Introduction

Background
Diskitis is an inflammation of the vertebral disk space often related to infection. Infection of the disk space must be considered with vertebral osteomyelitis, as these conditions are almost always present together and share much of the same pathophysiology, symptoms, and treatment. Although diskitis and associated vertebral osteomyelitis are uncommon conditions, they are often the causes of debilitating neurologic injury. Unfortunately, morbidity can be exacerbated by a delay in diagnosis and treatment of this condition. The lumbar region is most commonly affected, followed by the cervical spine and, lastly, the thoracic spine.1,2,3,4,5 See images below.

Axial CT scan in a patient with diskitis demonstrates extensive destruction of the vertebral endplate. Note the preservation of the posterior elements, including facet joints, lamina, and spinous process. This is characteristic for pyogenic diskitis and less common in tuberculosis (Pott disease).

Sagittal T1-weighted MRI of the lumbar spine in a 74-year-old man, revealing diskitis of the L4-L5 disk space. Note extensive destruction of the endplates of the adjacent vertebral bodies. No compression of the thecal sac is present, which is an important consideration when contemplating surgical intervention.

Contrast-enhanced sagittal T1-weighted MRI image in a 55-year-old woman shows thoracic diskitis with an associated epidural abscess and spinal cord compression. Because of the significant cord compression, this patient underwent surgical decompression.

Trajectory of a needle in a biopsy of the infected disk space guided by CT scan. Care is taken to avoid the thecal sac and nerve roots.

Recent studies Sharma et al reported on the severe complication of diskitis following diskography. They found that based on the available clinical evidence, IV or intradiskal antibiotics during diskography have not been conclusively shown to decrease the rate of diskitis over sterile technique alone. Animal model research supports prophylactic antibiotic use when used before iatrogenic inoculation of intervertebral disks. Both single- and double-needle techniques when used with stylettes are superior to nonstyletted techniques, according to the authors.6 Maus et al studied procalcitonin (PCT) as a diagnostic tool and monitoring parameter for spondylodiskitis and for discrimination between bacterial infection and aseptic inflammation of the spine. A total of 17 patients with spondylodiskitis and 18 patients with disk herniation used as controls were included in this study. The findings showed, however, that PCT is not useful as diagnostic tool or monitoring parameter for spondylodiskitis, nor was it useful for the discrimination between a bacterial infection and an aseptic inflammation of the spine.7 Karadimas et al retrospectively analyzed the outcome of a large series of patients treated either nonoperatively or surgically for spondylodiskitis. The patients were divided into 3 groups: (A) 70 patients who had nonoperative treatment, (B) 56 patients who underwent posterior decompression alone, and (C) 37 patients who underwent decompression and stabilization. At 12-month follow-up, nonoperative treatment (group A) had failed in 8/70 patients. In 24 of 56 group B patients and in 6

of 37 group C patients, reoperation was necessary. Group A patients had no neurologic symptoms; in group B, 11 had neurologic deficits, and surgery was beneficial for 5 of them; and in group C, 11 patients had altered neurologic deficits.8

Pathophysiology
An infection does not ordinarily originate in the vertebra or disk space, but rather, it spreads there from other sites via the bloodstream. Spinal arteries form 2 lateral anastomotic chains and 1 median anastomotic chain along the posterior surface of the vertebral bodies. The spinal arteries are the origins of the periosteal arteries, which in turn give rise to metaphyseal arteries. In the child, anastomoses between metaphyseal arteries are made by the intermetaphyseal arteries; however, in the adult, these intermetaphyseal arteries degenerate, causing direct diffusion from the adjacent endplate to be the only source of nutrients for the disk. Septic emboli travelling through this arterial system enter the metaphyseal arteries, which have become end arteries in the adult, causing a large area of infarction. Infarction of the vertebral endplates is followed by localized infection that subsequently spreads through the vertebral body and into the poorly vascularized disk space. Infection can then spread to the epidural space or paraspinal soft tissues. The other anastomotic vascular system of the spine is the venous system. The venous system of the spine, like the arterial system, also forms an anastomotic plexus (ie, Batson plexus) in the epidural space. This plexus drains each segmental level and is continuous with the pelvic veins. Retrograde flow through this plexus during periods of high intra-abdominal pressure has been postulated to allow the spread of infection from the pelvic organs. Support for this hypothesis comes from the observation that pelvic disease is one of the most common primary sites of infection in patients with diskitis. Other authors take issue with this hypothesis, citing animal studies that show retrograde flow through the epidural venous plexus only at extremely high intraabdominal pressures that are not physiologic.

