<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="other" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.74393.2</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Clinical Practice Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>The cocktail infection: anaerobic and aerobic co-Infections in tubercular vertebral osteomyelitis</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 2; peer review: 1 approved with reservations, 2 not approved]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Bhat</surname>
                        <given-names>Shyamasunder N</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-9545-4838</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Kundangar</surname>
                        <given-names>Raghuraj</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Ampar</surname>
                        <given-names>Nishanth</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-4696-7167</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sait</surname>
                        <given-names>Anika</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-0159-0105</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Shenoy</surname>
                        <given-names>Padmaja Ananth</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Sukumar</surname>
                        <given-names>Cynthia Amrutha</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-7026-2474</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Saravu</surname>
                        <given-names>Kavitha</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-6399-1129</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Kasturba Medical College, Manipal University, Manipal, India</aff>
                <aff id="a2">
                    <label>2</label>Manipal Centre for Infectious Diseases (MAC ID), PSPH, Manipal Academy of Higher Education, Manipal, India</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:cynthiaamrutha@gmail.com">cynthiaamrutha@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>9</day>
                <month>12</month>
                <year>2022</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2022</year>
            </pub-date>
            <volume>11</volume>
            <elocation-id>130</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>5</day>
                    <month>12</month>
                    <year>2022</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2022 Bhat SN et al.</copyright-statement>
                <copyright-year>2022</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/11-130/pdf"/>
            <abstract>
                <p>
                    <bold>Background:</bold> Anaerobic organisms have been known to have an association with dental infections, bacteremia, endocarditis and soft tissue infections. However, anaerobic isolation from bone and joint infections are relatively rare. Sparse literature has been found on reports of anaerobic osteomyelitis. There is no literature reported on anaerobic osteomyelitis complicating Tuberculosis of spine.</p>
                <p>
                    <bold>Case Report:</bold> We report two cases of tuberculosis of spine complicated by aerobic and anerobic infections. The first is a case of a young female who presented with chronic lower backache and fever. Examination revealed a lumbar scoliosis with paraspinal tenderness. Magnetic resonance imaging (MRI) of the spine showed lumbar spondylodiscitis with multiple abscesses. There were air-fluid levels noted in the abscesses. The pus sent for CBNAAT (cartridge based nucleic acid amplification test) was positive. Further the cultures also grew 
                    <italic toggle="yes">Escherichia coli</italic> (aerobic) 
                    <italic toggle="yes">Bacteroids fragilis</italic> and 
                    <italic toggle="yes">Peptoniphilus asachrolyticus</italic> (anaerobic) organisms. She improved with a course of intravenous antibiotics and decompression surgery.</p>
                <p>The second case is a middle aged man who presented with chronic neck pain and fever. Examination revealed kyphosis of the neck with spasm of the neck muscles and midline tenderness. MRI showed C4-5 cervical spondylodiscitis with parapharyngeal collections showing air-fluid levels. The pus culture showed 
                    <italic toggle="yes">Streptococcus constellatus (aerobic)</italic> and 
                    <italic toggle="yes">Prevotella</italic> sps. (anaerobic). The CBNAAT report was positive for 
                    <italic toggle="yes">Mycobacterium tuberculosis.</italic> The patient was treated with intravenous antibiotics and cervical decompression.</p>
                <p>
                    <bold>Conclusion:</bold> Though tubercular vertebral osteomyelitis (TVO) is usually a diagnosis in itself, it should not hinder us from considering secondary infections (both aerobic and anaerobic) complicating the osteomyelitis. Further, the presence of air-fluid levels on imaging studies and the presence of foul smell during operative exploration of the spine must arouse the suspicion of an anaerobic co-infection. Isolation and treatment of these organisms are crucial as they may hamper the clinical outcome of the primary TVO.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Anaerobic osteomyelitis</kwd>
                <kwd>Prevotella</kwd>
                <kwd>Bacteroides</kwd>
                <kwd>Peptostreptococcus</kwd>
                <kwd>spondylodiscitis</kwd>
                <kwd>tuberculosis of Spine</kwd>
                <kwd>Tubercular Vertebral Osteomyelitis</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
        <notes>
            <sec sec-type="version-changes">
                <label>Revised</label>
                <title>Amendments from Version 1</title>
