Section 19, Chapter 1: Infections of the Spine

Harold I. Salmons, Jeffrey Ta, Hamadi Murphy, Arjun Sebastian, Kris Radcliff, Alex Vaccaro

INTRODUCTION

Spinal infections involve pyogenic or granulomatous infections of the vertebral column, intervertebral discs, the dural sac or the epidural space. Infections of the spine can take the form of a primary infection of the spine or a spread of microorganisms originating from elsewhere in the body. Spinal infections can also develop postoperatively and most often develop secondary to direct inoculation of the wound. Regardless of the source of the infection, an infection of the spine should be quickly diagnosed in order to prevent structural instability or neurologic compromise. This chapter describes both primary and post-operative spinal infections. Epidemiology, risk factors, etiology, clinical presentation, diagnostic maneuvers, treatment options and prognoses will be explored.

SECTION I: PRIMARY SPINE INFECTIONS

Primary spinal infections are described as infections of the vertebrae that are not secondary to an operation. Such infections commonly originate from elsewhere in the body and spread to the spine and its musculoskeletal components. Pyogenic infections of the spine most frequently involve the lumbar spine (58%), followed by the thoracic (30%) and cervical (11%) regions. Gram-positive organisms such as Staphylococcus aureus and Streptococcus species are the most commonly isolated organisms in patients with pyogenic vertebral infections.¹

Pyogenic Infections of the Spine

Primary vertebral osteomyelitis and discitis

Epidemiology

Spine infections are rare infections that can involve the intervertebral disc space (discitis), the vertebral bones, the spinal canal or adjacent soft tissues. Discitis refers to an infection of the intervertebral disc in the spine. Vertebral osteomyelitis refers to an infection of the vertebral bones in the spine. Infection usually is caused by bacterial organisms, but can also be due to viral or fungal organisms. The most common primary spinal infection is pyogenic vertebral osteomyelitis. Vertebral osteomyelitis mostly occurs in adults, with the majority occurring in patients over 50 years old.²The disease may occur from infancy to old age, but has a predilection for the elderly.^2–11The incidence may be higher in younger patients that are intravenous drug abusers.¹²Vertebral osteomyelitis affects men approximately twice as much as women, but the reason for this is not fully understood.¹³ Vertebral osteomyelitis occurs at an incidence of approximately 2.2/100,000 per year.^5,14 That prevalence of this infection increases with age is possibly due to a number of factors: the increasing age of the population, increasing number of patients on renal replacement therapy, increasing number of patients with immunosuppressive medications and increasing rates of bacteremia due to intravascular devices and other forms of instrumentation.^13,15,16

Risk factors

Risk factors for infections of the spine involve conditions that weaken the patient’s immune system, such conditions include diabetes mellitus, use of immunosuppressant medications, cancer, HIV/AIDS, malnutrition, history of an organ transplant and intravenous drug abuse.

Etiology

Any condition that causes a bacteremia (even temporary bacteremia such as tooth brushing or venipuncture) may lead to hematogenous vertebral osteomyelitis. The most common sources are urinary tract infections and the transient bacteremia caused by genitourinary procedures.^5,17-21 Vertebral osteomyelitis may accompany diarrhea due to salmonellosis,²² otitis media,³ dental extraction,²³ infective endocarditis and hemodialysis.²⁴ Spine surgeries, penetrating wounds, chemonucleolysis or discogphaphy may directly inoculate the spine as well.^6,25-33

Pathogenesis

There are multiple ways that bacteria can spread into the vertebral column. Three major routes of spread are: (1) hematogenous spread from a distant infection, (2) direct inoculation from trauma, (3) direct inoculation following invasive spinal diagnostic procedures and from spinal surgery. Any condition that causes a bacteremia may lead to hematogenous vertebral osteomyelitis. Osteomyelitis following hematogenous spread of infection is the major mechanism by which adults and children contract vertebral osteomyelitis. Infection spreads into vertebral bodies by first seeding underneath vertebral end plates, which is followed by disc and nearby vertebrae involvement. The extent of this spreading is larger in pediatric spines due to their blood vessels extending into the intervertebral disc, permitting the direct spread of infection to the discs.³⁴ Many now believe that the sluggish flow, scarcity of valves and convolution of the arterial or venous supply leads to vertebral osteomyelitis in patients with bacteremia. Potential sources of hematogenous or contiguous spread of infection include the genitourinary tract, skin and soft tissue (via injection drug use), respiratory tract, infected IV catheter sites, postoperative wound infection, endocarditis and dental infection. In some cases the primary site of infection cannot be identified.³⁵

Since the vascular supply supplying the vertebrae usually bifurcate to supply two adjacent end plates of adjacent vertebrae, hematogenous vertebral osteomyelitis often causes bone destruction of adjacent vertebral bodies and their shared IV disc.³⁶ The lumbar vertebral bodies are most often involved, followed by thoracic and then cervical vertebral bodies.³⁷ Hematogenous sacral osteomyelitis is very rare. Sacral osteomyelitis most often occurs as a result of sacral pressure ulcers; however, it can also follow pelvic infection, trauma and surgeries.^38,39 Contiguous spread from adjacent tissues such as the aorta, esophagus or bowel have also been reported. Extension of infection posteriorly can lead to epidural abscess, subdural abscess or meningitis. Lateral extension of infection can lead to psoas, retroperitoneal, subphrenic, paravertebral, retropharyngeal and mediastinal abscesses as well. Epidural or paravertebral abscess development is most common in cases where the invading bacterium is gram-positive rather than gram-negative.⁴⁰ The spinous process, pedicles, odontoid process and facet joints can also be affected.⁴¹ Some patients present with septic facet joints and paraspinous muscle abscesses in the multifidus and longissimus muscles.

Clinical features

Back or neck pain is a common symptom of vertebral osteomyelitis. This pain may radiate to the abdomen, scrotum, leg, groin or perineum. The pain is often worse at night. Therefore, the pain does not resemble the behavior of the typical “mechanical” back pain which is worse with upright position and activity during the day. This atypical pain is usually localized to the affected anatomical area (e.g. cervical, thoracic, lumbar) unless there is multifocal infection. The pain is amplified by percussion to the affected area or physical activity. Pain may be absent in patients with Charcot spine or paraplegia. Neurologic changes such as radicular numbness and muscle weakness may be present in up to one third of patients.

Epidural abscesses may form as a result of posterior spread into the epidural space, and these can cause neurological abnormalities depending on several factors, including the severity of the abscess, the extent of stenosis, the anatomical region and the duration of time present. Epidural abscesses can therefore present with radiculopathy, motor weakness, sensory changes, paralysis or cauda equina syndrome.⁴² Epidural abscesses can also be asymptomatic.

Patients with lumbar psoas abscesses can present with lumbar plexopathy due to the neural compression. These patients may have weakness with hip flexion, knee extension, sensory abnormalities over the upper thigh and anterior knee, or other neurological abnormalities in the affected nerve distributions. Psoas abscesses can also be asymptomatic.

Diagnosis

Concern for vertebral osteomyelitis is warranted when patients present with new or worsening back or neck pain, particularly in combination with fever, and/ or presence of blood stream infection and/or endocarditis.^22,13 Further, clinicians should be suspicious of febrile patients presenting with new neurological symptoms (pain may or may not be present) and patients with new back or neck pain following a recent episode of S. aureus bacteremia.²² Back pain in patients with this diagnosis may respond to bed rest at first, leading to the incorrect assumption that non-infectious causes are present. Additionally, a history of degenerative spine disease may delay diagnosis.^13,22

Detecting likely organisms such as S. aureus via CT-guided biopsy of the area in question permits a conclusive diagnosis of vertebral osteomyelitis.⁴³ The diagnosis may be inferred without biopsy in cases of clinical and radiographic findings typical of vertebral osteomyelitis with likely pathogens. Disc space biopsy may be used in certain circumstances where a positive blood culture is detected. Elevated inflammatory markers and suggestive radiographic findings could also suggest the diagnosis when appropriate culture data is not present.

Clinical approach

As a part of a complete history and physical evaluation, patients should be examined thoroughly for neurologic symptoms and questioned about risk factors. Initial tests should include white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and blood cultures followed by magnetic resonance imaging (MRI) of the spine.⁴⁴ Neurological deficits and radiographic evidence of abscess with possible cord compression warrant surgical evaluation.

