Brucellosis mainly affects the musculoskeletal system, with the spine as the most common location. Diagnosis is based on clinical symptoms, but in some cases, they may be lacking. Laboratory diagnosis is mainly made on the combination of high erythrocyte sedimentation rate (ESR) together with high levels of C-reactive protein (CRP) and leukocytosis. Blood culture is a very cost-effective investigation; plain radiographs may be useful, but magnetic resonance images (MRI) with gadolinium enhancement is the choice for diagnosing osteoarticular and spinal complications of human brucellosis. MRI diffusion-weighted imaging fast sequence is the most sensitive for differentiating acute and chronic forms of spondylodiscitis. The basis for treatment is usually the medical management. The indications for surgical treatment (endoscopy or open) are when: no microorganism has been isolated, spinal cord or dural compression is seen in MRI, or there's spinal instability or severe deformity. Open surgery is the standard: the anterior approach allows for anterior disc and bone debridement. If there is an epidural abscess or posterior elements are involved it's indicated as a posterior approach. To prevent relapses and reduce the rate of sequelae, it's necessary to have an appropriate duration of antimicrobial therapy and a timely indication to perform surgery.
- spine brucellosis
- granulomatous infection
- surgical treatment
Spondylodiscitis refers to an infection affecting the intervertebral disk, the vertebral body, or the posterior arch of the vertebra. Aetiologically, spinal infection can be classified as pyogenic, granulomatous (tuberculosis, brucellosis, or fungal infection), or parasitic. Brucellosis mainly affects the musculoskeletal system, with the spine as the most common location.
Epidemiology. Brucella, one of the world’s major zoonotic pathogens, is responsible for huge economic losses, as well as significant human morbidity in endemic areas . It is caused by an aerobic, Gram-negative rods of the genus Brucella, discovered by David Bruce in 1887 . In humans, this disease is also called Maltese fever, Bang’s disease, undulant fever, or Mediterranean fever . Human brucellosis involves an important public health problem in most developing countries including those of the Mediterranean, Balkans, the Middle East, Central Asia, and Central and South America. New foci of human brucellosis have emerged, particularly in Central Asia .
Pathogenic. Brucellosis is a systemic disease and many organ systems (nervous system, heart, skeletal system, bone marrow, etc.) may become involved following hematogenous dissemination. However, osteoarticular involvement is the most common complication of brucellosis, being reported in 10%–85% in most series . The sacroiliac joint and arthritis are generally affected in the acute form. However the spine is usually affected in the subacute and chronic forms of this disease. The sacroiliac joint involvement and arthritis occur in patients under 30 years old, whereas the spine affectation is characteristic of older patients . In the musculoskeletal system the spine is the most often affected location [7, 8]. The incidence of spinal involvement can be quite different, from 2%–54%, it depends on the type of population you study . The radiographic changes will appear between the third to the twelfth week of the start of clinical symptoms . The L4-L5 and L5-S1 junctions are the most frequent locations affected .
Clinical syndrome. Brucellosis is an acute (25%–77%), subacute (12.5%–59%), or chronic (5%–27.5%) illness that presents with a spectrum of nonspecific signs and symptoms. The disease is severely disabling with fever, sweating, fatigue, weight loss, headache, and joint pain that can persist for weeks to months. Spinal manifestations tend to occur during chronic infections [12, 13]. Clinical presentation varies widely  and approximately one-third of the patients have a more fulminant illness with acute onset of systemic toxicity . The earliest sign of spondylitis is localized spine pain , since some degree of neurologic compromise may occur between 10%–43% of those with spondylitis , and in 10%–20% a paraspinal abscess develops. In a multicenter prospective study of 593 patients with brucellosis , 9.7% had spondylitis; neurologic deficits occurred in five (71%) of the patients with cervical spondylitis, two (11%) of the patients presented thoracic involvement, and nine (21%) developed lumbar disease. Paraspinal and epidural abscesses were more frequent in patients with cervical and thoracic disease; the worst prognosis was for those having cervical spine involvement. Complications of spinal brucellosis, with affectation of neighboring vertebrae with paraspinal, psoas, or epidural abscesses, with or without neurological affectation is uncommon; however, several series have published cases of complicated spinal brucellosis [19–22], although possible multilevel involvement may occur .