                <p>The manuscript has been revised to include additional details of the patients&#x2019; physical examination, chest radiograph findings, MRI images, details of treatment given and outcome. In case 1, we have described that the patient was febrile on admission with paraspinal tenderness in the lumbo-sacral region. Chest Radiograph was done and found to be normal. Additional radiological images 1c and 1d have been included for case 1 to indicate spondylodiscitis. Figure 1c is an MRI (T2 flair) transverse section lumbar spine indicating Abscess with air-fluid level. Figure 1d is an MRI lumbar spine (Saggital section) indicating the right psoas abscess. Follow-up details and outcome also included. In case 2, we have confirmed that there were no co-morbidities or any relevant psych-social or genetic history obtained from the patient. We have also noted that the patient had an improvement in the anemia, ESR and weight gain on follow-up. Literature search to find similar cases with tubercular vertebral osteomyelitis and anaerobic infection was also done and details included in the manuscript. The strengths and limitations of this case have also been detailed after the discussion.</p>
            </sec>
        </notes>
    </front>
    <body>
        <sec id="sec1" sec-type="intro">
            <title>Introduction</title>
            <p>Anaerobic organisms have been known to have an association with dental infections, bacteremia, endocarditis and soft tissue infections.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> However, anaerobic isolation from bone and joint infections are relatively rare. This could be attributed to the fastidious nature of the organism which makes isolation from the bone and joint infections cumbersome.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup>
            </p>
            <p>The most common organisms implicated in anaerobic osteomyelitis are Bacteroides, Fusobacterium, Peptostreptococcus and Clostridium species. Predisposing factors include children, contiguous spread of infection, vascular disease and complicated fractures.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> Sparse literature has been found on reports of anaerobic osteomyelitis. There is no literature reported on anaerobic osteomyelitis complicating Tuberculosis of spine/Tubercular vertebral osteomyelitis (Pott&#x2019;s spine). However, our cases highlight the rare isolation of gram-negative anaerobes (
                <italic toggle="yes">Prevotella, Bacteroides, Peptoniphilus</italic>) from Tubercular vertebral osteomyelitis (TVO) in immunocompetent adults diagnosed with tuberculosis of spine.</p>
        </sec>
        <sec id="sec21">
            <title>Materials/Methods</title>
            <p>Two cases of infectious spondylodiscitis have been presented in this case series.</p>
            <p>
                <bold>
                    <italic toggle="yes">Consent</italic>
                </bold>
            </p>
            <p>Written informed consent for publication of their clinical details and/or clinical images was obtained from the patients.</p>
        </sec>
        <sec id="sec2">
            <title>Case report</title>
            <sec id="sec3">
                <title>Case 1</title>
                <p>A 22-year-old poorly built (body mass index: 16 kg/m
                    <sup>2</sup>) lady from rural South India who was pursuing her undergraduate degree, presented with complaints of low back ache of one-month duration. It was insidious in onset and gradually radiated to the right gluteal region. She was able to walk only a few steps with a limp. There was no bowel or bladder disturbance. She preferred to keep her right hip flexed to about 30 degrees in supine position. The backache was associated with high grade fever with chills and rigors. There was no history of tuberculosis in her family or her community. She had no significant history suggestive of immunosuppression. She had no known co-morbidities. There was no significant genetic history given by the patient.</p>
                <p>On examination, she was febrile (102&#x00b0; F) with a pulse rate of 98 beats/minute. There was midline and right paraspinal tenderness from L3 to sacral region. Neurological examination of lower limbs was unremarkable. There was no focal neurological deficit.</p>
                <p>Lab investigations showed that she was anaemic (Haemoglobin of 8 g/dl). Her total counts were 13600/mm
                    <sup>3</sup> (predominantly neutrophilia). The ESR was elevated (88 mm/hour) and CRP (261mg/L). The renal function tests were within normal limits, while serum albumin was only 1.9 mg/dl. Blood and urine cultures were sterile. Her chest x-ray showed no evidence of tuberculosis.</p>
                <p>A radiograph revealed mild lumbar scoliosis to the left side and bulky psoas muscle in the right side (
                    <xref ref-type="fig" rid="f1">Figure 1a</xref> and 
                    <xref ref-type="fig" rid="f1">b</xref>).</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>Figure 1. </label>
                    <caption>
                        <title>a: Radiograph of Spine (AP view). Arrow indicating bulky psoas muscle. b: Radiograph of Spine (lateral view). c: MRI (T2 flair) transverse section lumbar spine. Arrow indicating Abscess with air-fluid level. d: MRI lumbar spine. Saggital section. Arrow indicating right psoas abscess. e: MRI lumbar spine (T2/STIR) showing post-contrast enhancement in L5-S1 disc and adjacent end plates. f: Radiograph of spine (lateral) before and after treatment.</title>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/140334/9cee4fd4-4d52-452e-b109-bbf57b3d6a87_figure1.gif"/>
                </fig>
                <p>MRI spine revealed features suggestive of spondylodiscitis of L5-S1, spondylitis of L4 with abscesses adjacent to L4, L5, S1, S2 and S3 vertebra in the right side. There was also air-fluid level in the abscess (
                    <xref ref-type="fig" rid="f1">Figure 1c</xref> and 
                    <xref ref-type="fig" rid="f1">d</xref>). The spondylodiscitis can be appreciated in the 
                    <xref ref-type="fig" rid="f1">Figure 1e</xref> which shows post-contrast enhancement in L5-S1 vertebral discs. 
