Spinal Infections

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:

• Anulus fibrosus
• Nucleus pulposus
• 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.

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]

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:

• Tobbacco use
• Advanced age ^[16]
• IV drug use and narcotic addiction  ^[17]
• Congenital immunodepression
• Long-term systemic administration of steroids
• Diabetes mellitus ^[18]
• 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 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.

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. 

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:

• 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 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. 

The onset is usually insidious. Back pain is the most common symptom.[56] 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 bedrest. Usually, neurologic signs are not present until late in the disease course and may be associated with destruction and collapse of the vertebral body.[57]

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.

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.[58] 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.[3]

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.

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.

The Infectious Diseases Society of America (IDSA) has published clinical practice guidelines for the diagnosis of native vertebral osteomyelitis (NVO) in adults (see Guidelines).[59]

Although magnetic resonance imaging (MRI) is the imaging 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 patient with destructive lesions. Flexion-extension radiographs are also useful for diagnosing biomechanical instability.

Blood tests (eg, 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.[60, 61, 62]

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 (eg, infection, neoplasia, or rheumatoid disorder).

Blood cultures should always be obtained before 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 (ie, 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.[63]

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 severe disk space narrowing and subluxation 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 bone. 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 lumbar spine was ordered.

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.[64] 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.[65]

MRI of the spine provides information that CT does not.[66, 67]  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 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.

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.

Diffusion-weighted imaging is useful in distinguishing between degenerative and infectious endplate abnormalities.[68] Compared with PET, diffusion-weighted MRI costs less, has faster imaging times, and does not involve the use of ionizing radiation.[69]

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.[70]

In the past, myelography was used in the evaluation of vertebral osteomyelitis to delineate areas of epidural spread and neural compression. MRI has largely supplanted myelography because of its ability to depict not only bony changes but also pus and granulation tissue under the posterior longitudinal ligament and epidural infection.

Patients with vertebral osteomyelitis can develop urinary retention. Urodynamic studies may be helpful. Methods of objectively testing the behavior of the lower urinary tract during filling, storage, and micturition include the following:

• Uroflowmetry
• Cystometry
• Sphincteric electromyography (EMG)
• Combined studies

When appropriately used, urodynamic testing provides valuable information for the evaluation and subsequent treatment of neurourologic dysfunction.

CT-guided percutaneous biopsy of the infected vertebra or disk may be done via a needle or trocar. Findings are positive only 60-70% of the time. This is a minimally invasive test used to obtain histologic confirmation of the disease and tissue samples for culture. Trocar biopsies have proved more useful than fine-needle aspiration (FNA) because they allow a larger amount of material from the infected area to be examined histologically, as well as cultured. Fluoroscopy may be an option for biopsy guidance if CT is not available.[71]

As with blood cultures, the likelihood of positive tissue culture findings decreases if antibiotic therapy has already been initiated. A 10-year retrospective review suggested that paravertebral soft tissues may also be considered viable biopsy targets.[72]

If blood cultures and percutaneous biopsy fail to identify the infecting organism, open surgical biopsy is indicated. An open surgical biopsy has the highest yield in terms of positive culture findings and diagnostic confirmation.[73]

Histologic findings are similar to those of any bacterial pyogenic infection. Local destruction of the disk and endplates occurs with infiltration of neutrophils in the early stages. Later, a lymphocytic infiltrate predominates.

The combination of mechanical compression of the spinal cord by pus or granulation tissue can result in ischemia with spinal cord infarction, which accounts for the rapid neurologic progression of this disease. Patients with a spinal epidural abscess may progress to complete paralysis within minutes to hours, even while receiving optimal antibiotic therapy. In addition, patients with vertebral osteomyelitis can develop pathologic fractures, caused by the softening of the bone, and present with acute spinal cord compression.