Diagnosis. It is not always easy. Suspected diagnosis of spondylodiscitis is based on clinical symptoms (pain, fever, and deformity), although, in some cases, they may be lacking. Patients complaining of back pain, particularly in endemic areas, should be accurately investigated. Laboratory diagnosis is mainly made in the presence of combination of high erythrocyte sedimentation rate (ESR) together with high levels of C-reactive protein (CRP) and, less useful, leukocytosis. Blood cultures are positive in less than half the cases overall but indeed in 70% of patients with acute B. melitensis infection. An agglutination reaction with a Brucella antibody titer of 1 : 160 or greater is presumptive evidence of infection, but an increasing titer is a more helpful sign of active infection [16, 17].
The diagnostic confirmation of spinal spondylitic granulomatous can be done by the polymerase chain reaction (PCR). If we have a case of prior antibiotic used or the presence of fastidious microorganisms, the molecular diagnostic can be done using broad-range 16S rDNA PCR . By amplification of the mec A gene, doing species-specific PCR, especially targeting the Staphylococcus aureus, the sensitivity can increase, providing methicillin susceptibility . But these methods are not completely unerring by themselves; in fact, nowadays, they are considered as an important complementary to standard cultures particularly those harvested through image-guided surgery . Blood culture is a very cost-effective investigation. Plain radiographs may be useful; however, even large destructive spondylodiscitis may go undetected on X-rays as changes take several months to appear. Furthermore, usually in more aged patients, it may be difficult to distinguish between infection destruction and degenerative changes. The first radiological sign that we will find is osteoporosis of the affected vertebral body and erosion of the anterior-superior endplate, so-called Pons' sign, also a vacuum phenomenon may be observed in the anterior part of the disc (accumulation of gas with the crevices of the intervertebral or adjacent discs). The appearance of destructive changes on plain radiographs appears from the third month of the disease.
Radionuclide tests are currently less used. If magnetic resonance images (MRI) cannot distinguish among degenerative changes and infection, the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) can be useful .The most useful image test, with the higher sensitivity and specificity for the diagnosis of spondylodiscitis, is MRI with gadolinium enhancement, which also provides information on anatomy . CT-scan is useful in assessing the bone destruction and also for surgical planning, as well as contributes greatly in the CT-guided needle percutaneous biopsy . MRI is the method of choice for diagnosing osteoarticular and spinal human brucellosis and its complications, especially during the early phase [29, 30]. It has been published  that diffusion-weighted imaging fast sequence is the most sensitive diagnosis tool for differentiating between acute and chronic forms of spondylodiscitis.
Sometimes diagnosis of brucellar spondylodiscitis becomes a major task as clinical findings are usually nonspecific and radiological features may mimic those of other bacterial, fungical, inflammatory, and neoplastic diseases. Likewise, it is very common to confuse spinal brucellosis with tuberculosis.
Differential diagnosis must be performed with tuberculous spondylitis, salmonella spondylitis, pyogenic spondylitis, disc herniation, and metastatic lesions [32–34]. The radiologic findings for tuberculous and brucellar spondylodiscitis are similar, so serologic testing for brucellosis is necessary in such cases ; and also the MRI findings are different as tuberculosis produces more severe changes with more deformity and abscess formation . There are also differences regarding the involvement of the intervertebral disc spaces, whereas in brucellar spondylodiscitis intervertebral discs are narrowed, in metastatic diseases or in tuberculous spondylitis intervertebral discs are rarely affected. However, in brucellar spondylodiscitis the affectation of the posterior elements is very uncommon, while it may be frequently encountered in metastatic disease and tuberculosis spondylodiscitis. Paravertebral and epidural abscess formation and spinal cord and root compression are considered very rare findings in brucellar spondylodiscitis and are generally considered to be findings for tuberculosis and pyogenic spondylodiscitis.
Findings characteristic of MRI for brucellar spondylitis  are: vertebral body signal changes without morphologic changes, marked signal increase in the intervertebral disc on T2-weighted and contrast-enhanced sequences, vertebral endplate defects mimicking Schmorl's nodules, obliteration of muscle fat borders, moderate amount of paraspinal granulation tissue, and gas accumulation in the disc space and facet joint involvement. Nevertheless, some of these signs, such as the presence of gas, can also be present in pyogenic infections. In any case, the most useful method for detecting the presence and extension of brucellar spondylitis is the MRI, particularly using the fat-suppression technique with contrast. Even in extensive cases, vertebral collapse and gibbus deformity are rare findings, and the vertebral body is usually morphologically intact (Figures 1, 2, 3).