Frequency
United States

Incidence ranges from 1 in 100,000 population to 1 in 250,000 population.

International

In other developed nations, the incidence of diskitis is similar to that in the United States; however, in less developed nations, infectious diskitis is much more common. In some areas of Africa, it has been reported that 11% of all patients seen for back pain were diagnosed with diskitis.

Mortality/Morbidity
Mortality associated with diskitis occurs from the spread of infection, either through the nervous system or through other organs. Mortality has been reported to be 2-12%.

Race
No specific racial predilection has been noted.

Sex
The predominance of diskitis in males is more pronounced in adults, with male-to-female ratios ranging from 2:1 to as high as 5:1. Childhood diskitis has a slight male prevalence, with a male-tofemale ratio of 1.4:1.

Age

A bimodal distribution of ages occurs with diskitis. Childhood diskitis affects patients with a mean age of 7 years. The incidence of diskitis then decreases until middle age, when a second peak in incidence is observed at approximately 50 years of age. Some authors argue that childhood diskitis is a separate disease entity and should be considered independently.

Clinical
History

Unfortunately, adult diskitis has a slow, insidious onset, which can cause diagnosis to be delayed for months. Neck or back pain with localized tenderness is the initial presenting complaint. Movement exacerbates these symptoms, which are not alleviated with conservative treatment (eg, analgesics, bed rest). o In patients who are chronically ill, a high incidence of epidural extension of the infection exists, causing lower extremity weakness or plegia. Fever, chills, weight loss, and symptoms of systemic disease may be present but are not common. In postoperative patients, symptoms usually begin days to weeks after surgery.

Symptoms are similar to those experienced by patients with spontaneous diskitis, which consists of pain without neurologic abnormality. Limited movement and localized tenderness also occur; however, superficial signs of infection are rare (only 10% of cases). Diagnosis is rarely delayed in postoperative patients, which is the main reason that neurologic deficit is uncommon in these cases. The disease has a more acute course in children. A sudden onset of back pain, refusal to walk, and irritability are the most common symptoms. Fever is often present, accompanied by local tenderness and limited back motion.

Physical
Localized tenderness over the involved area with concomitant paraspinal muscle spasm is the most common physical sign. If the cervical or lumbar segments are involved, restricted mobility secondary to pain occurs. Reported rates of neurologic deficit (eg, radiculopathy, myelopathy) vary widely from 2% to 70%. Cervical disease is associated with a much higher rate of neurologic deficit.

Causes

Diskitis is thought to spread to the involved intervertebral disk via hematogenous spread of a systemic infection (eg, urinary tract infection [UTI]). Many sites of origin have been implicated, but UTI, pneumonia, and soft-tissue infection seem to be the most common. Direct trauma has not been conclusively shown to be related to diskitis. Intravenous drug use with contaminated syringes offers direct access to the bloodstream for a variety of organisms. Often, no other site of infection is discovered. Staphylococcus aureus is the organism most commonly found; however, Escherichia coli and Proteus species are more common in patients with UTIs. Pseudomonas aeruginosa and Klebsiella species are other gram-negative organisms observed in intravenous drug abusers, although they are not seen as commonly as S aureus. Not surprisingly, medical conditions that predispose patients to infections elsewhere in the body are associated with diskitis. Diabetes, AIDS, steroid use, cancer, and chronic renal insufficiency are common comorbidities.1 Although rare, infection of the disk space can also occur following surgical intervention at the site. The rate of infection following anterior cervical diskectomy has been quoted at 0.5% of cases. The rate of infection for lumbar diskectomy is half of that. In such cases,

infection is transmitted through direct inoculation of the operative site. As in spontaneous diskitis, the most common organism is S aureus, but Staphylococcus epidermidis and Streptococcus species also should be considered. Childhood diskitis has not been consistently associated with an initial causative infection elsewhere in the body. S aureus is the most common organism found.

