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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 1  |  Page : 75-82

Clinical profile, diagnosis, treatment, and outcome of patients with tubercular versus nontubercular causes of spine involvement: A retrospective cohort study from India


1 Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education; Manipal Center for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Orthopaedics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
4 Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
5 Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
6 Department of Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran; Department of Medicine, Alfaisal University, Riyadh, Saudi Arabia

Date of Submission07-Dec-2021
Date of Decision29-Dec-2021
Date of Acceptance28-Jan-2022
Date of Web Publication12-Mar-2022

Correspondence Address:
Kavitha Saravu
Professor and Head, Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_243_21

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  Abstract 


Background: In tuberculosis (TB) endemic areas, other pyogenic causes of spine involvement may be missed. The study aimed to describe TB and non-TB causes of spine involvement and identify features that can help in differentiating them. Methods: A retrospective cohort study was conducted to screen the clinical records of all admitted patients (Kasturba Hospital, Manipal) in 2018–20 for a diagnosis of spondylitis and/or sacroiliitis. The clinical features, radiological findings, laboratory parameters, treatment details, and outcomes were compared among those diagnosed with confirmed TB, confirmed brucellosis, or confirmed pyogenic infection. A scoring system was also developed to differentiate spondylodiscitis due to tuberculous and pyogenic causes. The qualitative variables were compared using the Chi-square test, while quantitative variables were compared using the one-way analysis of variance test. Results: Of 120 patients with spine infections, a total of 85 patients were confirmed with the microbiological diagnosis of interest. Involvement of the thoracic spine, longer duration of illness, and caseous granulomatous reaction on histopathology was more common in TB patients. Male gender, involvement of lumbar vertebra, and neutrophilic infiltrate on histopathology were more common in brucellosis patients. Male gender, diabetes mellitus, involvement of lumbar vertebra, neutrophilic infiltrate on histopathology, leukocytosis, and increased C-reactive protein were more commonly seen in patients with pyogenic infection. The scoring system had a sensitivity and specificity of 75% and 91%, respectively, when used to differentiate TB from pyogenic infection. Conclusions: In resource-limited settings, suggestive findings can be used to decide empiric therapy.

Keywords: Brucellosis, Pott's spine, spondylitis, vertebral osteomyelitis


How to cite this article:
Gupta N, Bhat SN, Reddysetti S, Afees Ahamed M A, Jose D, Sarvepalli AS, Joylin S, Godkhindi VM, Rabaan AA, Saravu K. Clinical profile, diagnosis, treatment, and outcome of patients with tubercular versus nontubercular causes of spine involvement: A retrospective cohort study from India. Int J Mycobacteriol 2022;11:75-82

How to cite this URL:
Gupta N, Bhat SN, Reddysetti S, Afees Ahamed M A, Jose D, Sarvepalli AS, Joylin S, Godkhindi VM, Rabaan AA, Saravu K. Clinical profile, diagnosis, treatment, and outcome of patients with tubercular versus nontubercular causes of spine involvement: A retrospective cohort study from India. Int J Mycobacteriol [serial online] 2022 [cited 2022 May 25];11:75-82. Available from: https://www.ijmyco.org/text.asp?2022/11/1/75/339513




  Introduction Top


Infectious involvement of the spine is associated with significant long-term neurological morbidity if not diagnosed early.[1] However, since most patients present insidiously, it is easy to miss them early in the stage of illness, and many of these patients are labeled with degenerative disease. In a study of 101 cases of tuberculous and pyogenic spondylodiscitis, 34% of the patients were misdiagnosed initially, and an average delay in diagnosis of 2.6 months was observed.[2] Several other studies have described significant delays in the diagnosis of vertebral osteomyelitis.[3],[4],[5] In addition, because the microbiological diagnosis often requires invasive procedures, many patients are started on empirical therapies in resource-limited settings.