Biopsy is necessary to confirm the diagnosis in only 5% of the cases, in contrast to pyogenic and tuberculosis spondylitis .
The treatment of spinal brucellosis is mainly medical. The surgical intervention is reserved for biopsy, severe neurological impairment, and rarely for spinal stabilization.
The combination of tetracycline (tetracycline, 500 mg every 6 hours given orally or doxycycline, 100 mg every 12 hours) for 6 weeks together with an aminoglycoside (preferably, streptomycin, 1 g/day intramuscularly for 2–3 weeks or gentamicin 5 mg/kg/day intravenously or intramuscularly for 7–10 days) is the current first line therapy for brucellosis as recommended by the World Health Organization. The combination of rifampicine (600–900 mg/day orally administrated) and doxycycline (100 mg every 12 hours orally administrated) for 6 weeks is suggested as the principal alternative therapy. In spinal brucellosis, it is noted that the same regimens can be given, but the duration of therapy should be longer. A combination of doxycycline (200 mg/day, for at least 12 weeks) with streptomycin (1 g/day, for 2 or 3 weeks) is still the first-line antimicrobial regimen in spinal brucellosis. For a long time Doxycycline + rifampin or co-trimoxazole + rifampin or ciprofloxacin + rifampin or ciprofloxacin + streptomycin could be used as an alternative when adverse reactions or contraindications (ototoxicity, nephrotoxicity, pregnancy, lactation, etc.) are present . The combination of doxycycline and streptomycin has been used for a long time for complications and severe disease . However, therapeutic failure and relapse are still reported with this regimen . Response to treatment is monitored with repeated agglutination tests. Lifeso and colleagues  recommend continuing antibiotic therapy until the agglutination test titer is equal or less than 1 : 160 and there is clinical and radiographic evidence of disease resolution. Relapses seldom occur in patients who do not receive appropriate treatment and are often the result of focal suppurative complications such as spondylitis.
Conservative treatment is indicate in patients without spine instability or neurological deficits and with high surgical risk . The doubt may arise in case of minor neurological deficits, for that some authors  prefer conservative treatment if there is no spinal instability as neurological symptoms will be improved with antibiotics. It is of paramount importance to achieve proper immobilization of the affected spinal segment; orthoses could be used for that purpose and in same instances, protected bed rest, although home confinement now is being abandoned .
If after 4 to 6 weeks of conservative treatment there are signs of spine instability, progressive deformity, or no clinical improvement, surgical treatment must be the choice.
On the other hand, early surgical treatment should be performed in the presence of sepsis or neurological deficits. Patients with spinal epidural abscess have high rates of morbidity and mortality, therefore, in these urgent surgical cases surgical treatment is essential .
Surgery is indicated in the presence of spinal instability, cord compression or radiculopathy . Whenever a root, spinal cord, or dura mater compression is seen on MRI (epidural abscess with an anterior longitudinal ligament bulge), the patient must be taken to the theatre . A clear indication for surgical treatment is spinal instability due to a great deformity or due to bone destruction. In case of an anterior abscess larger than 2.5 cm, a surgical evacuation must be carried out. Also, if there is concomitant vertebral body destruction, bone debridement with subsequent anterior body reconstruction must done, too. There are other indications for surgery such as: unsuccessful medical treatment, negative biopsy or lingering pain . The main role for surgery is to perform a debridement and biopsy for culture, and also if there is biomechanical instability a stabilizing surgery will be performed at this moment or at another time .
Nowadays, there are two different surgical treatment options: less invasive or classic open surgery.
Less invasive techniques can facilitate debridement  (e.g., endoscopy, CT-scan percutaneous-guided surgery) and reconstruction (posterior percutaneous instrumentation is already regularly used in patients undergoing a double approach)  (Figure 4). Thoracoscopy has very much changed the philosophy of the current surgical treatment for the spondylodiscitic thoracic spine.
Open surgery can use any standard approach (anterior, posterior, or combined). The choice will depend on the location of the infection, the degree of bone destruction, and the presence of neurological deficits.