In the absence of conditions warranting urgent surgical management, patients with radiographic evidence of osteomyelitis should undergo a CT-guided needle biopsy of the affected bone and aspiration of the abscess if one is present.⁴⁴ Antibiotics should be withheld if possible to avoid contaminating the biopsy. However, in one retrospective study of 92 subjects with vertebral osteomyelitis, giving antibiotics prior to biopsy did not reduce the results of culture yields.⁴⁵ Cultures for bacteria, fungi and mycobacteria should be obtained as well. In the case of sepsis, empirical antibiotic therapy is acceptable, but otherwise antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed.²² It should be noted that a needle biopsy may not be necessary in patients with clinical and radiographic findings typical of vertebral osteomyelitis and positive blood cultures with a common pathogen. However, blood culture isolates do not always correlate with culture results from needle biopsy; therefore, needle biopsy should be considered in cases when an alternate source for the bacteremia is evident or suspected.⁴⁶ If repeat biopsy and initial blood cultures are negative, empirical therapy may follow. If this therapy does not result in objective clinical improvement in three to four weeks, another needle biopsy or preferably an open surgical biopsy should be performed. To rule out noncontiguous lesions, patients should undergo screening imaging of the entire spinal axis.

Treatment

Antimicrobial therapy without surgical intervention is warranted in patients presenting without progressive neurological symptoms. Those that do present with neurologic symptoms should be evaluated for surgery. If cultures are negative but vertebral osteomyelitis is highly suspected based on radiographic findings, empirical therapy initiation is warranted.²² Medications that are appropriate for treating vertebral osteomyelitis vary, and choice of antibiotic should be based on biopsy and culture results. To date, there have been no controlled studies that have compared antibiotic regimens in cases with vertebral osteomyelitis.

If culture/biopsy indicates a Staphylococcal species, in particular methicillin-susceptible Staphylococcus, it is recommended to treat with an anti-staphylococcal penicillin such as nafcillin or oxacillin or cefazolin.¹³ If the Staphylococcus is methicillin resistant or if the patient is allergic to beta-lactam antibiotics, beta-lactam desensitization or treatment with vancomycin is recommended. Ceftriaxone should not be used as an alternative to cefazolin or anti-staphylococcal penicillin in the absence of special circumstances, such as inability to give multiple daily IV doses.

If the bacterium is found to be of the Streptococcal species and if the streptococci is sensitive to penicillin, it is recommended to treat with either ceftriaxone or penicillin G. If the Streptococcus has intermediate susceptibility to ceftriaxone, then higher doses of penicillin may be used. Specialized in vitro testing through an infectious disease specialist may be necessary for patients with fully resistant streptococci. Empirical therapy targeting the common pathogens using is warranted for gram-negative bacteria.

To treat infection due to Propionibacterium acnes it is recommended to treat with penicillin or vancomycin.

Fungal vertebral osteomyelitis, particularly those of the Candida fungal organism are difficult to treat because the diagnosis is often delayed for weeks to months.^47,48 The infected bone is often poorly perfused, which limits both the delivery of antifungal drugs and the host’s own inflammatory response.⁴⁹ Furthermore, foreign material may be present as a result of procedures like median sternotomy.^47,48 Few data are available on the penetration of antifungal agents into bone.⁵⁰ Despite the treatment challenges for vertebral osteomyelitis due to fungal infections, treatment suggestions for osteomyelitis caused by fluconazole-susceptible Candida species such as C. albicans include oral fluconazole daily for 6 to 12 months or an IV echinocandin daily for at least two weeks followed by oral fluconazole for a total of 6 to 12 months.²⁵

Alternatively, a lipid formulation of amphotericin B, 3 to 5 mg/kg IV daily, can be administered for at least two weeks followed by oral fluconazole for 6 to 12 months. This regimen should be followed carefully due to the nephrotoxicity of amphoceterin B formulations. These treatment recommendations are all based off of recommendations from reports and case series.²⁵

The treatment for fluconazole-resistant infections caused by organisms such as C. glabrata is more limited than those caused by C. albicans.^47,51–53 Due to its resistance to fluconazole, the preferred treatment of C. albicans osteomyelitis are echinocandins followed by step-down therapy with oral voriconazole as long as the isolate is susceptible.^3,54,55 Due to the chance of cross-resistance between voriconazole and fluconazole, susceptibilities must be understood beforehand. The best experiences in treating hematogenously spreading C. glabrata infections is with amphotericin B.^51-53

In a review of 207 cases of Candida osteomyelitis reported between 1970 and 201, 44 percent of subjects were treated with antifungal therapy alone, 5 percent with surgery alone and 48 percent with both surgery and antifungal therapy.⁵⁶ Among the 92 patients treated with antifungal agents alone, 97 percent had a positive response, but 16 (17 percent) relapsed. There was no reported benefit of one antifungal treatment over another in this study. Notably there was a relapse rate of 43 percent among patients receiving both antifungal treatment and surgery. The authors postulated that many patients relapsed as a result of a therapy that was too short in duration. It is difficult to determine why the relapse rates were so high without further information about the type of antifungal used and the duration of treatment.

Empirical therapy

In certain contexts, empirical treatment of patients with vertebral osteomyelitis is warranted. Gram-negative stain and culture results in particular necessitate treatment with an empirical regimen of antimicrobials that are effective against the most common sources of vertebral osteomyelitis, including staphylococci, streptococci and gram-negative bacilli. Such treatment consists of vancomycin and cefotaxime, ceftazidime, ceftriaxone, cefepime or ciprofloxacin. Though rare, if patients present with positive anaerobic cultures, such coverage is warranted and would involve metronidazole added to the above treatments.⁵⁷ Duration of therapy varies from patient to patient, but in general it is recommended to treat for 6 weeks but may be extended for more resistant organisms.^57–59 Follow-up should be based on the response to therapy and the overall health of the patient.

Surgical intervention

Surgical debridement plays an important role in the treatment of many of these infections. The only absolute indication for surgery is a progressive neurological deficit or sepsis. Relative indications for surgery include:

• Failure of medical management (including six weeks of IV antibiotics with which the patient has been compliant)
• Progressive bony destruction
• Static neurological deficit that has not improved
• Fracture
• Instability
• Recalcitrant pain
• Spinal cord level (cervical or thoracic) compressive pathology

Prognosis

The most serious complication of vertebral osteomyelitis is neurologic impairment secondary to abscess formation or bony collapse. Back pain may fade with therapy, or it may persist. Minimizing the time between the onset of symptoms and the initiation of appropriate therapy is the best way to reduce morbidity and mortality. Mortalities due to vertebral osteomyelitis have decreased to less than 5 percent, and the rate of residual neurologic deficits among survivors is less than 7 percent.²²

In a retrospective study including of 260 patients with vertebral osteomyelitis that had long-term follow-up, 11% of patients died, while residual complications and disability occurred in 33%. Relapse occurred in 14% and S. aureus was associated with increased risk for relapse diagnosis.⁶⁰ S. aureus infection was associated with increased risk of relapse. Complications included neurological deficit (16%) and persistent back pain (32%).

A retrospective study of 253 patients with vertebral osteomyelitis investigated the long-term outcomes in such cases with a median duration of follow-up 6.5 years.⁶⁰ Relapse occurred in 14% of patients, and residual symptoms occurred in 31%; 11% died. Surgery was performed in 43% of patients and was successful in 79% of cases. Results of this study should be interpreted with caution, since cases were collected over a long time period, (median duration of follow-up was 6.5 years) which means that some cases occurred prior to the development of modern diagnostic modalities. A longer time to diagnosis, neurologic compromise and hospital acquisition were identified by the authors as major independent risk factors for the adverse outcomes of vertebral osteomyelitis.

Conclusion

Vertebral osteomyelitis occurs via hematogeneous spreading from a distant site of infection, direct inoculation from trauma or spinal surgery, and contiguous spread from adjacent soft tissue infections. Staphylococcus aureusis the most responsible organism for vertebral osteomyelitis. The major clinical manifestations of vertebral osteomyelitis are spinal pain, with or without fever. Pain to percussion over the infected area is a common physical finding. Elevated erythrocyte sedimentation rate and C-reactive protein are the two most common laboratory abnormalities. MRI is the most sensitive imaging modality with which vertebral osteomyelitis can be detected. Vertebral osteomyelitis can be confirmed by biopsy of the infected intervertebral disc space or vertebral bone. Blood cultures are positive in a majority of patients, and a biopsy may not be necessary for patients with clinical and radiographic findings typical of the infection along with positive blood cultures with a likely pathogen. Most cases of vertebral osteomyelitis respond to antimicrobial therapy, and surgery is necessary in a minority of patients with vertebral osteomyelitis. Prompt surgery is warranted for patients with a progressive neurologic deficit or septicemia. Surgery may be considered for other indications including epidural or paravertebral abscesses and/or cord compression. Antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed. The exceptions to this rule are neurologic compromise and sepsis where empirical antibiotic therapy is useful. Duration of antibiotic treatment for bacterial infection is typically 6 weeks at a minimum, and longer durations are warranted in a case-specific manner.