Spinal tuberculosis (TB) is one of the oldest diseases known to humankind and accounts for 1%–2% of all cases of TB.[6] In the Indian subcontinent, TB is the most common cause of spine involvement. Consequently, many patients receive empirical anti-tubercular therapy (ATT). However, it is important to note that bacterial infections such as  Brucellosis More Details, Staphylococcus spp., Streptococcus spp., and  Escherichia More Details coli can have similar manifestations and can be missed when patients are started on empiric ATT. Therefore, it is vital to understand the frequency of different microorganisms causing spondylitis in tropical countries so that the practice of empirical ATT can be justified or refuted. Furthermore, since many resource-limited settings, may not have facilities to obtain invasive tissue samples, identifying clinical and laboratory clues for diagnosis can help in tailoring the empiric regimen in resource-limited settings. The study, therefore, aimed to identify TB and non-TB causes of spine involvement and identify features that can help in differentiating them.


  Methods Top


Study design and population

The in-patient and outpatient records were screened for patients of all ages and either gender admitted to Kasturba Hospital, Manipal, Karnataka, between January 1 2018 and January 1, 2020, with a diagnosis of vertebral osteomyelitis or sacroiliitis. Those patients where suspicion of infectious involvement of the spine was made were included for the screening process. Postoperative spine infections or infections related to implants/prostheses were excluded.

Ethical issue and patient consent

The study was approved by the institutional ethics committee (IEC number 470/2020, Date: October 20, 2021). Since this was a retrospective review of charts, individual patient consent was not required.

Routine workflow

The routine workflow of patients with infectious spine involvement in our hospital is as follows. Patients are initially admitted under a spine specialist. The patient is clinically evaluated for the extent of spine involvement. Magnetic resonance imaging (MRI) of the affected spine segment is undertaken. In those patients with financial constraints, standard anteroposterior and lateral radiographs are done instead. Complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), and blood cultures are sent at the baseline for the admitted patients. Blood culture is routinely incubated for an extended duration for brucellosis. A standard agglutination test (SAT) for brucellosis is sent if there is a suspicion of brucellosis and no financial constraints. A repeat serology is done in some patients at the physician's discretion. Surgery (decompression or debridement with/without spinal stabilization) is planned for those patients who present with neurological deficits or have a rapidly progressive course. The judgment of the treating team and willingness of the patients to undergo surgery are also taken into account. In those patients where a diagnosis is not established, and surgery is not indicated, a closed biopsy is preferred in our center. All intra-operative samples are sent for bacterial cultures, GeneXpert, and histopathology. The medical management is undertaken in consultation with infectious disease specialists. Those patients diagnosed with confirmed TB are treated with standard ATT consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. The minimum duration recommended by the national guideline is 15 months, but the final duration is decided based on clinical and biochemical responses. Those patients with confirmed brucellosis are treated with doxycycline, rifampicin, and gentamicin (first 2 weeks) for a total duration of 12 weeks. Those patients with confirmed pyogenic spondylitis are treated with a variable duration of intravenous (IV) therapy followed by oral therapy. The transition from IV to oral and final duration of therapy is decided based on clinical improvement.

Definitions

A patient was diagnosed as probable TB spondylitis if all three criteria were met: (i) Presence of relevant clinical findings, (ii) suspicion of TB on the radiology or histopathology report, and (iii) a working diagnosis of TB and initiation of anti-tubercular therapy (ATT) by the treating team. Of those with probable TB, those with a positive GeneXpert, or culture positivity from the tissue sample obtained from the involved site were classified as confirmed TB. A patient was defined as probable bacterial spondylitis if all three criteria were met: (i) Presence of relevant clinical findings, (ii) suspicion of bacterial infection on the radiology or histopathology report, and (iii) a working diagnosis of bacterial infection and initiation of antibiotics by the treating team. Those with culture positivity for  Brucella More Details spp. in blood or involved sites were considered as confirmed brucellosis. Those with negative cultures were also deemed confirmed brucellosis if a four-fold rise or fall in titer on the SAT was demonstrated. Those with culture positivity for single bacterial species (Staphylococcus spp., Streptococcus spp., and E. coli) in blood or involved sites were diagnosed as confirmed pyogenic infection.