Thus, open surgery can be either anterior, posterior, or a combination of both, performed either in one or two stages. Usually, open surgery consists of an anterior approach and a secondary posterior approach. During the anterior approach, full disc and affected vertebral bone sequestra must be performed, followed by inserting a tricortical bone graft piece in between the above and below vertebral bodies for anterior vertebral bodies bridging. Ostheosynthesis through the combined posterior approach (in epidural abscess, important kyphosis and/or instability) with pedicular instrumentation is advisable to complement anterior debridement and fusion.
The anterior approach is the standard for anterior vertebral body debridement and stabilization. Most authors agree with the conclusion of the Medical Research Council that the Hong Kong procedure  of anterior radical debridement and reconstruction of the large anterior gap with strut graft is superior to any other procedure, and must be combined with posterior stabilization. Some authors prefer to start with a posterior approach for mechanical stabilization followed by radical anterior debridement; this has the advantage of having a very stable spine for radical anterior debridement [52, 53] (Figure 5).
In many series, radical debridement and anterior insertion is followed by the insertion of a titanium cage, filled with autogenous bone graft, together with a posterior less invasive approach for pedicle screw fixation in order to eliminate posterior soft tissue injury, preserve blood supply, and reduce surgical time, blood loss, and surgical complications . Interbody cages have the function of providing an anterior support to compression forces, without the morbidity of tricortical harvesting . Though, if we do a literature review, it seems that interbody cages have not completely resolved the complications and problems of interbody spinal fusions [56, 57].
The posterior approach is the first choice in cases of epidural abscess at the lumbar level in order to perform proper drainage, followed by pedicular instrumentation. If only one level is approached, instrumentation can be avoided. Large multilevel laminectomies without instrumentation are contraindicated, as it increases instability that already exists, provoked by the destruction of the anterior spine; it therefore, may result in paraplegia. Thus, in cases of substantial anterior destruction, collapse, spinal deformity, and when great debridement is recommended, an anterior approach must be the choice [58, 59]. A two-stage (posterior and anterior) surgical treatment for pyogenic or granulomatous spondylitis (first, the placement of posterior instrumentation and then anterior debridement and bone graft) provided satisfactory results; however, should kyphosis exists, changes in sagittal alignment may be difficult to be corrected .
In smaller defects, autograft is usually harvested from the iliac crest and ribs, and for larger bone deficits the choice is fibular graft . In severe cases, only fibular grafts can allow a buttressing support, with a tension band principle if a concurrent pedicular instrumentation is also performed . Louw  reported high fusion rates with vascularized rib grafts for stabilization and also good results with fibular graft for large defects used with stabilization by a posterior instrumentation. The use of BMPs combined with structural bone graft for spinal fusion has been claimed to provide good results and improve posterior fusion rates in pyogenic vertebral osteomyelitis after a 11–30 months follow up , though more studies are needed with longer follow-up.
According to the level of infection, surgical planning will be different. To the cervical spine, upper C1-C2 spine can be approached by a transpolar access; a posterior approach for occiput-C2 fusion may be necessary whenever a major instability is observed. The C3-C7 segment can be approached either anteriorly, posteriorly, or both, depending on abscess localization, instability, and fusion technique for this segment. Usually an anterior approach is recommended for debridement, decompression (eventual corpectomy), and fusion with bone graft associated with anterior plate stabilization (Figure 6). If it is a multilevel intervention, this must be complemented with pedicular instrumentation .
The thoracic spine can be approached either through an anterior transthoracic, posterior costotransversectomy, or an extra pleural anterolateral approach. Transthoracic approach give better results than lateral costotrasversectomy, for debridement, fusion rates, and mortality. At this spine level, it is recommended to use autograft and pedicular instrumentation.
The lumbar spine retroperitoneal approach is very useful, but opening the peritoneum must be avoided as intraperitoneal complications can occur. Debridement, abscesses drainage, and anterior instrumentation are easily performed by this approach.
Despite a properly treatment, sequelae, such as back pain or residual neurological symptoms, will persist due to degenerative changes secondary to destruction and instability caused by the infectious process.
In order to prevent relapses and reduce the rate of sequelae, it is necessary that an appropriate duration of antimicrobial therapy (antimicrobial treatment should be prolonged in complicated spinal forms of brucellosis ) and a timely indication to perform surgery, if necessary.
