F1000ResearchF1000Research2046-1402F1000 Research LimitedLondon, UK10.12688/f1000research.74393.3Clinical Practice ArticleArticlesThe cocktail infection: anaerobic and aerobic co-Infections in tubercular vertebral osteomyelitis
[version 3; peer review: 2 approved with reservations, 3 not approved]
BhatShyamasunder NConceptualizationData CurationInvestigationMethodologyProject AdministrationResourcesSupervisionValidationWriting – Original Draft PreparationWriting – Review & Editinghttps://orcid.org/0000-0001-9545-48381KundangarRaghurajConceptualizationData CurationResourcesSupervisionWriting – Review & Editing1AmparNishanthData CurationFormal AnalysisMethodologyWriting – Review & Editinghttps://orcid.org/0000-0002-4696-71671SaitAnikaData CurationResourcesVisualizationWriting – Original Draft Preparationhttps://orcid.org/0000-0003-0159-01051ShenoyPadmaja AnanthData CurationFormal AnalysisResourcesSupervisionWriting – Original Draft Preparation1SukumarCynthia AmruthaConceptualizationData CurationInvestigationMethodologyWriting – Original Draft PreparationWriting – Review & Editinghttps://orcid.org/0000-0002-7026-2474a1SaravuKavithaConceptualizationMethodologyResourcesSupervisionWriting – Review & Editinghttps://orcid.org/0000-0001-6399-112912
Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
Manipal Centre for Infectious Diseases (MAC ID), PSPH, Manipal Academy of Higher Education, Manipal, Indiacynthiaamrutha@gmail.com
Background Anaerobic osteomyelitis is uncommon and rarely reported in association with tubercular vertebral osteomyelitis (TVO). In TB-endemic regions, identification of Mycobacterium tuberculosis may lead clinicians to overlook possible secondary polymicrobial infections.
Case Report We describe two immunocompetent adults with microbiologically confirmed TVO complicated by mixed aerobic and anaerobic co-infections. Both patients presented with chronic spinal pain and fever. MRI revealed spondylodiscitis with abscesses demonstrating air–fluid levels. Intraoperatively, foul-smelling pus was encountered. CBNAAT confirmed Mycobacterium tuberculosis in both cases. Concurrent aerobic and anaerobic organisms were isolated, including Escherichia coli, Streptococcus constellatus, Bacteroides fragilis, Peptoniphilus asachrolyticus, and Prevotella species. Patients improved with surgical decompression, anti-tubercular therapy, and targeted parenteral antibiotics.
Conclusion These cases highlight the potential for mixed aerobic and anaerobic co-infections complicating TVO. The presence of air–fluid levels on imaging and foul odor intraoperatively should raise suspicion for anaerobic involvement. Confirmation of tuberculosis should not preclude comprehensive microbiological evaluation. Heightened diagnostic vigilance may improve clinical outcomes in spinal tuberculosis.
Anaerobic osteomyelitisPrevotellaBacteroidesPeptostreptococcusspondylodiscitistuberculosis of SpineTubercular Vertebral OsteomyelitisThe author(s) declared that no grants were involved in supporting this work.Amendments from Version 2
Added an explicit novelty paragraph at the beginning of the Discussion clarifying rarity of mixed aerobic–anaerobic co-infection in confirmed TVO and distinguishing our cases from prior reports. Inserted a paragraph explaining that the innovation lies in diagnostic strategy rather than therapeutic novelty, particularly in TB-endemic settings. Added a paragraph discussing plausible pathogenesis and acknowledged limitation regarding inability to establish sequence of infection. Expanded clinical timelines and clarified absence of predisposing factors and prior antibiotic exposure in case descriptions. Added a “clinical implications” paragraph highlighting need for routine aerobic and anaerobic cultures in selected TVO cases. Revised wording in Conclusion to reflect balanced interpretation and acknowledge small sample size.
Introduction
Anaerobic organisms have been known to have an association with dental infections, bacteremia, endocarditis and soft tissue infections.
1 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.
1
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.
2 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’s spine). However, our cases highlight the rare isolation of gram-negative anaerobes (
Prevotella, Bacteroides, Peptoniphilus) from Tubercular vertebral osteomyelitis (TVO) in immunocompetent adults diagnosed with tuberculosis of spine.
Materials/Methods
Two cases of infectious spondylodiscitis have been presented in this case series.
Consent
Written informed consent for publication of their clinical details and/or clinical images was obtained from the patients.