Data collection

The baseline, demographic features, the pattern of joint involvement, laboratory parameters, treatment details (medical and surgical), and outcome were recorded for the enrolled patients. The clinical features, radiological findings, and laboratory parameters during the first admission were collected. History of fever and weight loss, features of radiculopathy (back pain radiating to limbs with/without paraesthesia), paraparesis (weakness of lower limbs) were recorded. The type (cervical, thoracic, lumbar, sacral) and the number of vertebrae along with paravertebral or epidural involvement (abscess or phlegmon or soft-tissue enhancement) on imaging were also recorded. The records of all enrolled patients were reviewed for clinical/radiological response on follow-up. In addition, the treatment duration of those who had completed treatment at the last follow-up was recorded. The details were recorded in an excel workbook.

Data analysis

Qualitative variables were summarized as frequency and percentage, while quantitative variables were summarised as mean ± standard deviation or median (interquartile range). The qualitative variables of patients with confirmed TB confirmed brucellosis and confirmed pyogenic infection were compared using the Chi-square test. In contrast, quantitative variables were compared using the one-way analysis of variance (ANOVA) test or the Kruskal–Wallis ANOVA test. P < 0.05 was considered statistically significant. A receiver operating characteristic (ROC) curve was generated to find cut-offs for significant quantitative variables. The final analysis was performed after anonymizing potential identifiers from the study.


  Results Top


A total of 120 patients with spine infections were included in the study. Of these, 65 patients were diagnosed with probable TB and 55 were diagnosed as probable bacterial infections. Of the probable TB patients, four had isolated SI joint involvement, while 61 had vertebral involvement. Of these 61 patients, four patients had concomitant SI involvement. The mean number of vertebrae involvement in those with vertebral involvement was 2.6 ± 1.9. Of the 55 patients with bacterial infection, five had isolated SI joint involvement. Of the 50 patients with vertebral involvement, three had concomitant SI joint involvement. The mean number of vertebrae involvement was 2.8 ± 1.8.

Of the 120 patients, a total of 85 patients were confirmed with the microbiological diagnosis of interest [Table 1]. Concurrent pulmonary TB was present in nine patients with TB spine. Concurrent bacterial infection was present in six patients diagnosed with pyogenic spondylitis. Of the 23 patients with confirmed brucellosis, 16 had culture positivity of blood or pus or both. A total of 7 patients were diagnosed based on a four-fold rise or fall in titer. Of the 65 patients in whom SAT was done, 21 were positive. The sensitivity and specificity were calculated as 100%. None of the confirmed TB or pyogenic patients has a positive serology. The hallmark histopathological features of the three groups are depicted in [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g.
Table 1: Microbiological diagnosis of infectious causes of spine involvement

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Figure 1: Histopathological examination of vertebral bone/soft tissue in the hematoxylin-eosin stain at ×100 showing (a): Noncaseating necrosis with necroinflammatory debris (arrow) in a patient of pyogenic spondylitis; (b): Neutrophil rich acute inflammatory infiltrate (arrow) in a patient of pyogenic spondylitis; (c): Neutrophil rich infiltrate (arrowhead) with admixed cyst macrophages (arrow) in a patient of brucellosis; (d): Well-circumscribed non-caseating granuloma with Langhans type giant cells in a patient of brucellosis; (e): Epithelioid cell granuloma (arrow) with central caseation in a patient of pott's spine; (f) Caseous necrosis (arrow) in a patient of pott's spine; (g): Epithelioid cell granulomas with Langhans type giant cell (arrow) in a patient of pott's spine