                    <xref ref-type="fig" rid="f1">Figure 1f</xref> shows the radiographs before treatment and after treatment for comparison.</p>
                <p>In view of the psoas abscess and radiological evidence of spondylodiscitis, she underwent surgery involving decompression of L5 vertebra and exploration of L5-S1 space with drainage of the abscess. Intra-operatively foul-smelling gas escaped from the abscess. The L5-S1 disc also had purulent collection. Pus was sent for CBNAAT (cartridge based nucleic acid amplification test) for tuberculosis, aerobic and anaerobic cultures. Material from L5-S1 disc was sent for histopathology.</p>
                <p>On the third hospital day CBNAAT report was suggestive of 
                    <italic toggle="yes">Mycobacterium tuberculosis</italic> she was started on anti-tubercular therapy (ATT). The next day the aerobic culture grew 
                    <italic toggle="yes">Escherichia coli</italic> whereas anaerobic culture grew 
                    <italic toggle="yes">Bacteroids fragilis</italic> and 
                    <italic toggle="yes">Peptoniphilus asachrolyticus.</italic> In addition, she was also started on injection Piperazillin-Tazobactem and oral tinidazole for 10 days. There was wound dehiscence on tenth postoperative day.</p>
                <p>The repeat culture from the pus drained grew only 
                    <italic toggle="yes">E. coli</italic> with similar sensitivity though the growth was scanty. We continued antitubercular drugs and added Injection Amikacin and Imipenem (as per the culture sensitivity report) for a total of three weeks. She was taken up for secondary suturing during this period. Patient was discharged subsequently. On follow-up at one month, her symptoms had improved and her anemia had improved to 9.5 gm%. She had also gained 1.6 kgs in weight. Repeat radiographs and MRI were done at the three-month follow-up and showed resolution of the abscesses. Patient was adherent and tolerated the anti-tubercular medications well. She was continued on ATT for 18 months. She did not have any ATT related complications and was compliant with the treatment throughout the follow-up.</p>
            </sec>
            <sec id="sec4">
                <title>Case 2</title>
                <p>A 54-year-old man from an urban district of South India, a tailor by occupation, came with complaints of insidious onset of neck pain of about three weeks duration. The pain was gradually progressive over the past 10 days. The pain would aggravate on movements of the neck, but there was no radiculopathy. There was also associated fever with chills and rigors. He reported significant weight loss in the recent past. There was no history of medical co-morbidites. There was no relevant psycho-social or genetic history obtained from the patient.</p>
                <p>On examination, neck appeared short and kyphotic. There was midline tenderness from C4-C7 region. Movements of the neck was grossly restricted due to pain and spasm. He was unable to flex his neck without significant pain. The elbow flexion was MRC Grade 4/5 on both sides. There was no sensory deficits and reflexes were normal. He was anaemic (Hb 10 g/dl) with neutrophilia. ESR was moderately elevated at 68 mm/hour. His chest radiograph was normal.</p>
                <p>In an X-ray of the cervical spine, we noted increased prevertebral soft tissue shadow and erosion of vertebral end plates at C4-5 level with gross kyphosis. Air-fluid levels were also seen in the prevertebral soft tissue shadow (
                    <xref ref-type="fig" rid="f2">Figure 2a</xref> and 
                    <xref ref-type="fig" rid="f2">b</xref>).</p>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>Figure 2. </label>
                    <caption>
                        <title>a: Radiograph cervical spine (lateral). b: Radiograph cervical spine (AP view). Arrow indicationg soft tissue shadow with air-fluid levels. c: MRI cervical spine (saggital view). d: MRI cervical spine (transverse view). Arrows indicating parapharyngeal collection with C4-5 spondylodiscitis. e: Cervical spine AP view. Post-operative radiographs. f: Cervial Spine lateral view. Post-operative radiographs.</title>
                    </caption>
                    <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/140334/9cee4fd4-4d52-452e-b109-bbf57b3d6a87_figure2.gif"/>
                </fig>
                <p>MRI of the cervical spine confirmed spondylodiscitis of C4-C5 with cord compression. Multiple collections in parapharyngeal space communicating with the pre-vertebral space were also seen along with air-fluid levels (
                    <xref ref-type="fig" rid="f2">Figure 2c</xref> and 
                    <xref ref-type="fig" rid="f2">d</xref>)</p>
                <p>By this time the blood culture grew 
                    <italic toggle="yes">Streptococcus constellatus</italic> and he was started on Injection ceftriaxone (2gm q24h) as per sensitivity report. His urine culture was sterile and Brucella agglutination test was negative.</p>
                <p>He underwent anterior cervical decompression, by C5 corpectomy and fusion (
                    <xref ref-type="fig" rid="f2">Figure 2e</xref> and 
                    <xref ref-type="fig" rid="f2">f</xref>). A distinct foul-smelling odour was noted intra-operatively and around 100 ml of pus was drained. The C4 and C5 vertebrae were completely destroyed with surrounding caseous material. Pus was sent for aerobic and anaerobic cultures and the caseating tissue was sent for histopathology. Patient tolerated the procedure well.</p>
                <p>The aerobic bacterial culture from the pus grew 
                    <italic toggle="yes">Streptococcus constellatus</italic> with similar sensitivity as that of his blood culture. Anaerobic culture grew 
                    <italic toggle="yes">Prevotella</italic> sps. The CBNAAT report was positive for 
                    <italic toggle="yes">Mycobacterium tuberculosis.</italic> Histopathology confirmed granulation tissue with epitheloid cells and Langhans giant cells suggestive of tubercular osteomyelitis.</p>
                <p>He was started on Antitubercular therapy and Injection Metronidazole (500 mg q8h for two weeks) in addition to Injection Ceftriaxone (two weeks). The wound healed well. Anti-tubercular treatment was initiated and the patient was followed up on OPD basis. He was compliant with treatment and took the ATT for a total of 15 months. Improvement in anemia and ESR, weight gain as well as radiological improvement was noted in this patient on follow-up.</p>
            </sec>
        </sec>
        <sec id="sec5" sec-type="discussion">
            <title>Discussion</title>
            <p>Anaerobic osteomyelitis was first reported in 1884 by Von Langenbeck in case of vertebral osteomyelitis.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> Decades later, Taylor and Davies noted the presence of anaerobic organisms within sequestra in 55% of patients with chronic osteomyelitis.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> It was found that these anaerobic organisms were more frequently isolated from the inside of the sequestra and were usually mixed isolates i.e two or more anaerobic isolates were isolated. The chronicity of the osteomyelitis was directly proportional to the frequency of anerobic isolates found.</p>