Differential Diagnoses
Osteomyelitis Rheumatoid Spondylitis Spinal Tumors

Other Problems to Be Considered

Spinal epidural abscess Pyelonephritis Rheumatoid arthritis

Workup
Laboratory Studies

Hematology o Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are

o o o

the most consistent laboratory abnormalities seen in cases of diskitis. The mean ESR for patients with diskitis is 85-95 mm per hour. ESR utility can be extended by serial measurements during treatment. A 50% decline in ESR can usually be expected with successful treatment, and ESR often continues to decline after treatment. Frequently, ESR may not return to normal levels despite adequate therapy.

Leukocytosis is often present in systemic disease but is frequently absent in diskitis cases. Diskitis is generally accompanied by a normal peripheral white blood cell (WBC) count if the primary site of infection has been treated. Microbiology o Blood cultures must be obtained on a frequent basis for any patient suspected of

o o

harboring an infected disk. Appropriate therapy may be instituted for positive blood cultures without the need for invasive tests. Unfortunately, blood cultures are positive in only one third to one half of diskitis

cases. Sputum and urine cultures are necessary to locate any other sources of infection, including respiratory and genitourinary sites.

Imaging Studies

Plain radiography o Although radiographic films of the spine can be very useful in diagnosing diskitis,

abnormalities are visible only after several weeks following the onset of disease. The most common early finding on plain films is disk-space narrowing, followed by irregularities and erosion of the adjacent endplates and calcification of the anulus around the affected disk.

As osteomyelitis progresses, bone density decreases, with loss of the normal

trabeculation of the vertebra. If bone destruction continues, subluxation (with possible instability of the spine) becomes evident. Nuclear medicine o Gallium-67 and technetium-99m have been utilized in the detection of diskitis with similar results. Radionuclide scanning has demonstrated a high degree of sensitivity shortly after the onset of symptoms. Diffuse initial uptake is followed by more focal uptake on delayed scans. Technetium-99m has been recommended more often because of its lower cost and smaller radiation dose. Because of the availability and sensitivity of other tests, radionuclide scans may be most useful in the workup of patients with fever of unknown origin. Indium-111 WBC scintigraphy has been shown to have a low sensitivity for diskitis and is not the test of choice.

o o
CT scan

o o

CT scanning has the ability to detect diskitis earlier than plain radiographs. Findings include hypodensity of the intervertebral disk and destruction of the adjacent endplate and bone, as seen in the image below, with edematous surrounding tissues.

Axial CT scan in a patient with diskitis demonstrates extensive destruction of the vertebral endplate. Note the preservation of the posterior elements, including facet joints, lamina, and spinous process. This is characteristic for pyogenic diskitis and less common in tuberculosis (Pott disease).

o o

Organisms at the affected site can also produce a gas that is easily detected on CT scans. The advantage of CT scans over radiographs is that associated paraspinal disease can also be detected, especially when combined with intravenous contrast or myelography. Use of CT scanning can supplement magnetic resonance imaging (MRI), as it is better at distinguishing between bone and soft tissue than MRI. CT can help monitor successful treatment, which is accompanied by increased bone density and sclerosis.

o o
MRI

The most sensitive and specific test for diskitis is MRI. T1-weighted images, as seen in the image below, show narrowing of the disk space and low signals consistent with edema in the marrow of adjacent vertebral bodies. T2-weighted

images show increased signals in both the disk space and the surrounding vertebral bodies.

Sagittal T1-weighted MRI of the lumbar spine in a 74-yearold man, revealing diskitis of the L4-L5 disk space. Note extensive destruction of the endplates of the adjacent vertebral bodies. No compression of the thecal sac is present, which is an important consideration when contemplating surgical intervention.

o o o

MRI is very useful in helping distinguish between infectious diskitis, neoplasia, and tuberculosis. Disk space involvement directs attention to infection, as it only is involved late in tuberculosis and very rarely in neoplasia. With the use of intravenous contrast, as seen in the image below, MRI, like CT, can detect paraspinal disease (eg, paraspinal phlegmon, epidural abscess).

