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Vertebral osteomyelitis, also referred to as disk-space infection, septic diskitis, spondylodiskitis, or spinal osteomyelitis, is the most common manifestation of hematogenous bone infection in adults. This designation reflects a pathogenic process leading to involvement of the adjacent vertebrae and the corresponding intervertebral disk. In adults, the disk is avascular. Microorganisms invade via the segmental arterial circulation in adjacent endplates and then spread into the disk. Alternative routes of infection are retrograde seeding through the prevertebral venous plexus and direct inoculation during spinal surgery, epidural infiltration, or trauma. In the setting of implant surgery, microorganisms are inoculated either during the procedure or, if wound healing is impaired, in the early postoperative period.
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Vertebral osteomyelitis occurs more often in male than in female patients (ratio, 1.5:1). Between 1995 and 2008, the incidence rate increased from 2.2 to 5.8 cases/100,000 person-years. There is a clear age-dependent increase from 0.3 case/100,000 at ages <20 years to 6.5 cases/100,000 at ages >70 years. The observed increase in reported cases during the past two decades may reflect improvements in diagnosis resulting from the broad availability of MRI technology. In addition, the fraction of cases of vertebral osteomyelitis acquired in association with health care is increasing as a consequence of comorbidity and the rising number of invasive interventions.
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Vertebral osteomyelitis is typically classified as pyogenic or nonpyogenic. However, this distinction is arbitrary: in “nonpyogenic” cases (tuberculous, brucellar), macroscopic pus formation (caseous necrosis, abscess) is quite common. A more accurate scheme is to classify cases as acute or subacute/chronic. Whereas the microbiologic spectrum of acute cases is similar in different parts of the world, the spectrum of subacute/chronic cases varies according to the geographic region. The great majority of cases are monomicrobial in etiology. Of episodes of acute vertebral osteomyelitis, 40–50% are caused by Staphylococcus aureus, 12% by streptococci, and 20% by gram-negative bacilli—mainly Escherichia coli (9%) and Pseudomonas aeruginosa (6%). Subacute vertebral osteomyelitis is typically caused by Mycobacterium tuberculosis or Brucella species in regions where these microorganisms are endemic. Osteomyelitis due to viridans streptococci also has a subacute presentation; these infections most often occur as secondary foci in patients with endocarditis. In vertebral osteomyelitis due to Candida species, the diagnosis is often delayed by several weeks; this etiology should be suspected in IV drug users who do not use sterile paraphernalia. In implant-associated spinal osteomyelitis, coagulase-negative staphylococci and P. acnes—which, in the absence of an implant, are generally considered contaminants—typically cause low-grade (chronic) infections. As an exception, coagulase-negative staphylococci can cause native spinal osteomyelitis in cases of prolonged bacteremia (e.g., in patients with infected pacemaker electrodes or implanted vascular catheters that are not promptly removed).
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CLINICAL MANIFESTATIONS
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The signs and symptoms of vertebral osteomyelitis are nonspecific. Only about half of patients develop fever >38°C (>100.4°F), perhaps because patients frequently use analgesic drugs. Back pain is the leading initial symptom (>85% of cases). The location of the pain corresponds to the site of infection: the cervical spine in ~10% of cases, the thoracic spine in 30%, and the lumbar spine in 60%. One exception is involvement at the thoracic level in two-thirds of cases of tuberculous osteomyelitis and at the lumbar level in only one-third. This difference is due to direct mycobacterial spread via pleural or mediastinal lymph nodes in pulmonary tuberculosis.
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Neurologic deficits, such as radiculopathy, weakness, or sensory loss, are observed in about one-third of cases of vertebral osteomyelitis. In brucellar vertebral osteomyelitis, neurologic impairment is less common; in tuberculous osteomyelitis, it is about twice as common as in cases of other etiologies. Neurologic signs and symptoms are caused mostly by spinal epidural abscess. This complication starts with severe localized back pain and progresses to radicular pain, reflex changes, sensory abnormalities, motor weakness, bowel and bladder dysfunction, and paralysis.
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A primary focus should always be sought but is found in only half of cases. Overall, endocarditis is identified in ~10% of patients. In osteomyelitis caused by viridans streptococci, endocarditis is the source in about half of patients.
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Implant-associated spinal osteomyelitis can present as either early- or late-onset infection. Early-onset infection is diagnosed within 30 days after implant placement. S. aureus is the most common pathogen. Wound healing impairment and fever are the leading findings. Late-onset infection is diagnosed beyond 30 days after surgery, with low-virulence organisms such as coagulase-negative staphylococci or P. acnes as typical infecting agents. Fever is rare. One-quarter of patients have a sinus tract. Because of the delayed course and the lack of classic signs of infection, rapid diagnosis requires a high degree of suspicion.
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Leukocytosis and neutrophilia have low levels of diagnostic sensitivity (only 65 and 40%, respectively). In contrast, an increased erythrocyte sedimentation rate or C-reactive protein (CRP) level has been reported in 98 and 100% of cases, respectively; thus, these tests are helpful in excluding vertebral osteomyelitis. The fraction of blood cultures that yield positive results depends heavily on whether the patient has been pretreated with antibiotics; across studies, the range is from 30 to 78%. In view of this low rate of positive blood culture after antibiotic treatment, such therapy should be withheld until microbial growth is proven unless the patient has sepsis syndrome. In patients with negative blood cultures, CT-guided or open biopsy is needed. Whether a CT-guided biopsy with a negative result is repeated or followed by open biopsy depends on the experience of personnel at the specific center. Bone samples should be cultured for aerobic, anaerobic, and fungal agents, with a portion of the sample sent for histopathologic study. In cases with a subacute/chronic presentation, a suggestive history, or a granuloma detected during histopathologic analysis, mycobacteria and brucellae also should be sought. When blood and tissue cultures are negative despite suggestive histopathology, broad-range polymerase chain reaction analysis of biopsy specimens or aspirated pus should be considered. This technique allows detection of unusual pathogens such as Tropheryma whipplei.