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Involvement of the thoracic spine and longer duration of illness was more common in TB patients [Table 2]. On ROC curve analysis to differentiate TB versus other causes, duration of illness of 75 or more days had a sensitivity and specificity of 65.9% and 63.4%, respectively, with an area under the curve (AUC) of 0.72. On histopathological examination (HPE), necrosis, granuloma, and giant cells were more common in TB patients [Figure 1]e, [Figure 1]f, [Figure 1]g and [Table 3]. Male gender, involvement of lumbar vertebra, and neutrophilic infiltrate on HPE were more common in brucellosis patients [Figure c] and [Figure d] and [Table 2] and [Table 3]. Male gender, diabetes mellitus (DM), involvement of lumbar vertebra, neutrophilic infiltrate on HPE, leukocytosis, increased CRP, and longer duration of admission were more commonly seen in patients with pyogenic infection [Figure 1]a and [Figure 1]b and [Table 2] and [Table 3]. On ROC curve analysis, a CRP of 47.6 mg/dl or more had a sensitivity and specificity of 75% and 69.2%, respectively, in differentiating pyogenic from others (AUC-0.776). A ROC was generated for thin-layer chromatography to differentiate pyogenic versus others; a value of 8750/mm3 had a sensitivity and specificity of 66.7% and 64.6%, respectively (AUC-0.774).
Table 2: Clinical, radiological, and biochemical parameters of patients with infectious spondylitis and/or sacroiliitis

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Table 3: Histopathological parameters of patients with infectious spondylitis and/or sacroiliitis

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Based on the results of univariate analysis and ROC analysis, a scoring system was created to differentiate confirmed tubercular versus pyogenic spine involvement [Figure 2]. At a score of 5 or above with an AUC of 0.93 (95% confidence interval - 0.86–1, P < 0.001), the sensitivity and specificity of diagnosing a confirmed pyogenic infection were 75% and 91%, respectively [Figure 3].
Figure 2: Approach to the diagnosis of patients with infectious spondylodiscitis in resource-limited tropical settings

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Figure 3: Receiver operator characteristic curve to calculate the cut-off score that differentiates between pyogenic and tubercular spondylitis

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All except one patient were alive at the last follow-up [Table 4]. Of the 15 patients who were lost to follow-up, four patients left against medical advice at the first admission itself and did not follow-up. Of the remaining 11 patients, seven were showing some improvement in clinical and laboratory parameters, while the remaining four were not showing significant improvement at the last follow-up.
Table 4: Treatment and outcome of patients with infective spondylitis

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  Discussion Top


Although TB is the most common cause of spine involvement in tropical settings, this study showed that nontubercular causes as brucellosis, Staphylococcus spp. and E. coli are important as well. It is important to make a microbiological diagnosis in patients with vertebral osteomyelitis as the treatment options, duration, and course of treatment vary substantially according to the causative agent. Empirical therapy with ATT for other causes may be associated with catastrophic outcomes. Since it is often challenging to obtain invasive tissue samples for microbiological diagnosis in resource-limited settings, we suggest clinical pointers in the form of a scoring system that can be used for a more accurate empirical therapy.

TB Spine is the most common type of skeletal TB in the published literature.[6] The vertebra may get seeded with TB bacilli during the primary infection.[6] Therefore, past or concurrent TB infection at other sites, especially pulmonary, has been recorded. In our series, concurrent pulmonary TB was seen in 20.5% of the cases. In a study by Ali Chaudhry and Al-Solaiman of the 1388 patients with pulmonary TB, 1.5% had concomitant extrapulmonary multifocal involvement (primarily osteosteoarticular).[7] The foci in vertebrae are usually contained in immunocompetent but may reactivate as the age increases or in the setting of immunosuppression (e.g., HIV, chronic kidney disease). The period between primary infection and reactivation may be lesser in endemic countries, with several reports describing spinal TB in young individuals.[8] The lower thoracic and upper lumbar vertebrae are more commonly involved.[4] The infection begins anteriorly, and once the two adjacent vertebrae are involved, the intervening disc becomes involved. Disc involvement occurs late in TB when compared to pyogenic infection, and this may give an appearance of disc-sparing.[6] Due to disc involvement, vertebral collapse occurs, which leads to spine deformity and compression of the spinal cord.[6] The deformity is more common in TB compared to other causes.[4] Spinal cord compression also occurs due to the formation of epidural abscess. Compression on the spinal cord leads to paraparesis in a few cases. Neurological deficits range from 23% to 76% in the published literature.[4],[6] Constitutional symptoms such as fever and weight loss are less common when compared to pulmonary TB.[4] In our study, fever and weight loss were seen in 45% and 18% of the cases, respectively. On HPE, caseating necrosis, Langhans giant cell, and epithelioid granuloma have been described.[3] These three features were significantly helpful in differentiating TB from nontubercular causes (1E-G). Although necrosis was seen in patients with pyogenic osteomyelitis and granulomas in two patients with brucellosis, caseation was not seen in non-TB cases [Figure 1]. The presence of acid-fast bacilli in tissue specimens, although diagnostic, is seen only in a small fraction of cases.[6] Furthermore, the pathologist report of suspected TB had more concurrence with confirmed TB diagnosis when compared to the radiology report. This suggests the possible need for increased tissue biopsies for the diagnosis of spine infections. Molecular methods such as GeneXpert have excellent sensitivity and specificity and perform as well or even better than the traditional reference standard method of cultures.[6] In limited-resource settings where the microbiological diagnosis of TB is difficult to establish, empirical ATT may be started. ATT of 12–18 months of duration is the treatment of choice for spinal TB. In our study, the mean duration of treatment was 16.4 months.