Boschiroli ML, Foulongue V, O´Callaghan D. Brucellosis: A worldwide zoonosis. Curr Opin Microbiol. 2001;4:58-64.
Bruce D. Note on the discovery of a microorganism in Malta fever. Practitioner. 1887;39:161-70.
Galinska EM, Zagórski J. Brucellosis in humans—etiology, diagnostics, clinical forms. Ann Agric Environ Med. 2013;20:233-8.
Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis. 2006;6:91-9.
Doganay M, Aygen B. Human brucellosis: An overview. Int J Infect Dis. 2003;7:173-82.
Chelli Bouaziz M, Ladeb MF, Chakroun M, Chaabane S. Spinal brucellosis: A review. Skeletal Radiol. 2008;37:785-90.
Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. Lancet Infect Dis. 2007;7:775-86.
Franco MP, Mulder M, Smits HL. Persistence and relapse in brucellosis and need for improved treatment. Trans R Soc Trop Med Hyg. 2007;101:854-55.
Mousa AR, Muhtaseb SA, Almudallal DS, Khodeir SM, Marafie AA. Osteoarthicular complications of brucellosis: A study of 169 cases. Rev Infect Dis. 1987;9:531-43.
Geyik MF, Gu°r A, Nas K, Cevik R, Sarac J, Dikici B, et al. Musculoskeletal involvement in brucellosis in different age groups: A study of 195 cases. Swiss Med Wkly. 2002;132:98-105.
Pourbagher A, Pourbagher MA, Savas L, Turunc T, Demiroglu YZ, Erol I, et al. Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement. AJR Am J Roentgenol. 2006;187:873-80.
Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med. 2005;352:2325-36.
Pappas G, Akritidis N, Tsianos E. Effective treatments in the management of brucellosis. Expert Opin Pharmacother. 2005;6:201-9.
Zribi MA, Ammari L, Masmoudi A, Tiouiri H, Fendri C. Clinical manifestations, complications and treatment of brucellosis: 45-patient study. Pathol Biol (Paris). 2009;57:349-52.
Young EJ: Brucella specia. 1995 Churchill Livingstone New York 2053-2060.
Keenan JD, Metz CW Jr. Brucella spondylitis. A brief review and case report. Clin Orthop Relat Res. 1972;82:87-91.
Lifeso RM, Harder E, McCorkell SJ. Spinal brucellosis. J Bone Joint Surg Br. 1985;67:345-51.
Colmenero JD, Cisneros JM, Orjuela DL, et al. Clinical course and prognosis of Brucella spondylitis. Infection. 1992;20:38-42.
Ulu-Kilic A, Sayar MS, Tütüncü E, Sezen F, Sencan I. Complicated brucellar spondylodiscitis: Experience from an endemic area. Rheumatol Int. 2013;33:2909-12.
Colmenero JD, Ruiz-Mesa JD, Plata A, et al. Clinical findings, therapeutic approach, and outcome of brucellar vertebral osteomyelitis. Clin Infect Dis. 2008;46:426-33.
Buzgan T, Karahocagil MK, Irmak H, et al. Clinical manifestations and complications in 1028 cases of brucellosis: A retrospective evaluation and review of the literature. Int J Infect Dis. 2010;14: e469-78.
Ates O, Cayli SR, Kocak A, Kutlu R, Onal RE, Tekiner A. Spinal epidural abscess caused by brucellosis two case reports. Neurol Med Chir (Tokyo). 2005;45:66-70.
Bouaziz MC, Bougamra I, Kaffel D, Hamdi W, Ghannouchi M, Kchir MM. Noncontiguous multifocal spondylitis: An exceptional presentation of spinal brucellosis. Tunis Med. 2010;88:280-84.
Sontakke S, Cadenas MB, Maggi RG, Diniz PP, Breitschwerdt EB. Use of broad range16S rDNA PCR in clinical microbiology. J Microbiol Methods. 2009;76(3):217-25.
Gouliouris T, Aliyu SN, Brown MN. Spondylodiscitis: Update on diagnosis and management. J Antimicrob Chemother. 2010;65(Suppl 3):11-24.