Epidural abscesses

Epidemiology

Epidural abscess is an uncommon but serious pyogenic infection with significant morbidity and mortality. Abscesses that are entrapped within the spinal column can impinge and compress the neurologic structures and cause immense issues and even death. Spinal epidural abscesses (SEA) are more common than intracranial epidural abscesses.⁶¹ Although SEA is an uncommon disease, evidence suggests that incidence may have increased over the last few decades.^62,63 From 1975 to 1998, for example, the incidence increased from 0.2-1.2 to 2.5-3.0 cases per 10,000 hospital admissions.⁶⁴ This increase may be due to an aging population or increased sensitivity of modern diagnostic modalities, particularly the increased sensitivity of magnetic resonance imaging (MRI).⁶⁵

A study reported the first published population-based incidence of spontaneous epidural abscess. During a ten year period, the occurrence in a county in Minnesota was 0.88 case/100,000 person-years (95% CI 0.27-1.48).⁶⁶ Additionally, another report found that radiographic evidence of an epidural abscess was reported in 64 of 167 patients (38%) with hematogenous vertebral osteomyelitis due to methicillin-susceptible S. aureus (MSSA) or gram-negative bacilli.⁴⁰ Epidural abscess was more common in patients with MSSA than it was in patients with gram-negative bacilli (47% versus 29%). SEAs are most prevalent between ages 50 and 70.⁶⁴

Risk factors

Multiple medical comorbidities have been shown to be risk factors for SEAs, including diabetes mellitus, tattoos, intravenous drug abuse, alcoholism, HIV infection, trauma, acupuncture, vertebral osteodiscitis, bacteremia, hemodialysis and paraspinal injections.^67,68 There is also a risk of SEA with epidural catheter placement. Epidural catheter placement has demonstrated an incidence of abscesses ranging from 0.5 to 3 percent.^4,69–71 A review of over 500,000 pregnant women undergoing epidural catheter placement in the United Kingdom had only a single SEA event occur, which suggests that SEA risk is potentially lowered when catheters are placed for shorter durations of time.⁷² In considering a diagnosis of SEA, these risk factors may often be absent, and this poses a challenge to reaching an early detection of SEAs.

Etiology

The main bacteria that causes SEAs is S. aureus, which accounts for about two-thirds of cases caused by pyogenic bacteria.^{42,62,73–75} Though the main cause of SEAs is S. aureus other causative organisms include gram-negative bacteria, streptococci and coagulase-negative staphylococci.^42,62,73 In various parts of the developing world, Mycobacterium tuberculosis is a more frequent cause of SEAs.⁷⁶ It will be discussed in the section on Granulomatous Infections of the Spine.

Skin and soft tissue infections as well as complications of spinal surgery, epidural catheters left in place for pain control and invasive procedures account for the most common origins of infection. SEA infections due to epidural catheters can be a result of contamination at the time the catheter is inserted, by bacteria ascending through the catheter from normal skin flora following insertion, from injection using contaminated syringes or local anesthetic solutions, or by hematogenous seeding from bacteremia while the catheter is in place.⁷⁷

Infection control is crucial when placing catheters and performing procedures that may place patients at risk for SEAs. The importance of infection control measures to prevent SEAs associated with catheter placement was illustrated by a report indicating the importance of facemasks and sterile technique while epidural catheters are being placed.

In this study, the infecting organism was isolated from nasal swabs taken from the physician who placed the catheter.⁷⁸

Pathogenesis

Bacteria can gain access to the epidural space via the blood or by direct inoculation into the spinal canal or by direct extension such as from vertebral osteomyelitis or a psoas abscess or a septic facet joint. Focal pyogenic lesions often precede SEAs, and these involve the vertebral disc or the junction between the disc and the vertebral body (pyogenic infectious discitis).^26,79 As the pyogenic inflammation progresses and the abscess extends into the epidural space, damage can be caused to the spinal cord. Although the full length of the spinal column may be affected, longitudinal extension is most common between three to five spinal segments when infections are in epidural spaces.⁷⁴ SEAs sometimes do occur at noncontiguous lesions.

Despite the higher chance that epidural abscesses occur at contiguous sites of the vertebrae, they can sometimes occur at noncontiguous locations in the spine. Skip lesions were shown to occur in a retrospective study in 9% of adult patients with SEAs.⁸⁰ Such noncontiguous lesions were more common in patients with a delay in presentation (a week or longer), a simultaneous area of infection outside of the spine or paraspinal region, and an ESR of greater or equal to 95 mm/hour at presentation. The authors suggested the use of these three parameters as indications for skip lesion presence, but more data must be obtained to verify this finding. At the time of surgical drainage, it is common to find granulation tissue within the abscess if the abscess has been present for more than two weeks. In acute cases, epidural abscesses may contain frank pus.

Clinical presentation

The clinical presentation of SEAs is variable but classically involves fever, spinal pain and neurologic insufficiencies. However, only a small portion of patients present with all three of these symptoms at presentation.^27,81,82 Commonly patients will initially present with severe back pain alone. This may eventually be followed by radicular symptoms, weakness, bowel/bladder dysfunction, or even paralysis.⁷⁴

Spinal Epidural Abscess is very difficult to diagnose using routine lab work due to a lack of specificity in markers as well as a diverse array of lab values in patients with SEAs. The hematocrit is often normal and the leukocyte may be high or normal. Additionally, the ESR is often high in both SEA and vertebral osteomyelitis. In an emergency department patient population, only 60% of patients that were diagnosed with SEA had leukocytosis at their initial visit.²⁷ In contrast, other studies have shown the ESR to be elevated (>20 mm/hour) in 100% of patients with SEA.^27,83 C-reactive protein (CRP) has also been shown to be elevated in as high as 87% of patients with SEA. However, while the sensitivity of CRP and ESR is high, it is important to keep in mind that as many as 33% to 50% of patients with spinal pain not related to SEA can have elevated markers suggesting less specificity for these diagnostic tests.

Diagnostic approach and imaging

SEA is a rare cause of back pain, and thus is a diagnosis of exclusion. Once the diagnosis of SEA is considered, it is important to image the spinal column using MRI. MRI is the preferred test due to its ability to detect infection early in its course as well as provide higher level of visualization of the extent of the infection^75,84 (Fig. 1-1 to 1-4). Isolating the causative organism is a proper subsequent step to detection, and CT-guided needle biopsy directly obtained from the epidural abscess is beneficial.⁸⁵

Determining epidural soft tissue edema versus epidural abscess is critical. MRI can make this distinction. Classic characteristics of SEA using MRI as the preferred imaging modality have been well described and are quite distinctive.^40,86–91 Abscesses tend to have low or intermediate intensities on T₁-weighted MR sequences and high or intermediate intensity on T₂-weighted images. Hyperintensity is usually visualized within the fluid portion of the abscess on T₂-weighted images and hypointensity on T₁-weighted images.⁹² A series of case reports has shown that Gadolinium-enhanced MRI imaging is useful in determining the age and consistency of an SEA (pus or granulation tissue)⁹². Liquid pus reveals itself as an area of low signal intensity on T₁-weighted images, whereas a rim of tissue that enhances after the injection of Gd is representative of granulated tissue.^40,86,92 Comparatively, epidural soft tissue edema usually manifests as diffuse hypointensity of T1-weighted images, hyperintensity on T2-weighted images, and contrast enhancement. Some studies have suggested that the presence of ring-like or linear dural enhancement is an indication for surgery.^28,93 The authors believe that CT with contrast is not nearly as sensitive as MRI in making the diagnosis or determining the extent of infection or the degree of stenosis. Myelography is contraindicated in the setting of an active epidural infection.

Differential diagnosis

S. aureus is not unique to SEAs. It is the major pathogen in vertebral osteomyelitis and discitis as well,⁶⁷ so the combination of back pain and infection by the major pathogen are not specific to SEA. SEAs share symptoms with a variety of conditions, and this warrants the consideration of the following diseases as differential diagnoses: metastatic tumors, disc and degenerative bone disease, vertebral discitis and osteomyelitis, meningitis and herpes zoster before to the appearance of skin lesions.⁶¹

Treatment

Treatment for spinal epidural abscesses involves reducing the size, eliminating the mass, and eliminating the pathogenic organism. A combination of aspiration, drainage and antibiotic regimens are useful in achieving these goals. Medical management may be considered in neurologically stable patients with an epidural abscess in the lumbar spine that are in a monitored setting and are receiving IV antibiotics. If extremity weakness is present, surgical intervention should be considered in the absence of any contraindications.^75,94 In the setting of significant weakness or paralysis surgery should be performed as early as possible.⁶⁷ The earlier one performs surgical decompressions and drainage the better. If the MRI findings indicate spinal cord compression or severe stenosis, even in the absence of signs or symptoms or neurologic compromise, surgery

should be considered. Patients with a neurological deficit should be placed into an ICU setting with a maintained mean arterial pressure >80, and carefully monitored. Intravenous steroids should be avoided.

