral body.

Children with vertebral osteomyelitis and associated diskitis usually present with an abrupt onset of malaise, fever, and back pain. They commonly demonstrate back stiffness, restricted motion, guarded walking, and spine tenderness. Some patients can also present acutely with fever, night sweats, elevated leukocyte counts, and signs and symptoms of shock.

Physical Examination

In the typical case with mild symptoms, physical examination reveals only mild tenderness over the spinous process of the involved vertebra, and minimal spasm may be present in nearby paravertebral muscles. Decreased range of motion (ROM) is also common. Only about half of patients are febrile.

Later, neurologic compromise is caused by bony collapse, spread of the infection underneath the posterior longitudinal ligament, or frank epidural abscess with compression of the spinal cord or nerve roots. A progression to radicular signs followed by weakness and paralysis suggests the formation of an epidural abscess. Spinal epidural abscess occurs in 5-18% of cases and is most commonly located anteriorly in the epidural space. Cervical vertebral osteomyelitis is associated with paralysis more commonly than either thoracic or lumbar infection.

In patients with neurologic compromise, a detailed motor and sensory examination should be performed. Muscle strength and weakness are graded on a scale of 0 to 5, with a strength of 0/5 representing paralysis and a strength of 5/5 considered normal, as follows:

0 – No contraction
1 – Flicker of movement
2 – Can move when gravity is eliminated
3 – Can elevate against gravity
4 – Can move against resistance (–4, slight resistance; 4, moderate resistance; +4, strong resistance)
5 – Normal strength

The sensory examination should include detection of a sensory level, posterior column function, normal and abnormal reflexes, and examination of rectal tone and perianal sensation. The presence of a Babinski sign should also be noted and documented. The neurologic examination should be repeated and documented at regular intervals to serve as a reference for improvement or deterioration of the patient’s neurologic status over time.

Complications

Patients who die of vertebral osteomyelitis typically succumb to the spinal-neural infection or to other attendant problems, such as secondary sepsis, inanition, or the original infection. The mortality for osteomyelitis ranges from 2% to 12%. Neurologic deficits develop in 13-40% of patients, especially those with diabetes or other systemic illnesses.

Approach Considerations

The Infectious Diseases Society of America (IDSA) has published clinical practice guidelines for the diagnosis of native vertebral osteomyelitis (NVO) in adults.

Although magnetic resonance imaging (MRI) is the method of choice for vertebral osteomyelitis and diskitis in the early stages, it may show only subtle, nonspecific endplate subchondral changes; a repeat examination may be required to demonstrate the typical features.

Computed tomography (CT) is useful for assessing bony destruction and instability in patients with destructive lesions. Flexion-extension radiographs are also useful for diagnosing biomechanical instability.

The implementation of artificial intelligence (AI) technology in orthopedic imaging may improve physicians’ ability to diagnose NVO accurately, as well as reduce their workloads.

Blood tests (e.g., complete blood count [CBC], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP] level) are nonspecific markers of inflammation. The gold standard diagnostic test is a biopsy with tissue cultures for microbiology.

Laboratory Studies

Leukocytosis, the usual indication of infection, is often absent or minimal in patients with chronic pyogenic vertebral osteomyelitis.

Elevation of the ESR, though nonspecific, is the most common laboratory abnormality. Back pain coupled with an increased ESR should lead the clinician to suspect vertebral disease (e.g., infection, neoplasia, or rheumatoid disorder).

Blood cultures should always be obtained before the administration of antibiotics.

CRP, synthesized by hepatocytes, is an excellent indicator of inflammation. Patients with bacterial diskitis have higher serum CRP and fibrin levels. Patients with nonseptic diskitis (i.e., chemical diskitis) have only dense fibrotic histologic changes, and serum CRP and fibrin findings are normal.

The use of soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a means of distinguishing vertebral osteomyelitis from degenerative diseases of the spine. In a study by Scharrenberg et al, suPAR was found to be less sensitive but more specific than CRP for this purpose, suggesting that diagnostic power might be enhanced by combining the two.

Plain Radiography

The process of diagnosing a spinal infection usually begins with a radiograph, though radiographic findings are usually normal in the first 2-4 weeks. If the disk space is involved (diskitis), the disk space may narrow, and destruction of the endplates around the disk may be seen on the radiograph. (See the image below.)

Spinal infections. Lateral plain radiographs of Patient A with diskitis at C4-5. Note that severe disk space narrowing and subluxation are seen at C4-5.

Later, plain radiographs usually reveal rarefaction, loss of bony trabeculation close to the cartilaginous plate, and irregular narrowing of the vertebral disk space. Vertebral body collapse may also be seen (see the image below). Simultaneously, evidence of rapid bone regeneration may be evident, with the development of bone spurs and dense new bones. A paravertebral soft-tissue mass may also be present.

Spinal infections. Patient B (47-year-old woman) presented with intractable back pain. Radiographs reveal significant collapse and destruction of the L4 vertebral body. MRI of the lumbar spine was ordered.

CT and PET

CT depicts osteomyelitis earlier than plain films do. CT findings include hypodensity at the site of infected disks, lytic fragmentation of the involved bone, gas within an involved vertebra, and decreased density of adjacent vertebrae and nearby soft tissues. Epidural and paraspinal extension of infection may also be seen.

The use of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in conjunction with CT is helpful in the diagnosis of vertebral osteomyelitis. In a study by Kouijzer et al, which compared ¹⁸F-FDG-PET/CT and MRI with the clinical diagnosis, ¹⁸F-FDG-PET/CT had a sensitivity of 100%, a specificity of 83.3%, a positive predictive value of 90.9%, and a negative predictive value of 100% for diagnosing vertebral osteomyelitis. In particular, ¹⁸F-FDG-PET/CT had an advantage for visualization of metastatic infection, especially in bacteremic patients.

A study of 133 cases of vertebral osteomyelitis by Russo et al found FDG-PET/CT to be more reliable than MRI for follow-up of infection.

Magnetic Resonance Imaging

MRI of the spine provides information that CT does not.

Characteristic MRI findings include destructive and expansile lesions involving two adjacent vertebrae and their intervening disk.

Low-density changes in bone and disk are seen on T1-weighted images, whereas high-density changes are seen in these structures on T2-weighted images, presumably from their increased water content. Intravenous (IV) infusion of gadolinium shows enhancement of the involved structures. Paravertebral infection, collections under the posterior longitudinal ligament, and epidural abscesses may also be shown. (See the images below.)

MRI of Patient B reveals enhancing mass affecting the L4 vertebral body with compromise of the spinal canal. The patient underwent several blood cultures and CT-guided trocar biopsy; the culture results were negative. The surgical procedure was necessary.

Spinal infections. T2-weighted MRI of Patient A. Evidence of osteomyelitis and diskitis, as well as a small epidural abscess, is present. The patient underwent C4-5 anterior cervical diskectomy and arthrodesis using an autologous iliac crest bone graft and instrumental fixation with titanium plate and screws.

Diffusion-weighted imaging is useful in distinguishing between degenerative and infectious endplate abnormalities. Compared with PET, diffusion-weighted MRI costs less, has faster imaging times, and does not involve the use of ionizing radiation.

Radionuclide Scanning

Radionuclide scans with technetium-99m are very sensitive early indicators of pyogenic vertebral osteomyelitis. Radionuclide scan findings become positive long before plain film changes are evident.

Technetium-99m bone scanning is not useful for specifically differentiating infection from metastasis or osteoarthritis. Gallium is more likely to localize an inflammatory lesion, and technetium-99m combined with gallium-167 demonstrates virtually all pyogenic vertebral infections.