            <p>In a retrospective study done on osteomyelitis by Lewis 
                <italic toggle="yes">et al</italic>., it was found that 39 percent of patients with osteomyelitis had anaerobic infections.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> This serves to prove that anaerobes play a much larger role in osteomyelitis than known previously. It is likely that these infections are less reported due to poor awareness of their prevalence and the cumbersome methods of isolation.</p>
            <p>However, these organisms were found as a part of the mixed flora which included gram positive cocci, gram negative bacilli and other anaerobes. This is consistent with the pattern of mixed infections reported in our case report. Our first patient was found to have anaerobic 
                <italic toggle="yes">Prevotella</italic> infection from epidural abscess with associated Streptococcus bacteremia in a chronic tubercular vertebral osteomyelitis. Our second case was also found to have a combination of anaerobes comprising of 
                <italic toggle="yes">Bacteroides, Peptoniphilus (Peptotreptococcus)</italic> and 
                <italic toggle="yes">Clostridium</italic> with gram-negative 
                <italic toggle="yes">Pseudomonas aeruginosa</italic> isolated from a psoas abscess secondary to a chronic tubercular vertebral osteomyelitis.</p>
            <p>The predisposing factors contributing to anaerobic osteomyelitis usually include children, diabetes mellitus, oral infections or procedures, upper respiratory tract infections, trauma, peripheral neuropathy and complicated fractures.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> It is interesting to note that both our patients had no pre morbidities to predispose them to anaerobic osteomyelitis.</p>
            <p>In a review by Raff and Melo of a large series of 193 anaerobic osteomyeltits cases collected from the world literature published between 1936 to 1976, it was the found that the most common anaerobe implicated in osteomyelitis was 
                <italic toggle="yes">Bacteroides</italic> followed by 
                <italic toggle="yes">Peptostreptococcus</italic> and 
                <italic toggle="yes">Fusobacterium</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> This trend was confirmed by a study by Ziment 
                <italic toggle="yes">et al.</italic> who found the most common isolate being 
                <italic toggle="yes">Bacteroides</italic> followed by 
                <italic toggle="yes">Peptostreptococcus</italic> and 
                <italic toggle="yes">Fusobacterium</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> This similar trend of occurrence was noted in a large study done on 134 cases of pyogenic osteomyelitis by Haider 
                <italic toggle="yes">et al</italic>. between 1992 to 1993.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup> This trend agrees with our case of anaerobic osteomyelitis which showed a mixed anaerobic isolate of 
                <italic toggle="yes">Bacteroides</italic> with 
                <italic toggle="yes">Peptostreptococcus</italic> and 
                <italic toggle="yes">Clostridium.</italic>
            </p>
            <p>A review of literature on available data on anaerobic osteomyelitis with 
                <italic toggle="yes">Prevotella</italic> isolates shows only nine cases reported till date.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
                <sup>&#x2013;</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup> Among this only one case reports secondary 
                <italic toggle="yes">Prevotella</italic> infection on chronic tubercular vertebral osteomyelitis. A summary of the data available on Anaerobic osteomyelitis with 
                <italic toggle="yes">prevotella</italic> isolates are shown in 
                <xref ref-type="table" rid="T1">Table 1</xref>.</p>
            <table-wrap id="T1" orientation="portrait" position="float">
                <label>Table 1. </label>
                <caption>
                    <title>Clinical characteristics of patients with 
                        <italic toggle="yes">Prevotella</italic> isolated from vertebral osteomyelitis (previous data).</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="1" rowspan="1" valign="top">Authors</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Age/sex</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Level of osteomyelitis</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Organism isolated</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Risk factors</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Clinical outcome</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Surbled et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref8">8</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">44/M</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">L5-S1</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. melanogenica</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">none</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Salavert et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref9">9</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">27/F</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">L2-L3</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. melanogenica</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">IV drug use</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Fukuoka et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref10">10</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">60/M</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">T7-T8</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. intermedia</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Age</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Sch&#x00f6;ber et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref11">11</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">45/F</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">L1-L2</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. intermedia</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">None</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Mukhyopadhyay et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref12">12</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">35/F</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">S1</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. melanogenica</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Dental cleaning</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Salliot et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref13">13</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">62/M</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">L5-S1</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">Prevotella</italic> spp.