Brucella is transmitted most commonly by the consumption of an animal product. Local tissue lymphocytes take up the bacteria, and from the regional lymph nodes, they enter the circulation and can seed to various sites, including vertebrae.[9] Generally, patients present with fever, night sweats, and arthralgia. Bone involvement is the most common focal complication of brucellosis and is seen in up to 85% of the cases.[9] The spine (2%–54%) and/or sacroiliac joint (up to 85%) are most commonly involved.[9] In four series of brucellosis, the frequency of spondylodiscitis ranged from 9.7% to 21.2%.[10] Similar to our series, spine involvement is more common in older patients, and the presentation is subacute to chronic.[9] Like our findings, the male gender has some predilection to brucellosis.[9],[10] Lumbar vertebrae are the most commonly involved vertebrae.[10] On HPE, noncaseating granuloma along with lymphocytic infiltration has been described.[3] In our study, most patients had a mixed neutrophil, and lymphocytic infiltrate [Figure 1]c. A noncaseating granuloma was only seen in two patients [Figure 1]d. SAT is rarely negative in patients with Brucella spondylodiscitis.[3] Our study showed excellent sensitivity and specificity of SAT, indicating its usefulness in the diagnosis of brucellosis. In a study of patients with brucella spondylodiscitis, 41% had positive blood culture.[10] In our study, 43% of the patients had positive blood culture while 38% had positive pus culture. It is recommended that in endemic areas, blood cultures should be incubated for 2 weeks or more.[3] However, in routine practice, most blood cultures for Brucella spp. are positive by 5 days. The treatment of brucellosis consists of aminoglycoside for the first 2 weeks along with doxycycline and rifampicin for a total of 12 weeks. All patients in our cohort showed significant responses to the treatment regimen.