Contrast-enhanced sagittal T1-weighted MRI image in a 55year-old woman shows thoracic diskitis with an associated epidural abscess and spinal cord compression. Because of the significant cord compression, this patient underwent surgical decompression.

A large amount of paraspinal soft-tissue swelling and a psoas abscess are often associated with spinal tuberculosis.

Bone scans are not specific for infection over inflammation; therefore, they are ineffective in postoperative patients.

Other Tests

Echocardiography can detect bacterial endocarditis, which is a common source of diskitis and embolic infection throughout the body.

Procedures

Needle biopsy o Needle or trocar placement into the infected area is a minimally invasive test used to obtain histologic confirmation of the disease and tissue samples for culture. Yield and safety of the procedure are maximized by the use of CT scanning for guidance (see image below).

Trajectory of a needle in a biopsy of the infected disk space guided by CT scan. Care is taken to avoid the thecal sac and nerve roots.

As in blood cultures, positive tissue cultures occur in only half of biopsies,

especially if antibiotic therapy has already been initiated. In such cases, needle biopsy can be repeated or the patient can be referred for open surgical biopsy. Surgical biopsy o Open biopsy has been found in some studies to have the highest yield in terms of

o o

positive cultures and diagnosis confirmation. Open biopsy is the most invasive test. While some surgeons prefer to combine open biopsy with surgical debridement, no difference has been found between antibiotics and debridement when compared with antibiotics alone in cases of early diskitis.

Histologic Findings
The histologic findings of diskitis 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.

Treatment

Medical Care

Antibiotic treatment must be tailored to the isolated organism and any other sites of infection. o Broad-spectrum antibiotics must be used if no organism is isolated; however, this is very rare, and other disease processes (eg, spinal tuberculosis) must be considered in the face of persistently negative cultures. Parenteral treatment is usually administered for 6-8 weeks. Before parenteral therapy is discontinued, the ESR should have dropped by one half to one third, the patient should have no pain on ambulation, and there should be no neurologic deficits.1,3 The use of oral antibiotics following intravenous treatment has not been shown to be of added benefit. Any laboratory or clinical sign of persistent infection should prompt another

o o

biopsy and continued antibiotic therapy. Immobilization is necessary, especially in the initial stages of the disease. o Two weeks of bed rest should be followed by external immobilization with a brace

o o o

when the patient gets out of bed. Any pain on ambulation is an indication for continued bed rest. The goal of immobilization is to provide the opportunity for the affected vertebrae to fuse in an anatomically aligned position. Generally, bracing is used for 3-6 months following initiation of treatment;

however, even with the use of appropriate antibiotics and bracing, collapse of the vertebral segments and kyphos formation may occur. Pain control is an important adjunct to antibiotics and immobilization.2

Surgical Care
Indications for surgery beyond open biopsy include neurologic deficit, spinal deformity, disease progression, noncompliance, and antibiotic toxicity. The goal of surgery is to remove diseased tissue, decompress neural structures, and ensure spinal stability. Although in most cases the vertebrae fuse spontaneously following diskitis and osteomyelitis, operative fusion can be a useful adjunct by allowing earlier mobilization of the patient. Despite early concerns, use of a fusion plug and metallic instrumentation in an infected field has not been shown to impede successful treatment.

Consultations

Infectious disease Neurosurgery Orthopedic spine surgery

Diet
No particular diet has been shown to have a clinical benefit in patients with diskitis.

Activity
Many authors believe that 2 weeks of bed rest with initial treatment helps prevent the development of a kyphotic deformity. Use of an orthotic brace to help stabilize the spine while spontaneous fusion takes place is recommended for 3-6 months. Ambulation is recommended only if the patient has neither pain nor radiographic signs of instability.

Medication
Parenteral narrow-spectrum antibiotics should be prescribed according to the organism isolated. If cultures are consistently negative, administer broad-spectrum antibiotics for several weeks.

Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Vancomycin (Lyphocin, Vancocin, Vancoled)

Potent antibiotic that is directed against gram-positive organisms and is active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins or cephalosporins or who have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose is drawn and a half an hour prior to the next dose. Use CrCl to adjust the dosage in patients diagnosed with renal impairment. Used in conjunction with gentamicin for prophylaxis in patients who are allergic to penicillin and are undergoing gastrointestinal or genitourinary procedures.