                                <xref ref-type="table-fn" rid="tfn1">
                                    <italic toggle="yes">*</italic>
                                </xref>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Age, steroids</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Purushothaman et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref14">14</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">74/F</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">L3-L4</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">Prevotella</italic> spp.
                                <xref ref-type="table-fn" rid="tfn1">
                                    <italic toggle="yes">*</italic>
                                </xref>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Age, ovarian malignancy</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Huang et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref15">15</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">73/F</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">T12-L3</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. melanogenica</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Age, diabetes</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Patient died</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Goyal et al
                                <sup>
                                    <xref ref-type="bibr" rid="ref16">16</xref>
                                </sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">68/F</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">T6-T8</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <italic toggle="yes">P. oralis</italic>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Age, gastrointestinal procedure</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Favourable</td>
                        </tr>
                    </tbody>
                </table>
                <table-wrap-foot>
                    <fn-group content-type="footnotes">
                        <fn id="tfn1">
                            <label>*</label>
                            <p>Species could not be identified.</p>
                        </fn>
                    </fn-group>
                </table-wrap-foot>
            </table-wrap>
            <p>A literature search was done to identify other published reports of anaerobic infections complicating tubercular vertebral osteomyelitis. However, we found only one case report by Salavert M et al who reported a combination of Prevotella and Candida infection in an intravenous drug abuser diagnosed with tubercular vertebral osteomyelitis in 1997.
                <sup>
                    <xref ref-type="bibr" rid="ref17">17</xref>
                </sup>
            </p>
            <p>Both our cases did not show any evidence of hematogenous osteomyelitis. This finding concurs with evidence found by in a review study on 61 cases of anaerobic osteomyelitis of long bones
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> where 29.5% of the cases were hematogenous and 32.8% were exogenous osteomyelitis. The study by Lewis 
                <italic toggle="yes">et al.</italic> also shows a preponderance towards exogenous osteomyelitis.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> In both our cases we could not ascertain how these polyorganisms could infect the spine.</p>
            <p>Management of anaerobic osteomyelitis includes a two-pronged approach with adequate drainage of purulent material and parenteral administration of antibiotics for at least four to eight weeks.
                <sup>
                    <xref ref-type="bibr" rid="ref19">19</xref>
                </sup> The antibiotics were decided according to the sensitivity pattern noted on culture.&#x00a0;</p>
            <p>Strengths and limitations: The strength of this case series is the similar clinical presentation of both the cases and the presence of aerobic and anaerobic infections in both of them. However, we were unable to follow up the second case beyond two months as he opted for care under a local orthopaedician due to travel constraints. This was one of the limitations of our case series. As a result of this adherence and tolerance of the treatment could not be assessed in the second case.</p>
        </sec>
        <sec id="sec6" sec-type="conclusion">
            <title>Conclusion</title>
            <p>Though tubercular vertebral osteomyelitis is usually a diagnosis in itself, it should not hinder us from considering secondary infections (both aerobic and anaerobic) complicating the osteomyelitis. Further, the presence of air-fluid levels on imaging studies and the presence of foul smell during operative exploration of the spine must arouse the suspicion of an anaerobic co-infection. Isolation and treatment of these organisms are crucial as they may hamper the clinical outcome of the primary TVO. Therefore, the cocktail of organisms, both aerobic and anaerobic isolated in these cases highlights the importance of suspecting, isolating and treating these lurking organisms in cases of tuberculosis of spine.</p>
            <sec id="sec7">
                <title>Patient perspective</title>
                <p>
                    <list list-type="order">
                        <list-item>
                            <label>1.</label>
                            <p>I was suffering from severe back ache for over 2 years with recurrent fever. I was unable to continue my studies also as sitting in class was very painful. I received treatment at several local hospitals but the fever persisted and the pain was not alleviated. Following admission at Kasturba hospital, Manipal, I underwent an MRI of my spine and the doctors found the source of infection in my spine. I underwent a decompression surgery with treatment with TB medicines and intravenous medications at the hospital. The fever subsided in the first week following treatment. Gradually I was able to move around with support and at my 3 month follow-up, I walked without pain to the hospital. I am much better now and have rejoined college to continue my studies.</p>
                        </list-item>
                        <list-item>
                            <label>2.</label>
                            <p>I had neck stiffness and pain for many years. The pain radiated to my arms and I struggled to sit and work for long hours with my neck bent forward. In the hospital, a team of doctors examined me and suspected a spine infection. An MRI confirmed infection of the neck bones and pus collections. I underwent a surgery on my neck and received a long course of medicines in the hospital and at home. I noted a significant improvement in my pain and fever. I was symptom free by my 2-month follow-up at the hospital.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
        </sec>
    </body>