Case reportCase 1
A 22-year-old poorly built (body mass index: 16 kg/m
2) 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 not received any prior antibiotic therapy before presentation to our institution. No prior spinal imaging had been performed elsewhere. The patient reported progressive worsening of pain and fever over the preceding four weeks, following which she sought care at our center and was evaluated with MRI and laboratory investigations within 48 hours of admission. She had no known co-morbidities. There was no significant genetic history given by the patient. She had no known co-morbidities. There was no significant genetic history given by the patient.
The patient denied any recent dental procedures, gastrointestinal interventions, trauma, or prior spinal surgery. He had not received prolonged or recent antibiotic therapy before admission. MRI evaluation and blood cultures were obtained within the first 24 hours of hospitalization, and surgical intervention was performed after imaging confirmed cord compression.
On examination, she was febrile (102° 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.
Lab investigations showed that she was anaemic (Haemoglobin of 8 g/dl). Her total counts were 13600/mm
3 (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.
A radiograph revealed mild lumbar scoliosis to the left side and bulky psoas muscle in the right side (
Figure 1a and
b).
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.
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 (
Figure 1c and
d). The spondylodiscitis can be appreciated in the
Figure 1e which shows post-contrast enhancement in L5-S1 vertebral discs.
Figure 1f shows the radiographs before treatment and after treatment for comparison.
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.
On the third hospital day CBNAAT report was suggestive of
Mycobacterium tuberculosis she was started on anti-tubercular therapy (ATT). The next day the aerobic culture grew
Escherichia coli whereas anaerobic culture grew
Bacteroids fragilis and
Peptoniphilus asachrolyticus. In addition, she was also started on injection Piperazillin-Tazobactem and oral tinidazole for 10 days. There was wound dehiscence on tenth postoperative day.
The repeat culture from the pus drained grew only
E. coli 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 anaemia 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.
Case 2
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.
The patient denied any recent dental procedures, gastrointestinal interventions, trauma, or prior spinal surgery. He had not received prolonged or recent antibiotic therapy before admission. MRI evaluation and blood cultures were obtained within the first 24 hours of hospitalization, and surgical intervention was performed after imaging confirmed cord compression.
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.
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 (
Figure 2a and
b).
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 (
Figure 2c and
d)
By this time the blood culture grew
Streptococcus constellatus and he was started on Injection ceftriaxone (2gm q24h) as per sensitivity report. His urine culture was sterile and Brucella agglutination test was negative.
He underwent anterior cervical decompression, by C5 corpectomy and fusion (
Figure 2e and
f
). 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.
The aerobic bacterial culture from the pus grew
Streptococcus constellatus with similar sensitivity as that of his blood culture. Anaerobic culture grew
Prevotella sps. The CBNAAT report was positive for
Mycobacterium tuberculosis. Histopathology confirmed granulation tissue with epitheloid cells and Langhans giant cells suggestive of tubercular osteomyelitis.
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.
Discussion
Anaerobic osteomyelitis was first reported in 1884 by Von Langenbeck in case of vertebral osteomyelitis.
3 Decades later, Taylor and Davies noted the presence of anaerobic organisms within sequestra in 55% of patients with chronic osteomyelitis.
4 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.
While anaerobic osteomyelitis has been described previously, reports of mixed aerobic and anaerobic co-infections complicating microbiologically confirmed tubercular vertebral osteomyelitis (TVO) are exceedingly rare. To our knowledge, only one case has described secondary anaerobic infection in chronic TVO. Our cases therefore highlight a distinct clinical entity — polymicrobial co-infection in confirmed spinal tuberculosis — which has important diagnostic implications in TB-endemic settings.
In a retrospective study done on osteomyelitis by Lewis
et al., it was found that 39 percent of patients with osteomyelitis had anaerobic infections.
1 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.
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
Prevotella 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
Bacteroides, Peptoniphilus (Peptotreptococcus) and
Clostridium with gram-negative
Pseudomonas aeruginosa isolated from a psoas abscess secondary to a chronic tubercular vertebral osteomyelitis.
In TB-endemic regions, once Mycobacterium tuberculosis is identified, clinicians may prematurely attribute the spinal infection solely to tuberculosis. Our cases emphasize that microbiological confirmation of TB does not exclude the possibility of concurrent polymicrobial infection. Failure to identify and treat these additional pathogens may delay recovery and increase postoperative complications.
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.
2 It is interesting to note that both our patients had no pre morbidities to predispose them to anaerobic osteomyelitis.
The absence of traditional predisposing factors in both patients suggests that tubercular tissue destruction itself may create a hypoxic, necrotic microenvironment conducive to secondary anaerobic colonization. Although the temporal sequence cannot be definitively established in this case series, tubercular caseation and vascular compromise may plausibly facilitate such polymicrobial superinfection.