Most patients with pyogenic vertebral osteomyelitis respond to medical management. However, surgery may be required if medical management is unsuccessful.[74] Indications for surgery include the following:

• Significant osseous involvement
• Neurologic deficits - Neurologic deterioration can be caused by significant kyphosis, by infection behind the vertebral body under the posterior longitudinal ligament, or by infection in the epidural space
• Septic course with clinical toxicity from an abscess not responding to antibiotics
• Failure of needle biopsy to obtain necessary cultures
• Failure of intravenous (IV) antibiotics alone to eradicate the infection

The Infectious Diseases Society of America (IDSA) has published clinical practice guidelines for the treatment of native vertebral osteomyelitis (NVO) in adults (see Guidelines).[59]

Removal of hardware with irrigation and debridement in patients with surgical-site infections (SSIs) is performed commonly. However, the removal of hardware from patients with SSIs after spinal procedures is controversial.[75]  Moreover, new spinal infections with spinal cord compression or biomechanical instability may require instrumentation[76, 77, 78] along with surgical debridement. In these patients, topical placement of antibiotic-impregnated beads, which allow slow release of antibiotics, may be beneficial. 

There has been a growing emphasis on the use of newer minimally invasive surgical approaches to treat spinal infections.[79, 80]

The overall treatment plan for a patient with vertebral osteomyelitis must be individualized according to the patient's general medical condition,[54, 55, 81, 82] his or her neurologic status, the presence of large associated abscesses, and biomechanical factors. Underlying infections (eg, retropharyngeal, pelvic, decubital) must be treated simultaneously if the vertebral infection is to be cured. A multidisciplinary approach is very important.[41, 83, 84]

Antibiotic treatment must be tailored to the isolated organism and any other sites of infection. Broad-spectrum antibiotics covering both gram-positive and gram-negative organisms, aerobes and anaerobes (including methicillin-resistant S aureus [MRSA]), are administered initially until the organism is isolated. Most cases of vertebral osteomyelitis are caused by S aureus, which generally is sensitive to antibiotics. Although rare, spinal tuberculosis or fungal infection must be considered in the face of persistently negative culture findings and lack of response to antibiotics.[4, 85, 86]

Antibiotics are given for variable lengths of time. It appears that 6-8 weeks of parenteral antibiotic therapy is effective in most cases[85, 86]  Before parenteral antibiotics are discontinued, the erythrocyte sedimentation rate (ESR) should have fallen to at least two thirds of the pretherapy level. In addition, the patient should be afebrile, without pain on mobilization, and without any disease-related complications such as neurologic deficits.

A persistently high ESR implies continuing infection, and additional IV antibiotics are indicated. In such an instance, an additional biopsy can be taken of the infected vertebra to see if organisms not susceptible to the chosen antibiotics are present.[60, 62]

Bracing is recommended to provide stability for the spine while the infection is healing. The goal of immobilization is to provide opportunity for the affected level to fuse in an anatomically aligned position. Bracing is usually continued for 6-12 weeks, until either bony fusion is seen on radiographs or the patient's pain subsides. A rigid brace works best and need be worn only when the patient is active.

After successful conservative treatment of pyogenic vertebral osteomyelitis and eventual union, some degree of vertebral body collapse may still occur. The greater the amount of bone destruction present before treatment, the greater the likelihood of eventual kyphosis. After antibiotic treatment, therefore, the spine must be monitored with sequential radiographs. Kyphosis formation may lead to eventual neural impingement, and the kyphosis itself may require late surgical correction.

Medications

Vancomycin is a potent antibiotic that is directed against gram-positive organisms and is active against Enterococcus species. It is useful in the treatment of bloodstream infection and skin-structure infection and is indicated in patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci.

To avoid toxicity, it is recommended to assay vancomycin trough levels after the third dose is drawn one half hour before the next dose. Creatinine clearance (CrCl) should be used to adjust the dose in patients diagnosed with renal impairment. Vancomycin is used in conjunction with gentamicin for prophylaxis in patients who are allergic to penicillin and are undergoing gastrointestinal (GI) or genitourinary (GU) procedures. The adult dosage is 0.5-2 g/day IV; the pediatric dosage is 40 mg/kg/day IV. Vancomycin is a pregnancy category C drug.

Nafcillin is the initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Parenteral therapy should be provided initially in severe infections, then switched to oral therapy as the patient’s condition warrants. Because of the risk of thrombophlebitis, particularly in elderly patients, parenteral administration should continue for only a short period (1-2 days) before being changed to the oral route as clinically indicated.

Adult dosing of nafcillin is 1 g IV or intramuscularly (IM) every 4-6 hours. Neonatal dosing (0-4 kg) is 10 mg/kg IM every 12 hours. Dosing in children who weigh 4-40 kg is 25 mg/kg IM every 12 hours or 50 mg/kd/day orally in four divided doses or, alternatively, 100-200 mg/kg/day IV/IM in four or six divided doses. Nafcillin is a pregnancy category B drug.