Stumpe KD, Zanetti M, Weishaupt D, Hodler J, Boos N, Von Schulthess GK. FDG positron emission tomography for differentiation of degenerative and infectious endplate abnormalities in the lumbar spine detected on MR imaging. AJR Am J Roentgenol. 2002;179:115-7.
Modic MT, Feiglin DH, Piraino DW, Boumphrey F, Weinstein MA, Duchesneau PM, Rehm S. Vertebral osteomyelitis: Assessment using MR. Radiology. 1985;157:157-66.
Michel SC, Pfirrmann CW, Boos N, Hodler J. CT-guided core biopsy of subchondral bone and intervertebral space in suspected spondylodiskitis. AJR Am J Roentgenol. 2006;186:977-80.
Yang X, Zhang Q, Guo X. Value of magnetic resonance imaging in brucellar spondylodiscitis. Radiol Med. 2014 Dec;119:928-33.
Bozgeyik Z, Aglamis S, Bozdag PG, Denk A. Magnetic resonance imaging findings of musculoskeletal brucellosis. Clin Imaging. 2014;38:719-23.
Oztekin O, Calli C, Adibelli Z, Kitis O, Eren C, Altinok T. Brucellar spondylodiscitis: Magnetic resonance imaging features with conventional sequences and diffusion-weighted imaging. Radiol Med. 2010;115:794-803.
Tali ET. Spinal infections. Eur J Radiol. 2004;50:120-33.
Turunc T, Demiroglu YZ, Uncu H, Colakoglu S, Arslan H. A comparative analysis of tuberculous, brucellar and pyogenic spontaneous spondylodiscitis patients. J Infect. 2007;55:158-63.
Ozaksoy D, Yucesoy K, Yucesoy M, Kovanlıkaya I, Yuce A, Naderi S. Brucellar spondylitis: MRI findings. Eur Spine J. 2001;10:529-33.
Sharif HS, Aideyan OA, Clark DC, et al. Brucellar and tuberculous spondylitis: Comparative imaging features. Radiology. 1989;171:419-425.
Alp E, Doganay M. Current therapeutic strategy in spinal brucellosis. Int J Infect Dis. 2008;12:573-7.
Colmenero JD, Jimenez-Mejias ME, Sanchez-Lora FJ, et al. Pyogenic, tuberculous, and brucellar vertebral osteomyelitis: A descriptive and comparative study of 219 cases. Ann Rheum Dis. 1997;56:709-15.
Corbel MJ. Brucellosis in humans and animals. Geneva, Switzerland: World Health Organization Publications, 2006.
Alavi SM, Alavi L. Treatment of brucellosis: A systematic review of studies in recent twenty years. Caspian J Intern Med. 2013;4:636-41.
Aygen B, Doganay M, Sumerkan B, Yildiz O, Kayabas U. Clinical manifestations, complications and treatment of brucellosis: A retrospective evaluation of 480 patients. Med Mal Infect. 2002;32:485-93.
Sobottke R, Seifert H, Fätkenheuer G, Schmidt M, et al. Current diagnosis and treatment of spondylodiscitis. Dtsch Arztebl Int. 2008;105:181-87.
Duarte RM, Vaccaro AR. Spinal infection: State of the art and management algorithm. Eur Spine J. 2013;22:2787-99.
Cramer J, Haase N, Behre I, Ostermann PAW. Spondylitis und Spondylodiszitis. Trauma und Berufskrankheit. 2003;5:336-341.
Lu CH, Chang WN, Lui CC, Lee PY, Chang HW. Adult spinal epidural abscess: Clinical features and prognostic factors. Clin Neurol Neurosurg. 2002;104:306-10.
Nas K, Gur A, Kemaloglu MS, et al. Management of spinal brucellosis and outcome of rehabilitation. Spinal Cord. 2001;39:223-7.
Darouiche RO. Spinal epidural abscess. N Engl J Med. 2006;355:2012-20.
Chen WH, Jiang LS, Dai LY. Surgical treatment of pyogenic vertebral osteomyelitis with spinal instrumentation. Eur Spine J. 2007;16:1307-16.
Guerado E, Cerván AM. Surgical treatment of spondylodiscitis. An update. Int Orthop. 2012;36:413-20.