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    </back>
    <sub-article article-type="reviewer-report" id="report182021">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.140334.r182021</article-id>
            <title-group>
                <article-title>Reviewer response for version 2</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Xu</surname>
                        <given-names>Yongqing</given-names>
                    </name>
                    <xref ref-type="aff" rid="r182021a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r182021a1">
                    <label>1</label>Hospital of the Joint Logistics Support Force of the PLA, Kunming, China</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>11</day>
                <month>7</month>
                <year>2023</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2023 Xu Y</copyright-statement>
                <copyright-year>2023</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport182021" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.74393.2"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>reject</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>The ideas put forward in this paper have research value, and the mixed infection of anaerobic bacteria combined with spinal tuberculosis can provide new ideas in clinical treatment, but there are the following problems: 
                <list list-type="order">
                    <list-item>
                        <p>First of all, there have been reports about anaerobic osteomyelitis. Originally, tuberculosis bacillus may cause erosion and destruction of bone and soft tissue, and then colonizing bacteria migration of tissues and organs around the lesion, resulting in mixed infection;</p>
                    </list-item>
                    <list-item>
                        <p>This paper mainly reports 2 cases of mixed bacterial infection of tuberculosis bacilli. What is the main purpose of this paper? Lack of innovation in treatment options</p>
                    </list-item>
                    <list-item>
                        <p>Is it necessary to study the sequence of tuberculosis and mixed bacterial infections in order to facilitate clinical preventive treatment? This will make the paper more valuable</p>
                    </list-item>
                </list>
            </p>
            <p>Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?</p>
            <p>Yes</p>
            <p>Is the background of the cases&#x2019; history and progression described in sufficient detail?</p>
            <p>No</p>
            <p>Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?</p>
            <p>Partly</p>
            <p>Is the conclusion balanced and justified on the basis of the findings?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Osteomyelitis，microsurgery</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment15579-182021">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Sukumar</surname>
                            <given-names>Cynthia</given-names>
                        </name>
                        <aff>Manipal academy of higher education, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>3</day>
                    <month>3</month>
                    <year>2026</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>S. No.</bold>
                </p>
                <p> 
                    <bold>Reviewer&#x2019;s Comment</bold>
                </p>
                <p> 
                    <bold>Response to Reviewer</bold>
                </p>
                <p> 
                    <bold>Changes Made in Manuscript</bold>
                </p>
                <p> 
                    <bold>Page Number of Revision</bold>
                </p>
                <p> 1</p>
                <p> Reports already exist on anaerobic osteomyelitis. Tuberculosis may cause bone destruction allowing secondary colonization. What is novel here?</p>
                <p> We agree that anaerobic osteomyelitis has been reported. However, reports of mixed aerobic and anaerobic co-infection complicating microbiologically confirmed tubercular vertebral osteomyelitis (TVO) are exceedingly rare. Only one previously reported case describes secondary anaerobic infection in chronic TVO. Our cases highlight polymicrobial co-infection in confirmed spinal TB and emphasize diagnostic implications.</p>
                <p> Added an explicit novelty paragraph at the beginning of the Discussion clarifying rarity of mixed aerobic&#x2013;anaerobic co-infection in confirmed TVO and distinguishing our cases from prior reports.</p>
                <p> Page 6 (Beginning of Discussion section)</p>
                <p> </p>
                <p> 2</p>
                <p> Only two cases are reported. What is the main purpose? Lack of innovation in treatment options.</p>
                <p> The purpose of this case series is not to propose novel therapy but to reinforce diagnostic vigilance. We emphasize the importance of recognizing air&#x2013;fluid levels on imaging, foul-smelling intraoperative findings, and the need for routine anaerobic cultures even after confirmation of MTB.</p>
                <p> Inserted a paragraph explaining that the innovation lies in diagnostic strategy rather than therapeutic novelty, particularly in TB-endemic settings.</p>
                <p> Page 7 (After discussion on mixed flora)</p>
                <p> </p>
                <p> 3</p>
                <p> Is it necessary to study the sequence of tuberculosis and mixed infection?</p>
                <p> We acknowledge that the temporal sequence cannot be definitively established in this retrospective series. However, tubercular caseation and vascular compromise may create a hypoxic environment predisposing to secondary anaerobic colonization. Prospective studies are needed to clarify this relationship.</p>
                <p> Added a paragraph discussing plausible pathogenesis and acknowledged limitation regarding inability to establish sequence of infection.</p>
                <p> Page 7 (After predisposing factors paragraph)</p>
                <p> </p>
                <p> 4</p>
                <p> Is the background and progression of cases described in sufficient detail?</p>
                <p> Clinical details including symptoms, laboratory parameters, imaging findings, microbiology, treatment, and follow-up were provided. However, we have further clarified the clinical timeline and prior treatment history to improve narrative clarity.</p>
                <p> Expanded clinical timelines and clarified absence of predisposing factors and prior antibiotic exposure in case descriptions.</p>
                <p> Pages 4&#x2013;5 (Case 1 and Case 2 sections)</p>
                <p> </p>
                <p> 5</p>
                <p> Is sufficient discussion included regarding importance and relevance to future understanding of disease processes? (Reviewer: Partly)</p>