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Given that signs and symptoms of osteomyelitis are nonspecific, the clinical differential diagnosis of febrile back pain is broad, including pyelonephritis, pancreatitis, and viral syndromes. In addition, multiple noninfectious pathologies of the vertebral column, such as osteoporotic fracture, seronegative spondylitis (ankylosing spondylitis, psoriasis, reactive arthritis, enteropathic arthritis), and spinal stenosis must be considered.
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Imaging procedures are the most important tools not only for the diagnosis of vertebral osteomyelitis but also for the detection of pyogenic complications and alternative conditions (e.g., bone metastases or osteoporotic fractures). Plain radiography is a reasonable first step in evaluating patients without neurologic symptoms and may reveal an alternative diagnosis. Because of its low sensitivity, plain radiography generally is not helpful in acute osteomyelitis, but it can be useful in subacute or chronic cases. The gold standard is MRI, which should be performed expeditiously in patients with neurologic impairment in order to rule out a herniated disk or to detect pyogenic complications in a timely manner. Even if the pathologic findings on MRI suggest vertebral osteomyelitis, alternative diagnoses should be considered, especially when blood cultures are negative. The most common alternative diagnosis is erosive osteochondrosis. Septic bone necrosis, gouty spondylodiskitis, and erosive diskovertebral lesions (Andersson lesions) in ankylosing spondylitis may likewise mimic vertebral osteomyelitis. CT is less sensitive than MRI but may be helpful in guiding a percutaneous biopsy. In the future, positron-emission tomography (PET) with 18F-fluorodeoxyglucose, which has a high degree of diagnostic accuracy, may be an alternative imaging procedure when MRI is contraindicated. 18F-fluorodeoxyglucose PET should be considered for patients with implants and patients in whom several foci are suspected.
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TREATMENT Vertebral Osteomyelitis
The aims of therapy for vertebral osteomyelitis are (1) elimination of the pathogen(s), (2) protection from further bone loss, (3) relief of back pain, (4) prevention of complications, and (5) stabilization, if needed.
Table 126-1 summarizes suggested antimicrobial regimens for infections attributable to the most common etiologic agents. For optimal antimicrobial therapy, identification of the infecting agent is required. Therefore, in patients without sepsis syndrome, antibiotics should not be administered until the pathogen is identified in a blood culture, a bone biopsy, or an aspirated pus collection. Traditionally, bone infections are at least initially treated by the IV route. Unfortunately, relevant controlled trials are lacking, and the preference for the IV route is not evidence based. There are no good arguments for the assumption that IV therapy is superior to oral administration if the following requirements are met: (1) optimal antibiotic spectrum, (2) excellent bioavailability of the oral drug, (3) clinical studies confirming efficacy of the oral drug, (4) normal intestinal function, and (5) no vomiting. However, a short initial course of parenteral therapy with a β-lactam antibiotic may lower the risk of emergence of fluoroquinolone resistance, especially if P. aeruginosa infection is treated with ciprofloxacin or staphylococcal infection with the combination of a fluoroquinolone plus rifampin. These suggestions are based on observational studies and expert opinion. A recent randomized, controlled trial showed that 6 weeks of antibiotic treatment is not inferior to a 12-week course in patients with pyogenic vertebral osteomyelitis. The cure rate was 90.9% in both groups 1 year after therapy. Thus, prolonged antibiotic therapy is required only for patients with undrained abscesses and for patients with spinal implants. Treatment efficacy should be regularly monitored through inquiries about signs and symptoms (fever, pain) and assessment for signs of inflammation (elevated CRP concentrations). Follow-up MRI is appropriate only for patients with pyogenic complications, since the correlation between clinical healing and improvement on MRI is very poor.
Surgical treatment generally is not needed in acute hematogenous vertebral osteomyelitis. However, it is always necessary in implant-associated spinal infection. Early infections (those occurring up to 30 days after internal stabilization) can be cured with debridement, implant retention, and a 3-month course of antibiotics (Table 126-2). In contrast, in late infection with a duration of >30 days, implant removal and a 6-week course of antibiotics (Table 126-1) are required for complete elimination of the infection. If implants cannot be removed, oral suppressive long-term treatment should follow the initial course of IV antibiotics. The optimal duration of suppressive therapy is unknown. However, if antibiotic therapy is discontinued after, for example, 1 year, close clinical and laboratory (CRP) follow-up is needed.
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Complications should be suspected when there is persistent pain, a persistently increased CRP level, and new-onset or persistent neurologic impairment. In cases of persistent pain with or without signs of inflammation, paravertebral, epidural, or psoas abscesses (Fig. 126-1) must be sought. Epidural abscesses occur in 15–20% of cases. This complication is more common in the cervical column (30%) than in the lumbar spine (12%). Persistent pain despite normalization of CRP values indicates mechanical complications such as severe osteonecrosis or spinal instability. These patients require a consult with an experienced orthopedic surgeon.
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GLOBAL CONSIDERATIONS
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The incidence rate of acute vertebral osteomyelitis is similar in different regions of the world. In contrast, subacute/chronic vertebral osteomyelitis predominates in defined regions. Cases attributable to brucellosis predominate in endemic areas such as the Middle East, Africa, Central and South America, and the Indian subcontinent. Tuberculosis is an especially frequent cause in Africa and Asia (India, Indonesia, China), where more than two-thirds of the global tuberculosis burden is reported. Thus, specific diagnostic tests are needed in patients either living in or having traveled to these regions.