Gentamicin is an aminoglycoside antibiotic that has gram-negative coverage. It is used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Gentamicin may be considered if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms. Dosing regimens are numerous; the dosage should be adjusted on the basis of CrCl and changes in volume of distribution. Gentamicin may be given IV or IM.

In adults, dosing of gentamicin for serious infections and normal renal function is 3 mg/kg IV every 8 hours. The loading dose and the maintenance dose are 1-2.5 mg/kg IV and 1-1.5 mg/kg IV, respectively, every 8 hours. The extended dosing regimen for life-threatening infections is 5 mg/kg/day IV/IM every 6 or 8 hours. Each regimen is followed by at least a trough level drawn on the third or fourth dose (30 minutes before dosing); a peak level may be drawn 30 minutes after a 30-minute infusion.

In children younger than 5 years, gentamicin dosing is 2.5 mg/kg IV/IM every 8 hours. In those older than 5 years, dosing is 1.5-2.5 mg/kg IV/IM every 8 hours or 6-7.5 mg/kg/day in three divided doses, not to exceed 300 mg/day, monitored as in adults.

Ceftazidime is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftazidime arrests bacterial growth by binding penicillin-binding proteins. Adult dosing is 1-2 g IV/IM every 8 or 12 hours. Neonatal dosing is 30 mg/kg IV every 12 hours. In infants and children, dosing is 30-50 mg/kg IV every 8 hours, not to exceed 6 g/day. Ceftazidime is a pregnancy category B drug.

A multicenter retrospective cohort study by Watkins et al evaluated ceftaroline, an advanced cephalosporin with activity against MRSA, against a comparator antibiotic in the treatment of spinal infections.[81]  There were no significant differences between the two groups in terms of clinical success, and side effects and toxicities were rare. The investigators concluded that ceftaroline appeared to be safe and effective for treating spinal infections, including those caused by MRSA. 

Although most patients with pyogenic vertebral osteomyelitis respond to medical management, surgery may be required (see Approach Considerations).[4, 87, 88, 49, 50, 51, 52, 53, 89, 90, 91]  Predictors of the need for surgical invention at initial presentation of spinal infection include the presence of epidural abscess, involvement of the cervical or thoracic spine, and an increasing number of spinal levels involved.[92]

Goals of surgery include preservation of neural function and achievement of stable bony fusion without severe kyphosis, which itself could lead to neural compromise or disabling radicular pain.

Preparation for surgery

Most patients who need to undergo a surgical procedure for the treatment of a vertebral infection are chronically debilitated and require a careful preoperative evaluation, including a hematologic and coagulation profile, chest radiography, and electrocardiography (ECG). Blood is typically typed and cross-matched.

Accurate preoperative documentation of the patient's neurologic condition is essential. In patients with spinal instability or spinal cord compression, particular care should be taken to avoid unnecessary movement of the spine during transport, induction of anesthesia, endotracheal intubation, and positioning. Patients with a full stomach undergoing emergency surgery should have gastric decompression via a nasogastric tube and suction. Patients with cervical spinal instability or cervical spinal cord compression may benefit from fiberoptic endotracheal intubation while awake.

If antibiotic therapy has not been initiated preoperatively, prophylactic antibiotics are generally administrated after the cultures have been obtained. However, when the need for spinal instrumentation is anticipated, it is the author's preference to start IV antibiotics preoperatively so as to minimize bacteremia and reduce the chances of chronic persistent infection at the instrumentation.

Operative details

Infections located in the vertebral body or spinal cord compression produced by collapse of the vertebral body are best corrected by an anterior or anterolateral surgical approach (see the image below), which allows one to decompress the neural elements and to remove the infected disk and involved vertebral bodies. Patients with extensive vertebral destruction usually require instrumentation and fusion.

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.

In cases of posterior osteomyelitis, especially if a posteriorly placed epidural abscess is present, laminectomy may be indicated. Whether subsequent fusion should be performed depends on the extent of bone removal, the condition of the anterior spinal column, and the likelihood of postoperative spinal instability or deformity.

