IL-10 and TGF-ß1 may weaken the efficacy of preoperative anti-tuberculosis therapy in older patients with spinal tuberculosis.

Spinal tuberculosis is a common extrapulmonary type that is often secondary to pulmonary or systemic infections. Mycobacterium tuberculosis infection often leads to the balance of immune control and bacterial persistence. In this study, 64 patients were enrolled and the clinicopathological and immunological characteristics of different age groups were analyzed. Anatomically, spinal tuberculosis in each group mostly occurred in the thoracic and lumbar vertebrae. Imaging before preoperative anti-tuberculosis therapy showed that the proportion of abscesses in the older group was significantly lower than that in the younger and middle-aged groups. However, pathological examination of surgical specimens showed that the proportion of abscesses in the older group was significantly higher than that in the other groups, and there was no difference in the granulomatous inflammation, caseous necrosis, inflammatory necrosis, acute inflammation, exudation, granulation tissue formation, and fibrous tissue hyperplasia. B cell number was significantly lower in the middle-aged and older groups compared to the younger group, while the number of T cells, CD4+ T cells, CD8+ T cells, macrophages, lymphocytes, plasma cells, and NK cells did not differ. Meaningfully, we found that the proportion of IL-10 high expression and TGF-ß1 positive in the older group was significantly higher than that in the younger group. TNF-α, CD66b, IFN-γ, and IL-6 expressions were not different among the three groups. In conclusion, there are some differences in imaging, pathological, and immune features of spinal tuberculosis in different age groups. The high expression of IL-10 and TGF-ß1 in older patients may weaken their anti-tuberculosis immunity and treatment effectiveness.

Bilateral Endoscopic Debridement Combined with Local Antituberculosis Drugs for Thoracic Tuberculosis with Large Paravertebral Abscess: A Multicenter Study with 4-year Follow-Up.

BACKGROUND: Paravertebral abscess represents a prevalent manifestation of thoracic tuberculosis, often necessitating surgical intervention. In this study, we introduced a novel approach by employing bilateral endoscopic debridement (BED) to address large Paravertebral abscesses associated with thoracic tuberculosis, a method not previously proposed in the literature. The clinical efficacy was examined through a comprehensive 4-year follow-up. METHODS: We conducted a retrospective analysis on patients diagnosed with thoracic tuberculosis and paravertebral abscess who underwent BED combined with local antituberculosis drugs (BED + LAD) between February 2015 and February 2019. A total of 29 eligible patients (12 males and 17 females) with a median (interquartile ranges) of 59.0(16.5) years were included in the study. All patients received the BED + LAD treatment. After the surgery, the patients were treated with a 4-drug antituberculosis therapy (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol). All relevant indicators were meticulously recorded and analyzed. RESULTS: The surgical procedures were successfully completed for all subjects, with an average intraoperative bleeding volume of (25.2 ± 8.9) ml, an average surgical time of (68.4 ± 14.0) minutes, an average fluoroscopy frequency of (21.7 ± 8.2) times, an average hospital stay of (14.2 ± 4.3) days, and an average medication period of (42.1 ± 9.6) weeks. All subjects completed at least a 4-year follow-up period. At the final follow-up, ESR and CRP levels returned to normal, and there was no significant increase in the Cobb angle (P>0.05). CONCLUSIONS: The application of BED + LAD in the treatment of thoracic tuberculosis and paravertebral abscess proved to be a safe, effective, and feasible approach.

Healing Assessment of Spinal Tuberculosis: A Systematic Review.

OBJECTIVE: Deciding the healing end point in spinal tuberculosis (STB) remains a controversial topic. The current systematic review aims to address the controversy existing in the literature to find a comprehensive method to assess healing in STB. METHODS: A thorough literature search was carried out for studies with the assessment of healing parameters in STB. Data extraction was carried out manually, which included study characteristics and healing criteria evaluated in each study. RESULTS: Qualitative analysis of 8 included studies showed that healing parameters were described in 3 domains: clinical, hematologic, and radiologic response of the patient to antitubercular chemotherapy. Each domain included various individual parameters, with clinical and radiologic assessment criteria being used in most of the studies. Improvement in terms of pain, constitutional symptoms, weight gain, neurology; variation in erythrocyte sedimentation rate and C-reactive protein; and changes in radiography, magnetic resonance imaging, and positron emission tomography/computed tomography were found to be promising predictors in the assessment of healing. CONCLUSIONS: Radiologic response parameters emerged as the maximally used criteria to assess healing in STB. However, in the absence of any statistical analysis and an observed lag in radiologic response, the cumulative effect of all the parameters in 3 domains (clinical, hematologic, and radiologic) can be used to declare a spinal tubercular lesion nonhealing, healing, or healed.