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 found that the most common anaerobe implicated in osteomyelitis was
Bacteroides followed by
Peptostreptococcus and
Fusobacterium.
5 This trend was confirmed by a study by Ziment
et al. who found the most common isolate being
Bacteroides followed by
Peptostreptococcus and
Fusobacterium.
6 This similar trend of occurrence was noted in a large study done on 134 cases of pyogenic osteomyelitis by Haider
et al. between 1992 to 1993.
7 This trend agrees with our case of anaerobic osteomyelitis which showed a mixed anaerobic isolate of
Bacteroides with
Peptostreptococcus and
Clostridium.
A review of literature on available data on anaerobic osteomyelitis with
Prevotella isolates shows only nine cases reported till date.
8–16 Among this only one case reports secondary
Prevotella infection on chronic tubercular vertebral osteomyelitis. A summary of the data available on Anaerobic osteomyelitis with
prevotella isolates are shown in
Table 1.
Clinical characteristics of patients with
<italic toggle="yes">Prevotella</italic> isolated from vertebral osteomyelitis (previous data).
Authors
Age/sex
Level of osteomyelitis
Organism isolated
Risk factors
Clinical outcome
Surbled et al
8
44/M
L5-S1
P. melanogenica
none
Favourable
Salavert et al
9
27/F
L2-L3
P. melanogenica
IV drug use
Favourable
Fukuoka et al
10
60/M
T7-T8
P. intermedia
Age
Favourable
Schöber et al
11
45/F
L1-L2
P. intermedia
None
Favourable
Mukhyopadhyay et al
12
35/F
S1
P. melanogenica
Dental cleaning
Favourable
Salliot et al
13
62/M
L5-S1
Prevotella spp.
*
Age, steroids
Favourable
Purushothaman et al
14
74/F
L3-L4
Prevotella spp.
*
Age, ovarian malignancy
Favourable
Huang et al
15
73/F
T12-L3
P. melanogenica
Age, diabetes
Patient died
Goyal et al
16
68/F
T6-T8
P. oralis
Age, gastrointestinal procedure
Favourable
Species could not be identified.
Unlike previously reported cases of isolated anaerobic vertebral osteomyelitis, our patients demonstrated simultaneous isolation of Mycobacterium tuberculosis along with both aerobic and anaerobic bacteria. This microbiological constellation underscores the need for comprehensive culture techniques rather than reliance on a single pathogen identification.
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
17 where 29.5% of the cases were hematogenous and 32.8% were exogenous osteomyelitis. The study by Lewis
et al. also shows a preponderance towards exogenous osteomyelitis.
1
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.
18 The antibiotics were decided according to the sensitivity pattern noted on culture.
The key innovation in our report lies not in introducing novel treatment strategies, but in reinforcing a diagnostic approach. Recognition of radiological air–fluid levels and intraoperative foul odor prompted anaerobic cultures, which directly influenced antibiotic selection and duration. This diagnostic vigilance may be particularly important in resource-limited, TB-endemic settings.
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.
Clinical implications
In patients with TVO presenting with air–fluid levels on imaging or foul-smelling pus intraoperatively, clinicians should routinely request aerobic and anaerobic cultures even after confirmation of tuberculosis. Early recognition and targeted therapy may improve clinical outcomes.
Conclusion
Tubercular vertebral osteomyelitis is often considered a singular diagnostic entity; however, our cases suggest that concurrent aerobic and anaerobic co-infections may occur and should be considered in selected patients. The presence of air–fluid levels on imaging and foul-smelling pus intraoperatively may raise suspicion for anaerobic involvement.
Although limited by the small sample size and retrospective nature of this case series, our findings underscore the importance of comprehensive microbiological evaluation in patients with spinal tuberculosis. Heightened clinical suspicion and appropriate culture techniques may facilitate targeted therapy and potentially improve outcomes.
Patient perspective
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.
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.
Data availability
This is a report of 2 cases. There is no associated data available.
Acknowledgement
We acknowledge Manipal Academy of Higher Education, Manipal for its support in publishing the manuscript.
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1839292210.1007/s00776-007-1207-110.5256/f1000research.197355.r471148Reviewer response for version 3SohalJagdip Singh1Refereehttps://orcid.org/0000-0003-4797-9466
Centre for Vaccines and Diagnostic Research (CVDR), Chandigarh University, Gharuan, Mohali, Punjab, India
Competing interests: No competing interests were disclosed.
This is an excellent study and may be accepted after a major revision:
1. Authors have not used proper scientific nomenclature for the names of microorganisms (names of the microorganisms should be italics)
2. Abstract needs to rewritten describing the purpose behind the study, brief methos, results and proper concluding remarks based on the findings.