                <p> We have expanded the discussion to emphasize implications for TB-endemic settings, diagnostic red flags (air&#x2013;fluid levels, foul odour), and the importance of comprehensive microbiological evaluation to improve outcomes.</p>
                <p> Added a &#x201c;clinical implications&#x201d; paragraph highlighting need for routine aerobic and anaerobic cultures in selected TVO cases.</p>
                <p> Page 10 (Before Conclusion section)</p>
                <p> </p>
                <p> 6</p>
                <p> Is the conclusion balanced and justified? (Reviewer: Partly)</p>
                <p> We have moderated the language to avoid overstatement and now emphasize that our findings suggest heightened clinical suspicion rather than definitive conclusions.</p>
                <p> Revised wording in Conclusion to reflect balanced interpretation and acknowledge small sample size.</p>
                <p> Page 11 (Conclusion section)</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report123606">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.78143.r123606</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Rahmathulla</surname>
                        <given-names>Gazanfar</given-names>
                    </name>
                    <xref ref-type="aff" rid="r123606a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-0904-1840</uri>
                </contrib>
                <aff id="r123606a1">
                    <label>1</label>Department of Neurosurgery, University of Florida Health, University of Florida Health Jacksonville, FL, USA</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>22</day>
                <month>3</month>
                <year>2022</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2022 Rahmathulla G</copyright-statement>
                <copyright-year>2022</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport123606" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.74393.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>The authors present a case report on 2 cases of vetebral osteomyelitis of the lumbar and cervical spine where the patients have co-existing mycobacterial and aerobic/anerobic infections. Both cases had surgical intervention with short term reported good outcomes.</p>
            <p> </p>
            <p> Pros - interesting article discussing the presence of overlapping bacterial infections in vertebral osteomyelitis.</p>
            <p> </p>
            <p> Cons - short follow up, no discussion about the length of anti-TB medications used, absence of radiological follow-up.</p>
            <p> </p>
            <p> The authors can write their article in standard format of introduction, material / methods where they can note the consent requirement rather than before the discussion.</p>
            <p> </p>
            <p> The authors should expand their discussion to explain the duration of anti-TB treatment in the presence of treatment for other organisms, their follow-up strategy and explain how the patient could have got these poly organisms to infect the spine.</p>
            <p> </p>
            <p> In the MRI images for case 1, the descriptions can be more clear and detailed, as they only show the psoas abscess but would better serve the readers by focusing on the vertebral osteomyelitis components as well.</p>
            <p> </p>
            <p> The authors should place another table with literature discussing TB with other infections and all the papers available on this topic. There will not be many and hence this paper would then be strengthened.</p>
            <p> </p>
            <p> Grammatical changes required in different paragraphs.</p>
            <p>Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?</p>
            <p>No</p>
            <p>Is the background of the cases&#x2019; history and progression described in sufficient detail?</p>
            <p>Yes</p>
            <p>Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?</p>
            <p>Yes</p>
            <p>Is the conclusion balanced and justified on the basis of the findings?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Traumatic brain and spine injury, spinal surgery and associated pathology, brain tumors, radiosurgery</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment8938-123606">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Sukumar</surname>
                            <given-names>Cynthia</given-names>
                        </name>
                        <aff>Manipal academy of higher education, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>I have no competing interests.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>26</day>
                    <month>10</month>
                    <year>2022</year>
                </pub-date>
            </front-stub>
            <body>
                <p>The case report has been revised to include physical examination, diagnostic tests, details of treatment and clinical outcome. Additional radiological images have been included for case 1 to indicate spondylodiscitis.</p>
                <p> </p>
                <p> Literature search to find similar cases with tubercular vertebral osteomyelitis and anaerobic infection was also done and details included in the manuscript.</p>
            </body>
        </sub-article>
        <sub-article article-type="response" id="comment8939-123606">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Sukumar</surname>
                            <given-names>Cynthia</given-names>
                        </name>
                        <aff>Manipal academy of higher education, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>26</day>
                    <month>10</month>
                    <year>2022</year>
                </pub-date>
            </front-stub>
            <body>
                <p>APPROVED WITH RESERVATIONS</p>
                <p> </p>
                <p> The authors can write their article in standard format of introduction, material / methods where they can note the consent requirement rather than before the discussion.-
                    <bold> 
                        <underline>revised</underline>
                    </bold>
                </p>
                <p> </p>
                <p> The authors should expand their discussion to explain the duration of anti-TB treatment in the presence of treatment for other organisms, their follow-up strategy and explain how the patient could have got these poly organisms to infect the spine.-
                    <underline> 
                        <bold>Revised</bold>
                    </underline>
                </p>
                <p> </p>
                <p> In the MRI images for case 1, the descriptions can be more clear and detailed, as they only show the psoas abscess but would better serve the readers by focusing on the vertebral osteomyelitis components as well. 