After the patient is under general anesthesia and the endotracheal tube is secured, the patient's eyes should be well lubricated and taped shut. A Foley catheter is placed, and bilateral thromboembolism-deterrent (TED) hose and sequential compression boots are used. The extremities should be padded carefully to prevent compression-related neural injury.

Patient positioning depends on the particular surgical approach; the preferred position is usually prone for a posterior approach, supine for an anterior approach, and oblique for an anterolateral approach. It is important to avoid applying pressure to the thorax and abdomen so that epidural bleeding can be minimized.[92]

Decompression of the spinal cord and nerve roots with drainage of purulent material and debridement of compressive granulation tissue is central to this procedure. A full set of aerobic, anaerobic, fungal, and acid-fast bacteria cultures should be obtained early in the procedure. Appropriate antibiotics should be administrated at this time. Debridement and drainage should be followed by extensive irrigation with antibiotic solution. In most cases, closure can be done primarily, with a surgical drain left in place.

In some patients, arthrodesis with internal instrumental fixation may be necessary at the time of decompression.[87, 88, 89] Some patients may benefit from the use of vacuum-assisted wound closure.[90] There is strong support in the literature for a staged anterior decompression and strut fusion followed by a second-stage posterior spinal fixation. However, there is also growing support in the literature for the view that in selected patients, anterior fixation can be combined with a strut fusion or a cage filled with autologous bone.[87, 88, 93, 94] The authors prefer the use of a titanium implant filled with autologous iliac crest bone graft.

Zausinger et al suggested possible benefit from combining a surgical approach with stereotactic radiosurgery[91] ; however, the value of this approach remains to be determined.

A posterior approach with no formal debridement has been described as a potential alternative to an anterior approach with aggressive debridement for the treatment of nontuberculous pyogenic spinal infection. A systematic review and meta-analysis by Elmajee et al found the posterior approach to be capable of yielding successful infection resolution, improved pain scores, and better neurologic outcomes but noted the need for larger series with longer follow-up periods.[94]

Significant postoperative discomfort limits activity for several days in most patients. A morphine patient-controlled analgesia (PCA) pump usually is employed during the first 36-48 hours.

To allow early patient mobilization postoperatively, patients are braced with an appropriate molded orthosis for a variable period, and a physical therapist is consulted.

The antibiotics should be adjusted according to the culture results.

Nursing care should include frequent repositioning, vigorous pulmonary toilet, and deep venous thrombosis (DVT) prophylaxis.

Long-term antibiotic treatment may, in itself, lead to complications such as cranial nerve (CN) VIII and renal toxicity, skin rashes, and other sequelae associated with specific antimicrobials.

During the postoperative period, patients with neurologic deficits are prone to multiple complications, including pressure injuries, pulmonary problems, DVT, and urinary sepsis.

Several studies have demonstrated that patients who are immunocompromised (eg, because of diabetes, rheumatoid arthritis [RA], chemotherapy, long-term steroid or narcotic use, or chronic smoking) have an increased incidence of wound healing problems and other complications. 

Severely impaired patients with limited mobility are at risk for developing skin decubitus injuries.

Ealy mobilization with a program of physical therapy is beneficial, reducing the risk of pulmonary and thromboembolic complications. To facilitate early patient mobilization, patients can be braced with an appropriate molded orthosis.

Several studies have shown that preincisional antimicrobial prophylaxis administration and use of postoperative antibiotics for 24 hour reduce the rate of SSI after spinal surgery.[95, 38] Prolonged (>48 hr) administration of antimicrobial prophylaxis postoperatively does not seem to be beneficial. 

A multidisciplinary team approach, including participation of an internist, an infectious disease specialist, a neurosurgeon, and a physical therapist, is beneficial.

Once correct treatment is implemented, patients require neurologic monitoring to exclude progressive neurologic deterioration. Home health care may help provide parenteral antibiotics, which typically are given until the infection resolves. Rehabilitation for any residual neurologic deficit may be necessary. This would include restrengthening programs and ambulation retraining.

In addition, follow-up laboratory and radiologic studies are necessary. A falling ESR is consistent with successful treatment. Decreases in serum C-reactive protein (CRP) have been shown to be more sensitive than the ESR. Serial radiographic studies are needed to detect bony collapse or deformity.