Yang SC, Fu TS, Chen LH, Chen WJ, Tu YK. Identifying pathogens of spondylodiscitis: Percutaneous endoscopy or CT-guided biopsy. Clin Orthop Relat Res. 2008;466:3086-92.
Mückley T, Schütz T, Schmidt MH, Potulski M, Bühren V, Beisse R. The role of thoracoscopic spinal surgery in the management of pyogenic vertebral osteomyelitis. Spine. 2004;29:E227-33.
Five-year assessments of controlled trials of ambulatory treatment, debridement and anterior spinal fusion in the management of the tuberculosis of the spine. Studies in Vulawayo (Rhodesia) and in Hong Kong. Sixth report of the Medical Research Council Working Party on Tuberculosis of the spine. J Bone Joint Surg Br. 1978;60:163-77.
Moon MS, Woo YK, Lee KS, Ha KY, Kim SS, Sun DH. Posterior instrumentation and anterior interbody fusion for tuberculous kyphosis of dorsal and lumbar spine. Spine. 1995;20:1910-68.
Turgut M. Spinal tuberculosis (Potts disease): Its clinical presentation, surgical management and outcome: A survey study on 694 patients. Neurosurg Rev. 2001;24:8-13.
Korovessis P, Petsinis G, Koureas G, Iliopoulos P, Zacharatos S. Anterior surgery with insertion of titanium mesh cage and posterior instrumented fusion performed sequentially on the same day under one anesthesia for septic spondylitis of thoracolumbar spine: Is the use of titanium mesh cages safe? Spine. 2006;31:1014-9.
Hee HT, Majd ME, Holt RT, Pienkowski D. Better treatment of vertebral osteomyelitis using posterior stabilization and titanium mesh cages. J Spinal Disord Tech. 2002;15:149-56;discussion 156.
Smith AJ, Arginteanu M, Moore F, Steinberger A, Camins M. Increased incidence of cage migration and nonunion in instrumented transforaminal lumbar interbody fusion with bioabsorbable cages. J Neurosurg Spine. 2010;13:388-93.
Reinhold M, Knop C, Beisse R, Audigé L, Kandziora F, Pizanis A, et al. Operative treatment of 733 patients with acute thoracolumbar spinal injuries: comprehensive results from the second, prospective, Internet-based multicenter study of the Spine Study Group of the German Association of Trauma Surgery. Eur Spine J. 2010; 19:1657-76
Zarghooni K, et al. Treatment of spondylodiscitis. Int Orthop. 2012;36:405-11
Linhardt O, Matussek J, Refior HJ, Krödel A. Long-term results of ventro-dorsal versus ventral instrumentation fusion in the treatment of spondylitis. Int Orthop. 2007;31:113-9
Fukuta S1, Miyamoto K, Masuda T, Hosoe H, Kodama H, Nishimoto H, Sakaeda H, Shimizu K. Two-stage (posterior and anterior) surgical treatment using posterior spinal instrumentation for pyogenic and tuberculotic spondylitis. Spine (Phila Pa 1976). 2003 Aug 1;28:E302-8.
Hirakawa A, Miyamoto K, Masuda T, Fukuta S, Hosoe H, Iinuma N, et al. Surgical outcome of 2-stage (posterior and anterior) surgical treatment using spinal instrumentation for tuberculous spondylitis. Spinal Disord Tech. 2010 Apr;23:133-8.
Guerado E, Fuerstenberg CH. What bone graft substitutes should we use in post-traumatic spinal fusion? Injury Suppl. 2011;2:S64–S71.
Louw JA. Spinal tuberculosis with neurologic deficit: Treatment with vascularized rib grafts, posterior osteotomies and fusion. J Bone Joint Surg Br. 1986;72:686-93.
Allen RT, Lee YP, Stimson E, Garfin SR. Bone morphogenetic protein-2 (BMP-2) in the treatment of pyogenic vertebral osteomyelitis. Spine. 2007;32:2996-3006.
Pola E, Rossi B, Nasto LA, Colangelo D, Logroscino CA. Surgical treatment of tuberculous spondylodiscitis. Eur Rev Med Pharmacol Sci. 2012;16 Suppl 2:79-85.
Ulu-Kilic A, Karakas A, Erdem H, Turker T, Inal AS, Ak O, et al. Update on treatment options for spinal brucellosis. Clin Microbiol Infect. 2014;20:O75-82.