                    <underline>- 
                        <bold>images included&#x00a0;</bold>
                    </underline>
                </p>
                <p> </p>
                <p> The authors should place another table with literature discussing TB with other infections and all the papers available on this topic. There will not be many and hence this paper would then be strengthened.</p>
                <p> </p>
                <p> Grammatical changes required in different paragraphs. 
                    <list list-type="bullet">
                        <list-item>
                            <p>Is the background of the cases&#x2019; history and progression described in sufficient detail?</p>
                            <p> Yes</p>
                        </list-item>
                        <list-item>
                            <p>Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?</p>
                            <p> No... 
                                <underline>
                                    <bold>Details provided in the revised manuscript</bold>
                                </underline>
                            </p>
                        </list-item>
                        <list-item>
                            <p>Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?</p>
                            <p> Yes</p>
                        </list-item>
                        <list-item>
                            <p>Is the conclusion balanced and justified on the basis of the findings?</p>
                            <p> Yes</p>
                        </list-item>
                    </list>
                </p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report121806">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.78143.r121806</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Maatallah</surname>
                        <given-names>Kaouther</given-names>
                    </name>
                    <xref ref-type="aff" rid="r121806a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-3765-3286</uri>
                </contrib>
                <aff id="r121806a1">
                    <label>1</label>Rheumatology Department, Med Kassab institute of orthopedics, Tunisia Faculty of medicine of Tunis, University Tunis el Manar, Manouba, Tunisia</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>10</day>
                <month>3</month>
                <year>2022</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2022 Maatallah K</copyright-statement>
                <copyright-year>2022</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport121806" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.74393.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>reject</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>These are two cases of tuberculosis of the spine complicated by aerobic and anaerobic infections. The first is lumbar spondylodiscitis in a young woman. A second case is a middle-aged man with C4-5 cervical spondylodiscitis. Both cases improved after receiving antibiotic treatment and decompression surgery.</p>
            <p> </p>
            <p> In both cases, the chest radiography findings were not detailed. In the first case, no MRI images showed spondylodiscitis.</p>
            <p> </p>
            <p> The reason for the surgical treatment is not justifiable since, in both cases, there was no motor deficit.</p>
            <p>Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?</p>
            <p>Partly</p>
            <p>Is the background of the cases&#x2019; history and progression described in sufficient detail?</p>
            <p>Yes</p>
            <p>Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?</p>
            <p>Partly</p>
            <p>Is the conclusion balanced and justified on the basis of the findings?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Rheumatology</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment8940-121806">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Sukumar</surname>
                            <given-names>Cynthia</given-names>
                        </name>
                        <aff>Manipal academy of higher education, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>26</day>
                    <month>10</month>
                    <year>2022</year>
                </pub-date>
            </front-stub>
            <body>
                <p>NOT APPROVED</p>
                <p> </p>
                <p> These are two cases of tuberculosis of the spine complicated by aerobic and anaerobic infections. The first is lumbar spondylodiscitis in a young woman. A second case is a middle-aged man with C4-5 cervical spondylodiscitis. Both cases improved after receiving antibiotic treatment and decompression surgery.</p>
                <p> </p>
                <p> In both cases, the chest radiography findings were not detailed. In the first case, no MRI images showed spondylodiscitis.- 
                    <underline>
                        <bold>MRI images included</bold>
                    </underline>
                </p>
                <p> </p>
                <p> The reason for the surgical treatment is not justifiable since, in both cases, there was no motor deficit. 
                    <list list-type="bullet">
                        <list-item>
                            <p>Is the background of the cases&#x2019; history and progression described in sufficient detail?</p>
                            <p> Yes</p>
                        </list-item>
                        <list-item>
                            <p>Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?</p>
                            <p> Partly - 
                                <underline>
                                    <bold>Details included</bold>
                                </underline>
                            </p>
                        </list-item>
                        <list-item>
                            <p>Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?</p>
                            <p> Partly - 
                                <underline>
                                    <bold>Discussion has been revised as per your suggestions</bold>
                                </underline>
                            </p>
                        </list-item>
                        <list-item>
                            <p>Is the conclusion balanced and justified on the basis of the findings?</p>
                            <p> Partly - 
                                <underline>
                                    <bold>Revised</bold>
                                </underline>
                            </p>
                        </list-item>
                    </list>
                </p>
            </body>
        </sub-article>
    </sub-article>
</article>