Pyogenic spondylitis most commonly results from hematogenous seeding of vertebral bodies from a distant focus and involves the adjacent intervertebral disc. It can also occur from direct inoculation (trauma or surgery) or contiguous spread from adjoining soft tissue infection (aorta, esophagus, bowel). Similar to our series, it occurs more commonly in adults with an average age of around 50 years, and men may have a slight predilection.[4],[11] The vertebra receives blood supply via nutrient vessels of the posterior spinal artery. As age increases, the anatomy of the vessels gets distorted in a way that predisposes the vertebra to be seeded.[11] The median age in patients with pyogenic spondylodiscitis was found to be 67 years in a large study.[11] According to an estimate, the incidence of pyogenic osteomyelitis in patients with <20 years of age is 0.3/100 thousand, whereas the number rises to 6.5/100 thousand in those with more than 70 years of age.[5] Common risk factors of pyogenic spondylitis include prior history of degenerative spine disease, infection at other sites (endocarditis, genitourinary infection, etc.), DM, and immunosuppression.[12] DM was significantly more common in those with pyogenic spondylodiscitis in this study. Similar to our series, the lumbar vertebrae are most involved, followed by the thoracic vertebrae in the published literature.[4],[13] The extension of infection posteriorly can lead to an epidural abscess, while lateral extension leads to a paravertebral abscess. Most patients have a monomicrobial infection. Similar to our cohort, the most common cause of vertebral osteomyelitis is Staphylococcus aureus, accounting for more than 50 per cent of cases in most series from developed countries.[3],[4],[5],[13] Enteric gram-negative bacilli such as E. coli and Streptococcus spp can also cause pyogenic osteomyelitis.[3],[4] Like TB, the presentation is insidious and progresses slowly; however, acute presentation is also frequently described. Fever is not common and is seen in about 10%–45% of the patients.[4] In our series, fever was present in only 22% of the patients. In a systematic review of 1008 patients, neurological deficits were seen in 32% of the patients.[12] The X-ray may take 3–6 weeks to show significant bone destruction. Therefore, MRI is the imaging of choice with an accuracy of 94%.[3] Previous studies have shown that increased CRP has a high sensitivity for diagnosing pyogenic osteomyelitis.[5] However, leukocytosis was not found to be useful.[5] In this study, both CRP and leukocyte count were found to be useful in differentiating pyogenic from others. Blood culture can be positive in up to 78% of cases.[5] Although biopsy has a higher yield (up to 100%) than blood culture, blood culture positivity negates the need for biopsy and may serve to be very useful in resource-limited settings.[3],[5] Those patients with suspected pyogenic osteomyelitis should be started on empiric therapy if the patients have a neurological disability or hemodynamic instability at presentation.[3] Those patients who are stable at presentation should be treated with targeted therapy based on susceptibility results.[3] In a noninferiority trial for the treatment of pyogenic spondylodiscitis, a 6-week duration of therapy was noninferior to 12 weeks.[14] Classically IV therapy was used for the management, but recent studies have shown that de-escalation to oral therapy after 2 weeks of IV therapy may be an acceptable option.[15] The patients should be followed-up clinically and biochemically for improvement. Most patients show a significant decline in CRP in the first 2 weeks.[3]

In this study, we compared clinical, laboratory, and radiological manifestations of confirmed TB, brucellosis, and pyogenic infection of the spine. Since invasive procedures may not be available in resource-limited settings, the study attempted to find clinically relevant information obtained from noninvasive tests that can be used in differentiating these similar illnesses. We did not include radiological findings in the scoring system as the radiology report of possible TB did not correlate significantly with the final microbiological diagnosis of TB. Other than the predominance of the thoracic vertebra involvement in those with TB and lumbar involvement in those with brucellosis and pyogenic infection, there were no significant differences in terms of the number of vertebrae involved and the adjacent soft tissue/muscle involvement. Previous studies have shown that TB can have several radiological mimics.[16] In [Figure 2], we have summarized a potential approach that can be taken while deciding empiric therapy in patients with spine infections. Brucella SAT has shown to have high sensitivity and specificity for diagnosing osteoarticular brucellosis.[3] It can be done in resource-limited areas as the first test to differentiate Brucella spp. as a cause of infection from others. Those patients who are negative by serology can then be diagnosed as confirmed pyogenic infection if their blood culture is positive for typical organisms. Those negative for blood culture can be differentiated by the scoring system developed in this article into probable pyogenic and probable tubercular spondylitis. These patients should be confirmed by biopsy whenever possible. If a biopsy is not possible, probable pyogenic infections should be treated with empiric antimicrobial therapy. It should be noted that in patients where TB has not been ruled out, fluoroquinolones should be avoided as empiric therapy in TB-endemic areas.[17] If there is a significant decrease in CRP levels after 2 weeks, they can be continued on antimicrobial therapy for 6 weeks.[3] In the absence of significant clinical or biochemical response, they can be treated with empiric ATT just like the patients diagnosed with probable TB.


  Conclusions Top


Brucellosis and other bacterial infections are as important a cause of infectious spine involvement as TB. Therefore, it is essential to diagnose the etiological cause for the initiation of appropriate therapy. In resource-limited settings, suggestive clinical and laboratory findings can be used to decide empiric treatment.