In 2015, the Infectious Diseases Society of America (IDSA) published clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis (NVO) in adults.[59]  

Recommendations pertaining to diagnosis included the following:

• NVO is typically diagnosed in the setting of recalcitrant back pain unresponsive to conservative measures and elevated inflammatory markers with or without fever
• Plain radiographs of the spine are not sensitive for the early diagnosis of NVO
• Magnetic resonance imaging (MRI) of the spine is often required to establish the diagnosis
• Except in septic patients or patients with neurologic compromise, empiric antimicrobial therapy should be withheld, when possible, until a microbiologic diagnosis is confirmed
• An image-guided or intraoperative aspiration or biopsy of a disc space or vertebral endplate sample submitted for microbiologic and pathologic examination often establishes the microbiologic or pathologic diagnosis of NVO
• NVO is commonly monomicrobial and most frequently due to  Staphylococcus aureus
• Clinicians should suspect the diagnosis of NVO in patients with new or worsening back or neck pain and fever
• Clinicians should suspect the diagnosis of NVO in patients with new or worsening back or neck pain and elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
• Clinicians should suspect the diagnosis of NVO in patients with new or worsening back or neck pain and bloodstream infection or infective endocarditis
• Clinicians may consider the diagnosis of NVO in patients who present with fever and new neurologic symptoms with or without back pain
• Clinicians may consider the diagnosis of NVO in patients who present with new localized neck or back pain, following a recent episode of  S aureus bloodstream infection
• A pertinent medical and motor/sensory neurologic examination is recommended in patients with suspected NVO
• Obtain bacterial (aerobic and anaerobic) blood cultures (2 sets) and baseline ESR and CRP in all patients with suspected NVO
• A spine MRI is recommended in patients with suspected NVO
• A combination spine gallium/technetium-99m bone scan is recommended, or a computed tomography (CT) scan or a positron emission tomography (PET) scan, in patients with suspected NVO when MRI cannot be obtained (eg, implantable cardiac devices, cochlear implants, claustrophobia, or unavailability)
• Obtain blood cultures and serologic tests for  Brucella species in patients with subacute NVO residing in endemic areas for brucellosis
• Obtain fungal blood cultures in patients with suspected NVO and at risk for fungal infection (epidemiologic risk or host risk factors)
• Perform a purified protein derivative (PPD) test or obtain an interferon gamma release assay in patients with subacute NVO and at risk for  Mycobacterium tuberculosis NVO (ie, originating or residing in endemic regions or having risk factors)
• In patients with suspected NVO, evaluation by an infectious disease specialist and a spine surgeon may be considered
• An image-guided aspiration biopsy is recommended in patients with suspected NVO (on the basis of clinical, laboratory, and imaging studies) when a microbiologic diagnosis for a known associated organism ( S aureus,  S lugdunensis, and  Brucella species) has not been established by blood cultures or serologic tests
• Recommend against performing an image-guided aspiration biopsy in patients with  S aureus,  S lugdunensis, or  Brucella species bloodstream infection suspected of having NVO on the basis of clinical, laboratory, and imaging studies
• Advise against performing an image-guided aspiration biopsy in patients with suspected subacute NVO (high endemic setting) and strongly positive  Brucella serology

Treatment recommendations included the following:

• In patients with neurologic compromise with or without impending sepsis or hemodynamic instability, immediate surgical intervention and initiation of empiric antimicrobial therapy are recommended
• In patients with normal and stable neurologic examination and stable hemodynamics, hold empiric antimicrobial therapy until a microbiologic diagnosis is established
• In patients with hemodynamic instability, sepsis, septic shock, or progressive or severe neurologic symptoms, initiate empiric antimicrobial therapy in conjunction with an attempt to establish a microbiologic diagnosis
• A total duration of 6 weeks of parenteral or highly bioavailable oral antimicrobial therapy is recommended for most patients with bacterial NVO
• A total duration of 3 months of antimicrobial therapy is recommended for most patients with NVO due to  Brucella species
• Surgical intervention is recommended in patients with progressive neurologic deficits, progressive deformity, and spinal instability with or without pain despite adequate antimicrobial therapy
• Surgical debridement with or without stabilization is recommended in patients with persistent or recurrent bloodstream infection (without alternative source) or worsening pain despite appropriate medical therapy (weak, low)
• Recommend against surgical debridement and/or stabilization in patients who have worsening bony imaging findings at 4-6 weeks in the setting of improvement in clinical symptoms, physical examination, and inflammatory markers