Though targeted therapy to a causative organism is preferred, empirical therapies targeting likely pathogens are more often employed due to a lack of controlled evidence around the best antimicrobial treatments of SEAs. Appropriate empirical IV regimens include vancomycin for empirical MRSA coverage plus either cefotaxime or ceftriaxone or cefepime or ceftazidime. Pseudomonas aeruginosa is associated with intravenous drug abuse,⁶⁴ and when this pathogen is suspected one should use cefepime or ceftazidime. Subsequently, once a known pathogen is identified via culture, the treatment regimen should be simplified to antibiotics directed against those specific pathogens.

If the organism is determined to be S. Aureus, vancomycin should be used.^95,96 However, a drawback to vancomycin is that it poorly penetrates cerebrospinal fluid (CSF).^96,97 If MSSA is discovered, treatment should be changed to nafcillin or oxacillin. Vancomycin should be continued if the organism is methicillin resistant. In the case of poor vancomycin CSF penetration, drug penetration and efficacy can be augmented by adding rifampin to vancomycin because it achieves bactericidal concentrations in the CSF.^95,96,98

Duration of therapy for a patient with SEA should occur on a patient-by-patient basis. The duration of antimicrobial therapy generally provides cure in 4-6 weeks of treatment.^61,99 Follow up MRIs should be performed as needed. For patients who also have osteomyelitis associated with an SEA, therapy should continue for approximately six to eight weeks.⁶²

The primary forms of surgical intervention are decompression of neural tissue and stabilization of bony elements of the spine. Another option is decompression alone.^{74,88,100,101} The main factor in deciding the surgical approach is the location of the abscess. At the time of surgery, a biopsy should be taken to identify a causative organism. As with the trend of infections of the spine, surgery should be performed as quickly as possible in the setting of a neurologic deficit. Those treated non-surgically continue to exhibit high failure rates (41-42.5%) accompanied by increased morbidity (up to 22% permanent paralysis) and mortality (rates from 1.8% to 25%).^102–108 Comorbidities worsen the overall prognosis in patients with SEAs. They predispose these patients to a higher incidence of perioperative complications after surgery, particularly if they have a neurological deficit.

Prognosis

Outcomes are often measured by examining mortality and recovery rates from neurological deficits.⁶⁴ The prognosis for patients with SEAs is generally poor. Comorbidities enhance the risk of death, and patients generally die from sepsis or other complications. About 5% of patients with SEA die due to sepsis or other complications.^64,67 In a retrospective study, permanent paraplegia has been observed to occur in 4%-22% of patients. Neurologic recovery is unlikely if paralysis is present for greater than 24 hours before surgery.^{19,42,67,74,103,109} However, it is unclear without prospective, randomized data (which would be impossible to perform due to ethical concerns) whether earlier surgery would have reduced the incidence of permanent paraplegia or whether patients who go to surgery late are simply more likely to have a poor prognosis due to other confounding medical factors. In some patients, the level of neurologic recovery post-op is related to the duration of the neurological deficit. However, the neurological recovery is also related to the severity of the initial deficit and there are many patients who have early surgery who still have a persistent postoperative deficit. In a population of emergency department patients previously mentioned, 37% of patients with an SEA had residual motor weakness after surgical debridement²⁷. Delayed diagnosis was associated with increased risk of residual weakness compared to patients with no delay in diagnosis (45% versus 13%). However, even in patients who had an early diagnosis, there was still a high rate of permanent neurological deficit.

Conclusion

Epidural abscess is a rare infection that can cause a neurologic deficit due to compression of the spinal cord. Quick diagnosis and proper treatment are critical to avoid complications and to improve the chances for eradication of the infection. Bacteria can enter the epidural space in a variety of ways. They can spread hematogenously, by direct extension from infected contiguous tissue, or via direct inoculation into the spinal canal by various procedures. Factors that increase the risk of developing SEAs are epidural catheters, diabetes mellitus, alcoholism, HIV infection, bacteremia and IV drug use. The most common causative pathogen of SEAs is staphylococcus aureus, as it is responsible for two-thirds of cases caused by pyogenic bacteria. Approximately one-third of patients have no identifiable source of their infection. In the two-thirds of patients where a path of entry was identifiable, the most common sites of origin are infections of skin and soft tissues and complications of spinal surgery or other invasive procedures, including epidural catheters that are left in place for pain control. SEA can initially manifest itself through a fever and general malaise. The classic diagnostic triad of SEA is fever, back pain and neurologic deficits although presentations vary significantly. Obtaining an MRI early is critical to evaluating the extent of the infection and planning treatment. Prompt surgical decompression of epidural abscesses that meet surgical criteria is critical to avoid a worsening neurologic deficit, maximize outcomes and successfully treat the infection.

Granulomatosis infections

Granulomatosis infections may be caused by fungi, bacteria and spirochetes. Due to their uncommon nature and similar clinical and histological features to each other, they have been grouped together.

The most common granulomatous infection of the spine is tuberculosis. Tuberculosis spondylitis (Pott’s Disease) will be described in detail while fungal and other granulomatous infections will be reviewed by outlining differences between them and tuberculous infections. Bacteria in the order of Actinomycetales cause chronic infections. This order includes Mycobacteriaceae, Actinomycetaceae and Nocardiaceae.

Tuberculosis

Epidemiology

Tuberculosis (TB) is a disease that dates to ancient times. Signs of skeletal TB have been reported from as early as 8000 BC in Europe from Neolithic remains.¹¹⁰ Skeletal tuberculosis accounts for approximately 10-35% of cases of extrapulmonary TB.^111-115 The most common form of skeletal TB is tuberculosis spondylitis (Potts Disease), which comprises about half of musculoskeletal TB cases.¹¹⁶ The incidence of tuberculous spondylitis varies considerably throughout the world and is usually proportional to the quality of public health services available. This illness is more common in underdeveloped countries where malnutrition and overcrowding are major problems. In affluent countries, the incidence has decreased in the last 30 years, and it is now uncommon.¹¹⁷ A neurologic deficit will develop in 10-47% of patients with Potts disease.^118-129 In developing countries, the disease is still a significant source of morbidity and mortality. In Asia and Africa, a large percentage of patients are children.^{1,21,128–134}

Etiology

Spinal tuberculosis may occur from hematogenous dissemination from a primary focus. The pulmonary and genitourinary systems are the most frequent routes of infection, but the disease may also arise from other skeletal lesions.^125,135,136 The infection reaches the skeletal system through vascular channels, generally the arteries, as a result of bacteremia, or in the axial skeleton through Batson’s plexus of veins.^137,138

Pathogenesis

The route of spread of early spinal TB is similar to that of other pyogenic infections of the spine. During primary M. tuberculosis infection, bacteremia may lead to seeding of organisms in bone and/or synovial tissue which may subsequently spread upon failure of host immune defenses.¹³⁹ After the primary infection, a foci of infection may be contained by the cellular immune response. Mycobacterium tuberculosisis the most common pathogen.

Active tuberculosis (TB) disease can develop quickly or very slowly. In highly pervasive areas, musculoskeletal TB often presents in young patients during the year following primary lung infection. Later reactivation of infection is more common outside endemic areas, and this occurs mostly in adults. The three main types of spinal involvement are peridiscal, central, and anterior.¹⁴⁰ Posterior tuberculosis involvement is uncommon.