3. Insufficient information in the Introduction section, requires proper review of literature.
4. Manuscript should be written in proper scientific language (all sections).
5. Proper sequential events of the study should be included in Case reports (like authors are describing MRI findings before radiological findings).
6. Ethical approval details are not provided
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
No
Is the background of the cases’ history and progression described in sufficient detail?
No
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Partly
Is the conclusion balanced and justified on the basis of the findings?
Partly
Reviewer Expertise:
Mycobacterial infections, Molecular Epidemiology Vaccinology, Immunology, Molecular Biology, Microbial Genetics and Point of Care Diagnostics
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.
10.5256/f1000research.197355.r471150Reviewer response for version 3SinghSarman1Refereehttps://orcid.org/0000-0002-0749-9647
Advanced Centre for Chronic and Rare Diseases, New Delhi, India
Competing interests: No competing interests were disclosed.
The title of the article is vague and could have been written better.
The manuscript presents a series of cases on osteomyelitis; however, there are several substantial concerns regarding scientific accuracy, clinical reasoning, and overall manuscript quality. These issues must be carefully addressed before the work can be considered further.
Incorrect Statement on Rarity of Anaerobic Osteomyelitis:
The authors state that anaerobic osteomyelitis is “very rare,” which is misleading and factually inaccurate. A focused literature search using appropriate keywords will reveal multiple reported cases, including recent descriptions such as those by Zachary C Culley et al. (Cureus, 2026). The authors are advised to revise this statement and provide a balanced review of existing literature.
Inconsistencies and Interpretation of Laboratory and Imaging Data:
There appear to be inconsistencies and possible mix-ups in the laboratory data presented. More importantly, the MRI findings reportedly demonstrate “abscess with air–fluid levels,” which are highly suggestive of pyogenic or anaerobic infection. In such a scenario, the rationale for considering tuberculosis in the differential diagnosis is questionable. The authors should justify this clinical decision-making process, as it raises concerns regarding both resource utilization and application of clinical judgment.
Questionable Clinical History and Source of Infection:
The MRI findings also indicate soft tissue involvement. This raises concerns about the reliability and completeness of the clinical history. It is plausible that these patients may have received prior local injections, invasive procedures, or topical treatments (including corticosteroids), predisposing them to secondary infection. If the authors are proposing tubercular vertebral osteomyelitis (TVO), robust evidence must be provided. Additionally, the possibility of sample contamination or secondary infection should be explicitly addressed, along with the methods used to rule this out.
Lack of Microbiological and Follow-up Data:
The manuscript lacks critical microbiological details. There is no mention of nucleic acid amplification testing (NAAT) results, particularly rifampicin resistance status, which is essential in current tuberculosis diagnostics. Furthermore, no follow-up data are provided, making it difficult to assess treatment response or confirm the initial diagnosis.
Errors in Patient Description:
There are basic inconsistencies in the manuscript, including incorrect and interchangeable use of gender pronouns (he/she) for the first patient. Such errors reflect inadequate manuscript preparation and must be corrected.
Overall Presentation and Clinical Rigor:
The manuscript, in its current form, is poorly structured and lacks clarity. More importantly, it reflects gaps in clinical reasoning and diagnostic justification. The authors should substantially revise the manuscript to improve scientific rigor, ensure internal consistency, and provide a clearer, evidence-based narrative for each case.
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Partly
Is the background of the cases’ history and progression described in sufficient detail?
Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
No
Is the conclusion balanced and justified on the basis of the findings?
Partly
Reviewer Expertise:
Bacteriology, Tuberculosis and Chronic Diseases
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.
10.5256/f1000research.140334.r182021Reviewer response for version 2XuYongqing1Referee
Hospital of the Joint Logistics Support Force of the PLA, Kunming, China
Competing interests: No competing interests were disclosed.
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:
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;
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
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
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Yes
Is the background of the cases’ history and progression described in sufficient detail?
No
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Partly
Is the conclusion balanced and justified on the basis of the findings?
Partly
Reviewer Expertise:
Osteomyelitis，microsurgery
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.
SukumarCynthiaManipal academy of higher education, India
Competing interests: No competing interests were disclosed.
332026
S. No.
Reviewer’s Comment
Response to Reviewer
Changes Made in Manuscript
Page Number of Revision
1
Reports already exist on anaerobic osteomyelitis. Tuberculosis may cause bone destruction allowing secondary colonization. What is novel here?
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.
Added an explicit novelty paragraph at the beginning of the Discussion clarifying rarity of mixed aerobic–anaerobic co-infection in confirmed TVO and distinguishing our cases from prior reports.