Adult

Dosing Interactions Contraindications Precautions

500 mg/d to 2 g/d IV divided tid/qid for 7-10 d

Pediatric

40 mg/kg/d IV divided tid/qid for 7-10 d

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Gentamicin (Garamycin, Gentacidin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Not the drug of choice (DOC). Consider if penicillins or other less toxic drugs are contraindicated, in mixed infections caused by susceptible staphylococci and gram-negative organisms, or when clinically indicated.

Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM.

Adult

Dosing Interactions Contraindications Precautions

Serious infections and normal renal function: 3 mg/kg/dose IV q8h Loading dose and maintenance dose: 1.0-2.5 mg/kg IV and 1.0-1.5 mg/kg IV, respectively, q8h Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM q6-8h Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion
Pediatric

<5 years: 2.5 mg/kg/dose IV/IM q8h >5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6.0-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Nafcillin (Unipen, Nallpen, Nafcil)

Initial therapy for suspected penicillin-Gresistant streptococcal or staphylococcal infections. Use parenteral therapy initially for severe infections. Change to oral therapy as condition warrants. Due to thrombophlebitis, particularly in the elderly, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated.

Adult

Dosing Interactions Contraindications Precautions

250 mg to 1 g PO q4-6h Alternatively, 500 mg to 1 g IV/IM q4-6h

Pediatric

0-4 kg (neonates): 10 mg/kg IM bid 4-40 kg: 25 mg/kg IM bid or 50 mg/kg/d PO divided qid Alternatively, 100-200 mg/kg/d IV/IM in 4-6 divided doses

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Ceftazidime (Tazidime, Tazicef, Ceptaz, Fortaz)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Adult

Dosing Interactions Contraindications Precautions

250-500 mg to 2 g IV/IM q8-12h

Pediatric

Neonates: 30 mg/kg IV q12h Infants and children: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d Adolescents: Administer as in adults

Follow-up
Further Inpatient Care

Once the correct treatment is implemented, monitor patients to rule out progressive neurologic deficit.

Further Outpatient Care

Laboratory analysis o A falling ESR is consistent with successful treatment. o Although ESR values should fall by at least one third to one half, rarely do they

return to preinfection levels. Reduction of CRP levels has been shown to be more sensitive in some studies

than ESR. Radiography o Serial radiographic examination is a necessity to detect bony collapse or

deformity. Successful treatment is accompanied by appropriate changes, including sclerosis of the endplates, on plain films and CT scans.

Nevertheless, radiographic findings are significantly slower than clinical response and cannot be used to assess eradication of infection.

Inpatient & Outpatient Medications

Parenteral antibiotics are a requirement, even for outpatients. Pain medications can be a useful adjunct, as they allow for increased mobilization.

Transfer

Transfer to an institution with neurosurgical or orthopedic spinal care is warranted for any patient demonstrating neurologic decline for decompression and possible stabilization.

Deterrence/Prevention

No specific deterrence is available for diskitis except treatment of the underlying disease (eg, diabetes, sepsis).

Complications

Neurologic deficits develop in 13-40% of patients, especially those with diabetes or other systemic illnesses. Long-term antibiotic therapy may lead to ototoxicity or renal toxicity.

Prognosis

Most patients are cured by a treatment protocol of antibiotics, either alone or in combination with surgery. Only 15% of patients experience permanent neurologic deficits. Recrudescence of infection occurs in 2-8% of patients.

Patient Education

The significance of antibiotic regimen compliance is the single most important factor in patient education. Incomplete treatment can lead to resistance with devastating results. The importance of orthotic brace compliance must also be stressed. Educate patients on early neurologic signs, and instruct patients to return for medical attention on detection of the slightest deficit.

Miscellaneous
Medicolegal Pitfalls

The most significant pitfall associated with diskitis is failure to diagnose an epidural abscess. A significant number of epidural abscess cases go undetected until serious neurologic decline has occurred. Neurologic deficit is sometimes thought to be caused by a vascular ischemic event rather than simple compression. In these cases, the prognosis for complete recovery is unfavorable once a serious deficit has occurred.