Clinical presentation

In the classic presentation of tuberculosis spondylitis, the patient complains of local back pain and tenderness, gibbus and a cold absess and a prominent spinal deformity.¹⁴⁰ In industrialized countries, presentation is generally early but in underdeveloped countries the disease can be far more advanced and involve more severe symptoms such as paraplegia, kyphosis and draining sinuses.^{1,126,136,141} Neurologic complications are common in the thoracic and cervical regions and are present at a rate of 23 to 76%.¹⁴²

The lower thoracic and upper lumbar regions are most commonly affected by Pott’s disease.^132,140,143 Adjacent vertebrae may be affected. Once two adjacent vertebrae are involved, the infection spans the adjoining intervertebral disc space. Compared to bacterial vertebral osteomyelitis, this process usually occurs later in Pott’s disease and may have the appearance of relative disc sparing. However, the bony endplates and vascular channels are affected, and thus the disc tissue eventually undergoes necrosis. In some infections, this may lead to intervertebral disk space narrowing and ultimate collapse of that space. This collapse may result in spinal kyphosis and ultimate neurologic compromise.¹⁴⁴ Soft tissue masses are common at the site of infection, and delayed diagnosis of Pott’s disease is a problem in endemic areas.^138,145

Diagnostic evaluation and imaging

There are a number of radiographic findings that can help a physician detect TB spondylitis in their patient. Radiographic abnormalities are usually first observed in the anterior aspect of a vertebral body and are characterized by demineralization of the end plate and a loss of definition of the bony margins.¹⁴⁶ Similar to pyogenic infections, peridiscal involvement and subsequent bone destruction may be evident. The initial radiographs often show far advanced bony changes, in contrast to pyogenic infections in which radiographs may be normal on first presentation. Central body involvement can look like a tumor and cause greater and earlier bone collapse than peridiscal involvement.¹⁴⁰ Occasionally, lumbar spine radiographs will demonstrate calcification in the psoas muscle in cases with a long standing abscess.¹²⁰ Additional presentations include the presence of a paravertebral abscess and pulmonary involvement as observed by a chest radiograph. In some patients, spinal TB presents with osteolytic lesions occurring at multiple sites in the absence of disc space involvement. Spinal TB without disc involvement can be observed in approximately 50% of cases.¹⁴⁷

Spinal tuberculosis is a challenging disease to diagnose, as it resembles other disease entities. The greatest challenge is considering the diagnosis since there is no evidence of active disease in more than half of cases. A person’s country of origin obtained through the history may help with the diagnosis. The ESR generally is increased but is nonspecific. A tuberculin purified protein derivative test (PPD) is usually positive and indicates present or past exposure to Mycobacterium.¹³² Though such tests may be useful in reaching a confirmatory diagnosis, a recent, retrospective study of 145 treated spinal TB cases reported that 85% of cases with tuberculosis of the spine can be diagnosed through MRI alone.

Tuberculosis of the spine is difficult to distinguish from pyogenic infections of the spine as rim enhancement has been reported to suggest both tuberculosis and pyogenic spondylitis.¹⁴⁸ Two reported useful findings on MRI that are characteristic of Pott’s is thin and smooth enhancement of the abscess wall and well-defined paraspinal abnormal signals.¹⁴⁸ These findings are in contrast with the thick and irregular enhancement of abscess wall and paraspinal abnormal signal that are suggestive of pyogenic spondylitis. Additionally, tuberculous spondylitis has been reported to show a subligamentous spread to three or four vertebral levels and multiple vertebral or entire body involvement.

Therefore, contrast MRI is essential for distinguishing between these two common infectious sources.

Differential diagnosis

The differential diagnosis of Pott’s disease includes degenerative disc and facet joint disease, vertebral body collapse due to osteopenia, spondyloarthropathy, pyogenic spinal infection and malignancy. These each can present with similar clinical findings. Most of these conditions can be distinguished with imaging studies.¹³⁹

Treatment

Antituberculous treatment for patients with spinal TB should be started as early as possible. Eradicating the infection and preventing a neurological deficit and spinal deformity are the primary goals of management for patients with spinal TB. The drug regimen depends on whether or not the patient has drug-resistant TB or is HIV positive.

The optimal duration of therapy for treatment of spinal TB is not known. For most patients receiving first-line agents (isoniazid, rifampin, pyrazinamide and ethambutol), six to nine months of therapy is satisfactory.¹⁴⁹ A longer duration of therapy (9-12 months) is necessary for patients whose regimens do not include rifampin and/or who have extensive disease.^149,150

Surgery

Surgical intervention is necessary for patients with spinal disease and severe static neurological deficits (e.g., paraplegia) on presentation and destabilization of the spine.¹⁴⁹

Decompression, use of hardware for stabilization of spine, abscess drainage, and debridement of infected tissue are common surgical procedures that are performed.^132,151 Due to advances in technology, minimally invasive surgical approaches are now possible through video-assisted thoracoscopic anterior surgeries, and these procedures have been used successfully to manage patients with neurological symptoms who may or may not also have prevalent bony destruction involving the thoracic or lumbar spine.¹⁵²

In general, abscess drainage is universally indicated only if the patient is septic from the abscess or the abscess is extensive and/or results in a neurologic deficit. Paravertebral abscesses in the thoracic spine can be drained effectively by a costotransversectomy.¹⁵³ Large psoas abscesses may be drained by a retroperitoneal approach.¹³¹ Tuberculous abscesses are not generally liquid in nature and are characterized as phlegmonatous.

Spinal TB is predominately an anterior spinal disease. Cord compression by granulation tissue, casseous material and abscess largely occurs in the front of the spine. The anterior surgical approach was popularized by Hodgson et al.¹⁵⁴ and Benli et al.¹⁵⁵ in a series of 100 patients. They reported 19.8°±7.3° correction of kyphosis with a preoperative local kyphosis angle of 22.5°±11.0° (range, 10°–80°) improving to a postoperative angle of 2.7°±3.9° (range, 0°–22°). The latter study reported no apparent pseudarthroses, and all

patients healed without recurrence and reactivation.¹⁵⁵ An anterior approach with grafting and instrumentation can be done as a stand-alone procedure in some cases minimizing blood loss, operative time and graft dislodgement. Posterior instrumented fusion can be done after anterior decompression either as a two-stage or single stage procedure.^156,157 In contrast, other authors have described effective treatment of spinal TB using all posterior approaches with transpedicular, lateral extracavitary or costotransversectomy approaches to gain access to the anterior column of the spine.¹⁵⁷ These techniques avoid possible complications of violating the thoracic or abdominal cavities.¹⁵⁸ However, these approaches require technical expertise to avoid untoward neurologic or vascular complications.¹⁵⁹

While the ideal surgical approach depends on surgeon experience and disease extent, a recent comparative study of surgical management by a posterior only and combined posterior and anterior approaches for thoracic spinal TB in the elderly concluded that the posterior only procedure had better clinical outcomes.^157,160 Another study comparing anterior and posterior approaches in the treatment of thoracic and thoracolumbar TB found that both approaches are comparable with regards to duration of surgery, blood loss, fusion and functional outcomes. However, the posterior approach was associated with significantly better kyphosis correction.^157,161

Continuous destruction of the anterior column and progressive anterior collapse of the spine by TB despite anti-tubercular treatment may result in kyphosis. After healing of the spinal infection, the post-TB kyphosis in adults may be static, but kyphosis progresses dramatically in 40% of pediatric cases.^157,162 Since the advent of posterior-only vertebral column resection (PVCR) by Suk et al.,¹⁶³ great results have been reported from investigators using PVCR for tubercular deformities of the spine,^{158,163–169} A study of 17 patients reported an average kyphosis correction rate of 68.7° ±6.5°.¹⁶⁴ While PVCR is a powerful deformity correction technique, complication rates as high as 40% have been described in the literature.¹⁷⁰ This procedure is recommended only for severe kyphosis either in active or healed disease.

New techniques in minimally invasive spine surgery are emerging for the treatment of various degenerative spinal disorders. Video-assisted thorascopic surgery (VATS) was developed to decrease the approach related morbidity associated with thoracotomy. VATS is a great alternative to conventional thoracotomy with minimal morbidity. Previous work has examined the role of VATS in spinal TB. Good clinical, neurological and fusion outcomes have been reported in VATS treated tubercular spondylitis.¹⁷¹ VATS-assisted surgical decompression is a safe and effective means for anterior debridement and fusion in tuberculosis of the spine in select patients.^155,172 The efficacy of minimally invasive spinal decompression through an interlaminar approach combined with local chemotherapy in patients with thoracic or lumbar TB and spinal epidural abscess has also been examined.¹⁷³ A minimally invasive spinal canal decompression, focal debridement, and catheter drainage through a posterior interlaminar approach has been described. Satisfactory patient outcomes with this minimally invasive approach, in combination with local and systemic chemotherapy, have been shown.

Prognosis

With tuberculous spondylitis, the prognosis is generally good, yet it depends on the age and general health of the patient, the severity and duration of the neurologic deficit, and the treatment selected. A study used logistic regression analysis to evaluate outcomes of 43 patients with Potts paraplegia at six months. This group found that the most important prognostic factor that predicted six-month outcome included initial muscle power, paraplegia score, sensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs).¹⁷⁴ Patients with lower paraplegia scores and mild weakness were more likely to recover completely by six months than more severe cases. Another study of 129 subjects was conducted in an endemic region that showed recovery in 70% of patients within 6 months of treatment.¹⁷⁵

Conclusion

Tuberculosis spondylitis (Pott’s disease) is the most common form of skeletal TB, and it usually affects the lower thoracic and upper lumber region. Once two adjacent vertebrae are involved, infection can involve the adjoining intervertebral disc space, yielding vertebral collapse. Consequential kyphosis can lead to cord compression and paraplegia. The most common symptom of Pott’s is local pain that increases in severity over weeks to months. Muscle spasm and rigidity are also common. Constitutional symptoms such as fever and weight loss are relatively uncommon. Diagnosis of spinal TB is established by culture of infected tissue, which is obtained through open or aspirate biopsy.