Page 6 (Beginning of Discussion section)
2
Only two cases are reported. What is the main purpose? Lack of innovation in treatment options.
The purpose of this case series is not to propose novel therapy but to reinforce diagnostic vigilance. We emphasize the importance of recognizing air–fluid levels on imaging, foul-smelling intraoperative findings, and the need for routine anaerobic cultures even after confirmation of MTB.
Inserted a paragraph explaining that the innovation lies in diagnostic strategy rather than therapeutic novelty, particularly in TB-endemic settings.
Page 7 (After discussion on mixed flora)
3
Is it necessary to study the sequence of tuberculosis and mixed infection?
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.
Added a paragraph discussing plausible pathogenesis and acknowledged limitation regarding inability to establish sequence of infection.
Page 7 (After predisposing factors paragraph)
4
Is the background and progression of cases described in sufficient detail?
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.
Expanded clinical timelines and clarified absence of predisposing factors and prior antibiotic exposure in case descriptions.
Pages 4–5 (Case 1 and Case 2 sections)
5
Is sufficient discussion included regarding importance and relevance to future understanding of disease processes? (Reviewer: Partly)
We have expanded the discussion to emphasize implications for TB-endemic settings, diagnostic red flags (air–fluid levels, foul odour), and the importance of comprehensive microbiological evaluation to improve outcomes.
Added a “clinical implications” paragraph highlighting need for routine aerobic and anaerobic cultures in selected TVO cases.
Page 10 (Before Conclusion section)
6
Is the conclusion balanced and justified? (Reviewer: Partly)
We have moderated the language to avoid overstatement and now emphasize that our findings suggest heightened clinical suspicion rather than definitive conclusions.
Revised wording in Conclusion to reflect balanced interpretation and acknowledge small sample size.
Page 11 (Conclusion section)
10.5256/f1000research.78143.r123606Reviewer response for version 1RahmathullaGazanfar1Refereehttps://orcid.org/0000-0002-0904-1840
Department of Neurosurgery, University of Florida Health, University of Florida Health Jacksonville, FL, USA
Competing interests: No competing interests were disclosed.
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.
Pros - interesting article discussing the presence of overlapping bacterial infections in vertebral osteomyelitis.
Cons - short follow up, no discussion about the length of anti-TB medications used, absence of radiological follow-up.
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.
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.
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.
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.
Grammatical changes required in different paragraphs.
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
No
Is the background of the cases’ history and progression described in sufficient detail?
Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Yes
Is the conclusion balanced and justified on the basis of the findings?
Yes
Reviewer Expertise:
Traumatic brain and spine injury, spinal surgery and associated pathology, brain tumors, radiosurgery
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.
SukumarCynthiaManipal academy of higher education, India
Competing interests: I have no competing interests.
26102022
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.
Literature search to find similar cases with tubercular vertebral osteomyelitis and anaerobic infection was also done and details included in the manuscript.
SukumarCynthiaManipal academy of higher education, India
Competing interests: No competing interests.
26102022
APPROVED WITH RESERVATIONS
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.-
revised
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.-
Revised
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.
-
images included
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.
Grammatical changes required in different paragraphs.
Is the background of the cases’ history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
No...
Details provided in the revised manuscript
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Yes
Is the conclusion balanced and justified on the basis of the findings?
Yes
10.5256/f1000research.78143.r121806Reviewer response for version 1MaatallahKaouther1Refereehttps://orcid.org/0000-0003-3765-3286
Rheumatology Department, Med Kassab institute of orthopedics, Tunisia Faculty of medicine of Tunis, University Tunis el Manar, Manouba, Tunisia
Competing interests: No competing interests were disclosed.
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.
In both cases, the chest radiography findings were not detailed. In the first case, no MRI images showed spondylodiscitis.
The reason for the surgical treatment is not justifiable since, in both cases, there was no motor deficit.
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Partly
Is the background of the cases’ history and progression described in sufficient detail?
Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Partly
Is the conclusion balanced and justified on the basis of the findings?
Partly
Reviewer Expertise:
Rheumatology
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.
SukumarCynthiaManipal academy of higher education, India
Competing interests: No competing interests
26102022
NOT APPROVED
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.
In both cases, the chest radiography findings were not detailed. In the first case, no MRI images showed spondylodiscitis.-
MRI images included
The reason for the surgical treatment is not justifiable since, in both cases, there was no motor deficit.
Is the background of the cases’ history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Partly -
Details included
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Partly -
Discussion has been revised as per your suggestions
Is the conclusion balanced and justified on the basis of the findings?