Practice Essentials
Spinal infection may be defined as an infectious disease that affects the vertebral body, the intervertebral disk, or adjacent paraspinal tissue. [1] It accounts for 2-7% of all musculoskeletal infections.
Pyogenic vertebral osteomyelitis is the most commonly encountered form of vertebral infection. [2] 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. [3, 4, 5, 6, 7, 8, 9] It can result in severe compression of the neural stuctures due to formation of an epidural abscess or due to a pathologic fracture resulting from bone softening.
Evidence of vertebral osteomyelitis has been found in Egyptian mummies. Hippocrates first described the infection of the vertebral column. Later, Galen related this infectious process to spinal deformity. Before the development of antibiotics and bacteriology, little knowledge was added to the basic understandings of the Hippocratic school until Servino and Potts characterized and described the pathology of tuberculosis infection of the spine. In 1879, Lannelonge described bacterial osteomyelitis as we recognize it today.
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. [10]
Various different 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. (See 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:
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Anulus fibrosus
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Nucleus pulposus
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Cartilaginous endplates
The anulus 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 the 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 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 tract infections.
Another possible means of infection is by the spread of contiguous infection into the vertebrae and disk (eg, from a retropharyngeal abscess or a retroperitoneal abscess), resulting in osteomyelitis and diskitis. [11]
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 genitourinary 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) infection. [12, 13, 14, 15] 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:
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Tobbacco use
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Advanced age [16]
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IV drug use and narcotic addiction [17]
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Congenital immunodepression
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Long-term systemic administration of steroids
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Organ transplantation
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Malnutrition
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Cancer
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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 necessary nutrients for healing after surgery. Smoking is associated with an increased risk of wound infections even for simple wounds, according to the results of a 2012 randomized controlled trial by Sorensen et al. [19] Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions, leading to delayed healing and complications. [20, 21, 22, 23]
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. [24] Nonpyogenic osteomyelitis can be caused by tuberculosis, fungus, yeast, or parasitic organisms. [25, 26, 27, 28, 29, 30]
It is also known that chronic narcotic use and addiction depress the immune system, increasing the risk of infection. [31, 32] 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 cohort (N = 450). [33] The authors discovered a strong correlation between opioid use and slower healing rates in patients who received opioid dosages greater than 10 mg/day. These results are arguably the first major findings on the association between slower healing rates and increased opioid exposure.
Surgical-site infection (SSI) can result as 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. [34, 35, 36, 37, 38] At present, there is not enough evidence to support routine use of vancomycin powder after routine spine surgery. [39] Cervical anaerobic vertebral osteomyelitis has been reported following surgical tracheotomy. [40]
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 [41, 28]
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. [25]
RA is a chronic autoimmune systemic inflammatory disorder that manifests as inflammation of synovial joints, leading to joint destruction and deformity. [42] Although it is not a fatal disease in general, associated complications (eg, heart diseases and respiratory problems) can lead to increased mortality. [43] 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, they found that the use of biologic disease-modifying antirheumatic drugs (DMARDs) did not significantly increase the risk of infection associated with spinal surgery in these patients. [44]
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, compluicating 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. [45] 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%). [46]
International statistics
In developed nations, the incidence of spinal osteomyelitis is similar to 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. [47] Some authors argue 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. [48] Most patients can be cured by a treatment protocol that includes antibiotics alone or in combination with surgery. [49, 50] For patients with an incomplete neurologic compromise, several studies indicate that with aggressive antibiotic and surgical therapy, paresis may improve or resolve. [51, 52, 53] 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. [54] 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 greater likelihood of treatment failure:
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Longer duration of symptoms before diagnosis
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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 with regard to either symptoms or severity. [55] 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.
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Spinal infections. Lateral plain radiographs of Patient A with diskitis at C4-5. Note severe disk space narrowing and subluxation seen at C4-5.
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Spinal infections. T2-weighted MRI of Patient A. Evidence of osteomyelitis and diskitis, as well as small epidural abscess, is present. The patient underwent C4-5 anterior cervical diskectomy and arthrodesis using autologous iliac crest bone graft and instrumental fixation with titanium plate and screws.
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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 lumbar spine was ordered.
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MRI of Patient B reveals enhancing mass affecting L4 vertebral body with compromise of spinal canal. Patient underwent several blood cultures and CT-guided trocar biopsy; culture results were negative. Surgical procedure was necessary.
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Spinal infections. Patient B developed lower-extremity weakness, and follow-up studies reveal further compression of L4 and compromise of canal. Anterolateral approach was performed with corpectomy, decompression of spinal canal, restoration of anterior column support, and arthrodesis with titanium cage and autologous iliac crest bone graft. Pathology and Gram stain revealed some hyphae. Culture findings were positive for Aspergillus species. Patient underwent full course of amphotericin B and completely recovered.
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MRI with gadolinium contrast in 41-year-old patient with history of IV drug use and extensive osteomyelitis, diskitis, and anterior spinal epidural abscess causing compression of spinal cord.
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Intraoperative fluoroscopy in 41-year-old patient with history of IV drug use and extensive osteomyelitis, diskitis, and anterior spinal epidural abscess treated with corpectomy and anterior stabilization.
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AP intraoperative fluoroscopy. Given abnormal softening of bones by osteomyelitis, same patient underwent posterior stabilization of spine with lateral mass and pedicle screws.
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3D CT of 41-year-old man with severe osteomyelitis and diskitis at L3 and L4. Note bony destruction. This was later demonstrated with gadolinium-enhanced MRI.
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Gadolinium-enhanced MRI in 37-year-old male with history of IV methamphetamine use who developed severe diskitis at L3-4. Epidural abscess is also present. Treatment of his condition required extensive surgical decompression and stabilization. Cultures showed polymicrobial infection, including gram-positive and gram-negative bacteria. Antibiotic beads soaked in vancomycin and tobramycin were applied to surgical site.
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Gadolinium-enhanced MRI in 67-year-old male with L3-4 and L4-5 diskitis. Initial cultures were negative. He was treated medically with 8 weeks of IV antibiotics and clinical follow-up with ESR and CRP.
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Same patient presented several months later with intractable pain. His CT and MRI showed extensive destruction of disks and vertebral bodies. His condition required extensive debridement with stabilization of spine using transpedicular screws and rods. Antibiotic beads were placed at surgical site.