Radiographic imaging, particularly MRI, is useful in identifying Potts disease as it allows for imaging of bony and muscular tissue. Treatment of Potts disease consists of antituberculous therapy similar to the regimens for pulmonary tuberculosis. Optimal duration of therapy is uncertain. For patients receiving first-line agents in the absence of extensive disease, 6 months of therapy is suggested. A longer duration of therapy, 9-12 months, is warranted for patients on regimens that do not include rifampin and/or for patients with extensive or advanced disease. Surgical intervention is warranted in the presence of neurological deficits and/or worsening deficits while on appropriate therapy, as well as for patients with spinal disease and deformity at presentation.

Actinomycosis

Actinomycosis israelii is a slowly growing, facultative or anaerobic, filamentous, gram-positive bacteria. The disease expresses itself in a manner similar to that of true fungi. Actinomyces species are found in the flora of the oral cavity and vagina and may cause infection with abscess formation and draining sinuses. The disease is noted for causing chronic suppurative infections with external sinuses that discharge distinctive aggregates of organisms (“sulfur granules”).^176,177 Surgery, infection or trauma are required by the organism for penetration into the mucosa.

Hard, fibrotic walls typically characterize lesions, with granulation tissue surrounding regions of pus. Sinus tracts extending to the skin or into other organs are often seen in more chronic infections.¹⁷⁶ The most classic presentation of the disease is the cervico-facial form, accounting for approximately half the cases, followed by thoracic, abdomino-pelvic and cerebral invasions.¹⁷⁸ In much rarer cases, A. meyeri has been identified in the spine. It is usually secondary to infection of contiguous tissues rather than to hematogenous spread.^178–180

The diagnosis of actinomycosis is challenging as it can mimic other diseases such as malignancies, and the procedures required for accurate microbiological identification of the pathogen are challenging. The main differential diagnoses include all chronic and suppurative infectious processes such as nocardiosis, tuberculosis, spondyloarthritis and primary or secondary malignancies.¹⁷⁸ Actinomycosis usually spares intervertebral discs and involves adjacent pedicles and transverse processes, as well as neighboring ribs.^178,179 Microbiological diagnosis requires culturing clinical specimens such as pus, enriched in culture media and in appropriate culture conditions. Actinomyces species appear as “molar-tooth” colonies on agar.¹⁷⁸ Species identification is achieved through complex phenotypic testing and mass spectrometry or 16S rRNA sequencing. Penicillin G is the best treatment of actinomycosis; however, Actinomycosis species are susceptible to various antimicrobials including tetracyclines, erythromycin, clindamycin, cephalosporins, carbapenems, streptomycin and chloramphenicol.¹⁷⁸ A long duration of treatment is suitable to prevent relapses, and a combined medico-surgical approach is required for complicated disease forms.¹⁷⁸

Brucellosis

Brucellosis is caused by an aerobic, gram-negative coccobacillus commonly found in domestic animals. Brucellosis is transmitted to humans by direct contact, by ingestion of contaminated products and by inhalation of aerosols.^181–184 Brucellosis is one of the most widespread zoonoses worldwide.¹⁸⁵ Brucellosis is a systemic infection with a broad clinical spectrum, ranging from asymptomatic disease to severe and/or fatal illness.¹⁸⁶ The main presentations are acute febrile illness, with or without signs of localization, and chronic infection. Focal infection occurs in about 30 percent of cases, and brucellosis can affect any organ system.^186–189 Osteoarticular involvement is the most common presentation. The sacroiliac joints and large joints of the lower limbs are most frequently involved.^190–193 Spondylitis is a serious complication of brucellosis, and it is more prevalent in older patients and patients with prolonged illness prior to treatment. Spondylitis occurs more frequently in lumbar vertebrae.^12,194,195 Paravertebral, epidural and psoas abscess can occur in the context of brucellar spondylitis.^12,195

The characteristic radiologic features of brucellar spondylitis include predilection for the lower lumbar spine, intact vertebral architecture despite evidence of diffuse vertebral osteomyelitis, disc space involvement, minimal associated paraspinal soft tissue involvement, and absence of gibbous deformity.^184,196 MRI findings are similar to TB, except that TB often produces more severe changes with more deformity and abscess formation.¹⁹⁶

Treatment for Brucella spondylitis should consist of two antibiotic agents for at least 12 weeks. Patients respond better to doxycycline plus streptomycin than to doxycycline-rifampin.^194,197 The duration of therapy is at least as important as the choice of

antimicrobial agents. In one meta-analysis, the failure rate for patients treated less than 6 weeks was 43%; the failure rate for patients treated more than 12 weeks was 17%.¹⁹⁸ Surgery may be warranted in the context of spinal instability, persistence or progression of neurological deficit, vertebral collapse or localized abscess (epidural or paravertebral).^186,199

Fungal infections

The fungi that cause disease in humans can be classified as either opportunistic or pathogenic fungi. The opportunistic fungi (Aspergillus, Candida, Mucorspecies) rarely cause disease in healthy people, but do cause infection in immunocompromised hosts. Pathogenic fungi (Blastomyces dermatitis, Coccidioides immitis, Histoplasma capsulatum) can produce spinal infections (5-10%) in healthy persons.^200,201Fungi such as Coccidioides immitis and Blastomyces dermatitidis are limited to specific geographical areas whereas Candidaand Aspergillus are two organisms that most commonly cause fungal infections of the spine worldwide.^202–204 Candida and asperigillus are normal commensals of the body and produce disease in susceptible organisms when they gain access to the vascular system through intravenous lines, during implantation of prosthetic devices or during surgery.²⁰¹ For the other fungi, spinal involvement usually is the result of hematogenous or direct spread of organisms from an initial pulmonary source of infection.²⁰¹ Vertebral body involvement can lead to vertebral compression fractures and gross deformities of the spine. Infection can spread along the anterior longitudinal ligament and can lead to psoas or paravertebral abscesses. Fungal infections may produce inflammatory reactions ranging from chronic inflammation to suppuration with granuloma formation.^201,205

Early recognition of such conditions requires a high index of suspicion, a proper travel history and a detailed physical examination. Treatment for these fungi involves the use of prompt and appropriate antifungals and constant monitoring of clinical progress. Surgery is necessitated when resistance to therapy, spinal instability and neurologic deficits are indicated. Anterior debridement and stabilization with spinal fusion are preferred in such contexts.^206,207 Prognosis varies, and it depends on the premorbid state of the patient, the type of organism and the timing of treatment. The unique characteristics of the fungi causing vertebral osteomyelitis are discussed in the sections below.

Coccidioidomycosis

Coccidioidomycosis is caused by the dimorphic fungi, Coccidioides immitis or Coccidioides posadasii. These organisms are endemic to certain arid regions of the western hemisphere. Inhalation is the most common route of infection, and primary infection usually goes unrecognized.^208,209 Infection can disseminate beyond the lungs and the risk of this dissemination is estimated to be approximately 4.7 percent of recognized infections.²¹⁰ When disseminated infection occurs, it usually is evident within weeks after initial exposure. Extrapulmonary dissemination is normally a result of hematogenous spread of the organism. Vertebrae are a common site for coccidioidal osteomyelitis with lesions present as single or multiples with occasional involvement of the sacrum and ileum.

The management of these lesions is especially important because of their potential impact on the spinal cord and mobility. Some may require surgical debridement and stabilization in order to control the infection. Identifying which lesions will benefit from surgery is challenging, and practices among different physicians vary significantly in management of these lesions. There are a couple of useful ways to image such infections. Radionuclide bone scans are useful to identify possible sites of infection.²¹¹ MRI with gadolinium enhancement has also been noted to be useful in identifying the extent of individual lesions.²³

Upon completion of these studies and neurologic evaluation, patients should be managed depending on whether or not there is risk of or immediate cord compression and instability of the spinal column. For patients with cord compression, surgical decompression is warranted. For patients without cord compression and spinal instability, antifungal therapy may be initiated without immediate surgical intervention. Subsequent management depends upon the evolution of lesions as evidenced by neurologic exam and repeated MRI (within one or two months). If lesions are progressive, surgery can be reconsidered.