Limitations of the study

This was a retrospective study and therefore was associated with inherent biases. Findings such as fever and weight loss may have been under-reported. Also, because this was a tertiary care center receiving referrals from nearby districts, the follow-up of many patients was not available to determine the outcomes. The relatively higher number of losses to follow-ups may be because of lack of treatment response or that the patient preferred to consult with a local doctor after the initial diagnosis. The use of clinical improvement in outcomes did not have any specific definitions and was dependent on the clinical assessment of the treating physicians.

Ethical clearance

IEC number 470/2020, Date: October 20, 2021.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Buranapanitkit B, Lim A, Geater A. Misdiagnosis in vertebral osteomyelitis: Problems and factors. J Med Assoc Thai 2001;84:1743-50.  Back to cited text no. 2
    
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Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015;61:e26-46.  Back to cited text no. 3
    
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Gasbarrini AL, Bertoldi E, Mazzetti M, Fini L, Terzi S, Gonella F, et al. Clinical features, diagnostic and therapeutic approaches to haematogenous vertebral osteomyelitis. Eur Rev Med Pharmacol Sci 2005;9:53-66.  Back to cited text no. 4
    
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Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med 2010;362:1022-9.  Back to cited text no. 5
    
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Dunn RN, Ben Husien M. Spinal tuberculosis: Review of current management. Bone Joint J 2018;100-B: 425-31.  Back to cited text no. 6
    
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Ali Chaudhry L, Al-Solaiman S. Multifocal tuberculosis: Many faces of an old menace. Int J Mycobacteriol 2013;2:58-69.  Back to cited text no. 7
    
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Chaudhry LA, Zamzami M, Fakharudin SK. Paraplegia is not a diagnosis: Spinal tuberculosis deserves a place on the clinical radar screen: Awakening call to clinicians. Int J Mycobacteriol 2012;1:155-60.  Back to cited text no. 8
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Esmaeilnejad-Ganji SM, Esmaeilnejad-Ganji SMR. Osteoarticular manifestations of human brucellosis: A review. World J Orthop 2019;10:54-62.  Back to cited text no. 9
    
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Bozgeyik Z, Ozdemir H, Demirdag K, Ozden M, Sonmezgoz F, Ozgocmen S. Clinical and MRI findings of brucellar spondylodiscitis. Eur J Radiol 2008;67:153-8.  Back to cited text no. 10
    
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Gupta A, Kowalski TJ, Osmon DR, Enzler M, Steckelberg JM, Huddleston PM, et al. Long-term outcome of pyogenic vertebral osteomyelitis: A cohort study of 260 patients. Open Forum Infect Dis 2014;1:ofu107.  Back to cited text no. 11
    
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Mylona E, Samarkos M, Kakalou E, Fanourgiakis P, Skoutelis A. Pyogenic vertebral osteomyelitis: A systematic review of clinical characteristics. Semin Arthritis Rheum 2009;39:10-7.  Back to cited text no. 12
    
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McHenry MC, Easley KA, Locker GA. Vertebral osteomyelitis: Long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis 2002;34:1342-50.  Back to cited text no. 13
    
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Bernard L, Dinh A, Ghout I, Simo D, Zeller V, Issartel B, et al. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: An open-label, non-inferiority, randomised, controlled trial. Lancet 2015;385:875-82.  Back to cited text no. 14
    
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Babouee Flury B, Elzi L, Kolbe M, Frei R, Weisser M, Schären S, et al. Is switching to an oral antibiotic regimen safe after 2 weeks of intravenous treatment for primary bacterial vertebral osteomyelitis? BMC Infect Dis 2014;14:226.  Back to cited text no. 15
    
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Chaubey J, Shrivastava D, Pawar S, Singh BK, Sharma R, Sinha S. High degree of fluoroquinolone resistance among extrapulmonary tuberculosis patients at a tertiary care center in North India. Int J Mycobacteriol 2020;9:309-12.  Back to cited text no. 17
[PUBMED]  [Full text]  


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