The drug of choice for treating such infections is a oral azole antifungal agent. Amphotericin B is usually implemented in patients with lesions that are worsening rapidly or are located in the spine. Surgical debridement or stabilization is critical as an adjunctive treatment in certain cases. Of note, for those patients who positively respond to antifungals, there is a high chance for relapse once treatment stops. The management of coccidioidomycosis in immunocompromised hosts who may require indefinite therapy presents additional challenges.

Blastomycosis

Blastomycosis is a systemic pyogranulomatous infection that primarily involves the lungs and arises after inhalation of the spore of Blastomyces dermatitidis. Hematogenous spread frequently occurs and can involve almost any organ. North America has reported the majority of cases of blastomycosis. Areas that can be considered at risk include the southeastern and south-central states bordering the Mississippi and Ohio River basins.²¹² Blastomycosis has been additionally reported in Africa, South America and Asia.

Extrapulmonary disease is usually seen in conjunction with active pulmonary infection. Among other sites, CNS and vertebral involvement are possible in patients infected with Blastomycosis. Though uncommon, CNS infection is possible and may present as meningitis, epidural abscess or intracranial abscesses.²¹³ Osteomyelitis is among the most common extrapulmonary manifestations of blastomycosis after cutaneous involvement, and it occurs in up to 25 percent of patients with multiorgan disease.²¹⁴ Any bone may be involved, but the most common are the vertebrae, pelvis and sacrum. Patients often present with soft tissue swelling or chronic draining sinus tract adjacent to the lesion of osteomyelitis, and there is usually little bone pain associated.²¹²

Like many other infections, vertebral disease can be similar radiographically to tuberculosis, with anterior involvement of the vertebral body and destruction of the disc space.³⁰ Additionally, paravertebral abscesses occur with vertebral blastomycosis.²¹⁵ Diagnosis requires growth of the organism from a clinical specimen.²¹²

Treatment of disseminated blastomycosis is determined by the presence or absence of central nervous system infection. Amphoceterin B followed by oral itraconazole for 12 months has been shown to be effective in treating moderately severe to severe disseminated disease.²¹² Bone disease is harder to treat and more likely to relapse than other forms of blastomycosis.^212,216 Immunocompromised patients with blastomycosis should be treated with a lipid form of amphotericin B or amphotericin B deoxycholate intravenously for one to two weeks until improvement is observed.²¹² For patients with relapse in which immunosuppression cannot be reversed, itraconazole is recommended as a long term therapy.²¹²

Candidiasis

Candidiasis is typically a fungal infection of the skin or mucous membrane. Candidemia is rare in immunocompetent hosts. Causative organisms of infection include C. albicans, C. tropicalis, and C. glabrata. C. albicans. Typically, infection due to candida species occurs in the thoracic and lumbar spine. Very rarely cases have been reported in the cervical spine. Risk factors include central venous catheters, immunosuppressive chemotherapy and use of broad spectrum antibiotics.

Presentation of candida vertebral osteomyelitis includes back pain, fever and neurological deficits; however, fever and neurological deficits are not as common. Symptoms are present for greater than one month in 83% of patients.⁴⁷ Laboratory values such as white blood cell count are often normal however ESR is commonly elevated.⁴⁷ Diagnostic tests include MRI, CT guided biopsy and culture. If suspected, early MRI will aid in detecting pathologic lesions with the diagnosis being confirmed with cultures from a CT guided biopsy.

The treatment for candida spinal infections varies. If the infection is caught early enough, antifungal treatment can be sufficient to treat and cure the patient. Amphotericin B and azoles are widely used. In more progressive cases, disease can lead to vertebral destruction and compression of neural elements. In these cases debridement, fusion and stabilization combined with antifungal agents can eradicate infection.²¹⁷

Aspergillosis

Invasive aspergillosis can cause aspergillus osteomyelitis in sites such as the vertebrae, ribs and cranium among in patients. The most common species are A. fumigatus and A. flavus. Affected patients experience back pain and neurologic deficits. Risk factors that predispose patients to contracting this infection include corticosteroid therapy, widespread use of antibiotics and chemotherapeutic drugs.²¹⁸ Along with this, primary immunodeficiency, solid organ transplant, IV drug use, COPD and diabetes mellitus have also been shown to increase risk.³²

Aspergillus osteomyelitis is typically diagnosed by open biopsy and percutaneous biopsy. From this, organisms are obtained and revealed through direct culture or histology. MRI aids in looking for osteolysis, bone destruction and bone erosion.³² The most common feature of MRI include decreased signal intensity on T1-weighted images, increased signal on T2-weighted images and increased gadolinium contrast enhancement of T1-weighted images.³² Along with this, laboratory values of ESR and CRP are usually elevated.

Treatment consists of antifungal therapy and possibly surgical debridement. Acceptable antifungal agents include amphotericin B, itraconazole and voriconazole. As with candidiasis, spinal column instability or neural element compression is an indication for surgical intervention.

SECTION II: POSTOPERATIVE SPINAL INFECTIONS

Introduction

Postoperative spinal infections are a dreaded complication for both patient and physician. Despite advances in prophylactic antibiotics, surgical technique, sterilization technique, and pre and postoperative care surgical site infections continue to occur. As spinal surgery continues to become more sophisticated the number of invasive procedures, whether diagnostic or therapeutic, will certainly increase. Infection rates vary depending on duration and invasiveness of surgery, which calls for a deeper comprehension of the root causes for surgical site infections. It is imperative that surgeons understand the pathogenesis, risk factors, treatment and prevention as surgical site infection can have a negative effect on the overall outcome and satisfaction of the patient.

Epidemiology

The incidence of surgical site infections varies depending on certain variables such as invasiveness of surgery, operative time and use of instrumentation. Overall, spinal surgery has a higher rate of infection compared to orthopedic procedures such as hip and knee arthroplasties.²¹⁹ Incidence rates for spinal infection following surgery of .7% to 16% have been reported.^220–226

A study performed by Veeravagu et. al of 24, 774 patients who underwent spinal decompression and fusion showed 3.04% of patients had a postoperative infection; 1.16% were superficial and 1.89% were deep infections.²²¹ Other studies show an incidence rate of .6% to 5% after discectomy. Fusion without instrumentation has shown incidence rates of .4% to 4.3%. When looking at the use of internal fixation, this increases the rate of infection to 6.6 to 8.7%.^227,228

Infection rates are directly correlated with more complex surgeries; however, the exact reason is not clearly defined in the literature. It has been postulated that the increased amounts of soft tissue dissection allow for more bacterial colonization.²²⁹ Instrumentation also increases the risk of infection in patients. Micromotion of the instrumentation leads to granuloma formation and provides yet another medium for bacterial colonization.²³⁰ Operative time also plays a role in the incidence of surgical site infections. It has been shown that there is increased risk with procedures lasting longer than 3 hours, although this risk may be related to anesthesia risk.²³¹ Meticulous preoperative planning and sound execution can help lower incidence rates among patients following spinal procedures.

Pathogenesis

Bacteria must be present at the surgical site in large quantities (greater than 10⁵ organisms) in order for a clinical infection to occur.²²⁹ Bacteria may be introduced through direct inoculation from the patient’s skin, hematogenous spread from a distant source in the patient’s body, or soiling of the incision in the fresh postoperative phase.²³² Most infections however are a result of direct inoculation at the time of surgery.

Gram positive cocci are the primary cause of surgical site infections of the spine. Staphylococcus aureus, Staphylococcus epidermidis and β hemolytic Streptococci are the main bacteria that are found in cases of postoperative spinal infection. Of these, S. aureus accounts for up to 60% of surgical site infections.²³³ Following this, gram negative bacteria are the next most common bacterial causes of infection. These include Klebsiella pneumoniae, Escheria coli, Pseudomonas aeruginosa and the proteus species. Patients with a known history of drug abuse are at higher incidence of infection with gram negative rods.²²⁸ Propionibacterium acnes and diptheroids are also known causes of chronic or delayed infections.^220,234 These are commonly found in the microflora of the skin leading some to believe that prolonged postoperative drainage is a risk factor in the development of delayed postoperative spine infections.²³⁵ In a study by Koutsoumbelis et. al, 34% of positive cultures revealed methicillin resistant staphylococcus aureus.²³⁶ Incidence rates with MRSA as the concomitant organism can be correlated with risk factors such as previous hospitalization, intensive care unit stay, indwelling catheters, prolonged antibiotic therapy, advanced age and exposure to patients colonized or infected with MRSA.²³⁷

Risk factors

Modifiable and non-modifiable risk factors have been shown to correlate with surgical site spinal infections. Some of these risk factors include insulin dependent diabetes,²³⁸ history of weight loss before surgery,²³⁹ disseminated malignance or operating through irradiated skin,^221,233 chronic steroid use,²⁴⁰ anemia,^221,241 obesity, tobacco use,²³⁹ and recent epidural steroid injections.^242–245 The presence of instrumentation and a history of smoking have also been shown to increase risk of infection. Longer postoperative stays have been shown to increase infection rates by as much as 50%.²²¹

Operation and disease specific risk factors also carry the potential to increase the incidence of surgical site infections. Among these are operations involving the sacrum, long fusion constructs,²⁴⁰ operative time greater than three hours,²²¹ revision surgery,²⁴⁶ intraoperative dural tear²⁴⁷ and neuromuscular disease. Other technical factors associated with higher infection rates include inattention to aseptic technique, crowding and excessive movement in the operation room, and colonization of the members of the operating team.²⁴⁸ Careful perioperative planning can keep modifiable risk factors to a minimum and lead to lower infection rates.

Along with the aforementioned, recent epidural steroid injections have been shown to increase the chances of contracting postoperative spinal infections.^244,249It was found that timing of epidural steroid injections plays a role in the risk of attaining a postoperative infection. In a retrospective database analysis performed by Cancienne et al., 300,000 patients were divided into four cohorts to assess risk of infection post epidural steroid injection. These consisted of a control group of patients who underwent posterior cervical fusion (PCF) or anterior cervical discectomy and fusion (ACDF) without prior cervical epidural steroid injection (CESI) and three cohorts who underwent PCF or ACDF with prior CESI within 3 months, 3 to 6 months and 6 to 12 months. It was concluded that patients who underwent CESI within 6 months of PCF had significantly increased rates of postoperative infection. Along with this, patients who underwent CESI within 3 months of ACDF were shown to be independently associated with significantly increased rates of postoperative infection.²⁵⁰

Prevention

Preoperatively prophylactic antibiotics have proven effective in minimizing surgical site infections. First generation cephalosporins are typically used and most effective in preventing a postoperative infection from occurring. Other antibiotics, if the patient is allergic to penicillins, have proven effective including vancomycin, clindamycin and ciprofloxacin.^{220,221,245,251,252} In a study by Keller and Pappas, infection rates have decreased from 2.7% to 0% as a result of prophylactic antibiotics.²⁵³ In another study, postoperative infections have decreased from 9.3% to 1% after lumbar diskectomies with the use of prophylactic antibiotics.

Povidoneiodine (Betadine) is a complex of polyvinyl pyrrilidine and triiodine ions that is widely used as an antiseptic for skin, mucous membranes and wounds. Povidoneiodine has bactericidal activity against a wide spectrum of pathogens, including methicillin-resistant Staphylococcus aureus (MRSA).^254–259 In a study by Cheng et. al. a population of four hundred and fourteen patients were randomized to two groups. In group one, 218 patients’ surgical wounds were irrigated with dilute 3.5% betadine solution. In group two, consisting of 206 patients, betadine irrigation was not performed. Perioperative management remained constant between the groups. At a mean follow up time of 15.5 months, group one did not have any wound infections. Group two had one superficial infection (0.5%) and six deep infections (2.9%). The difference between the groups was statistically significant.²⁶⁰ Taking into account the effectiveness of prophylactic antibiotics and betadine irrigation, a combination of the two may aid in decreasing the incidence of surgical site infections.

Intraoperative instilment of vancomycin powder has become widely popular among spinal surgeries as a means of preventing infection. In combination with prophylactic antibiotics, this has proven effective in decreasing the incidence and preventing surgical site infections. There are many benefits to the use of intraoperative vancomycin powder instillation such as the effective broad coverage against organisms including MRSA, ease of use and cost-effectiveness.²⁶¹ Vancomycin powder has also been shown to have poor systemic absorption allowing it to act better locally to prevent infection.²⁶² In a study performed by Molinari et. al, 1,512 patients who underwent spinal surgery had a 0.99% incidence rate of surgical site infections.²⁶³ In another study wound infection rates were decreased from 13% to 0% with the application of 1g of vancomycin powder in 110 patients after posterior spinal fusion.²⁶⁴ According to O’Neil et. al, in a study of 171 patients who underwent posterior cervical fusion, infection rates declined from 10.9% to 2.5% with application of 1g of vancomycin powder.²⁶⁴

Clinical presentation

Postoperative surgical site infections may present as a superficial or deep infection. Superficial infections involve only the dermis and subcutaneous layer. Deep infections occur beneath the lumbodorsal fascia. Superficial infections often present within the first two weeks postoperatively. Commons symptoms include tenderness to palpation, erythema, edema, drainage, low grade fever and elevated ESR levels.²³⁵

Deep infections are often delayed and cause patients greater pain than superficial infections and are generally associated with malaise, and in some cases anorexia. CRP and ESR are increased to a greater magnitude when compared to superficial infections. However, a normal white cell count and the absence of fever does exclude a deep surgical site infection.²³⁵ The presence of a neurological deficit should raise suspicion for an epidural abscess. Of epidural abscesses, 16% occur in the postoperative period.²²⁸ Significant pain with lumbar range of motion is a common finding for postoperative diskitis.²²⁷

Severe surgical site infections may cause hypotension, lethargy, confusion and other signs of sepsis. Sepsis or progressive neurologic deficits are absolute indications for emergent irrigation and debridement however they are uncommon findings.^235,229

Treatment

Treatment is selected dependent upon the type of surgical site infection as well as the timing in regards to when the infection is detected. CT guided biopsy or blood cultures may be helpful to identify the pathogen causing the infection. However, CT aspiration is only about 39% sensitive.²⁶⁵ Administration of antibiotics in a timely manner is essential to patient outcome. Conservative and surgical management both have roles in treating postoperative spinal infections. Treatment ranges from antibiotics, wound explorations, irrigation and debridement with or without instrumentation removal, and closed suction irrigation systems.

In patients undergoing conservative treatment, intravenous culture specific antibiotics should be administered for approximately 6 weeks; however, the exact length of antibiotics should be directly related to patient response. Serial clinical examination and laboratory surveillance tests with WBC count, ESR and CRP should be managed.²²⁹ In cases where antibiotic resistant organisms are involved, new classes of antibiotics such as quinupristin/dalfopristin and linezolid have proven effective against 80% of vancomycin resistant enterococci and gram positive infections.²³⁷ Along with this, wound management can also be effective in eradicating surgical site infections. If there is no improvement with antibiotic treatment or progression of symptoms, wound exploration and surgical irrigation and debridement should be considered.

Epidural abscesses may be treated with antibiotics if small in size and in the lumbar region; however, if presenting with worsening neurological symptoms, this would be an indication for surgical decompression. The surgical approach, whether anterior or posterior depends on the location of the abscess in relation to the spinal canal. Anterior abscesses may necessitate vertebral debridement, anterior graft placement and also posterior reconstruction. Long segment abscesses that are still liquid can be treated by a laminotomy at the inferior end of the abscess and irrigation of the epidural space with a fine silicon catheter.²⁴⁸

Postoperative spondylodisciitis is the most resilient surgical site infection as antibiotic therapy has poor osseous penetration. This requires long durations of antibiotic therapy with some patients being successfully treated without surgical debridement.²⁶⁶ Typically, culture specific antibiotics are given intravenously for six weeks and orally for the next six weeks. Most organisms are sensitive to cephalosporins. However, MRSA and other resistant organisms would require antibiotics like vancomycin, linezolid, piperacillin, and clindamycin.²⁴⁸ If there is no improvement with antibiotics or there is worsening of neurologic symptoms, operative intervention must be considered.

At the time of surgical debridement of a postoperative infection, instrumentation that is stable is retained if diagnosed in the early postoperative period. In one study,²²⁴ 132 postoperative spinal infections diagnosed early retained stable and replaced loose implants at debridement and reported that 76% of postoperative infections were treated successfully with only 1 debridement. A study done by Glassman, 19 instrumented patients who developed a deep infection and were treated by repeat debridement (average 4.7 procedures) successfully retained their implants and were disease free at 1 year follow up.²⁶⁷ Mok et al. states that implant preservation can be done with eradication of infection in most cases with early diagnosis, aggressive debridement and proper antibiotic therapy.²⁶⁸ There are risks of non-union and loss of correction of deformity as a result of removal of instrumentation. However, in delayed infections, instrumentation should be removed.²³⁶

Conclusion

Understanding the risk factors for a postoperative spinal infection can aid in its prevention. When possible, modifiable risk factors should be changed. Early recognition and diagnosis is the key in successfully eradicating a postoperative infection.

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