Differential distribution of linezolid in diseased and nondiseased bones in patients with spinal tuberculosis.

BACKGROUND: Linezolid exhibits antibacterial activity against sensitive and drug-resistant strains of Mycobacterium tuberculosis. Knowledge on the distribution of linezolid in different types of bones in patients with spinal tuberculosis (TB) is lacking, which limits the pharmacokinetic and pharmacodynamic studies of linezolid. This study aimed to evaluate the distribution of linezolid in diseased and nondiseased bones in patients with spinal TB. METHODS: Spinal TB patients treated with linezolid-containing regimens and whose diseased and nondiseased bones were collected during surgery were enrolled retrospectively from January 2017 to February 2022. Blood, nondiseased bones, and diseased bones were collected simultaneously during the operation. Linezolid concentrations in the plasma, nondiseased bones, and diseased bones were subjected to high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Seven eligible spinal TB patients, including one rifampicin-resistant case, were enrolled. Following a 600 mg oral administration of linezolid before surgery, the median concentrations of linezolid in plasma, nondiseased bone, and diseased bone of the seven patients were 8.23, 1.01, and 2.13 mg/L, respectively. The mean ratios of linezolid concentration in nondiseased bones/plasma, diseased bones/plasma and diseased bones/nondiseased bones reached 0.26, 0.49, and 2.27, respectively. The diseased bones/plasma presented a higher mean ratio of linezolid concentration than nondiseased bones/plasma, and the difference was statistically significant (t = 2.55, p = 0.025). Pearson's correlation analysis showed the positively correlation of linezolid concentrations in diseased and nondiseased bones (r = 0.810, p = 0.027). CONCLUSIONS: Linezolid exhibits a higher concentration distribution in diseased bones than in nondiseased bones.

Pediatric and adult meningeal, parenchymal, and spinal tuberculosis: A neuroimaging review.

Neurotuberculosis is defined as a tuberculous infection of the meninges, brain parenchyma, vessels, cranial and spinal nerves, spinal cord, skull, and spine that can occur either in a localized or in a diffuse form. It is a heterogeneous disease characterized by many imaging appearances and it has been defined as "the great mimicker" due to similarities with many other conditions. The diagnosis of central nervous system (CNS) tuberculosis (TB) is based on clinical presentation, neuroimaging findings, laboratory and microbiological findings, and comprehensive evaluation of the response to anti-TB drug treatment. However, the absence of specific symptoms, the wide spectrum of neurological manifestations, the myriad of imaging findings, possible inconclusive laboratory results, and the paradoxical reaction to treatment make the diagnosis often challenging and difficult, potentially delaying adequate treatment with possible devastating short-term and long-term neurologic sequelae. Familiarity with the imaging characteristics helps in accurate diagnosis and may prevent or limit significantly morbidity and mortality. The goal of this review is to provide a comprehensive up-to-date overview of the conventional and advanced imaging features of CNS TB for radiologists, neuroradiologists, and pediatric radiologists. We discuss the most typical neurotuberculosis imaging findings and their differential diagnosis in children and adults with the goal to provide a global overview of this entity.

Randomized controlled trial of vitamin d supplementation on toll-like receptor-2 (tlr-2) and toll-like receptor-4 (tlr-4) in tuberculosis spondylitis patients.

BACKGROUND: Tuberculosis spondylitis accounts for approximately 50% of all cases of skeletal tuberculosis. Vitamin D plays a role in the immune system. Vitamin D helps in the activation of TLR-2 and TLR-4, which play a role in the process of tuberculosis infection. The objective of this study was to investigate the effect of oral supplementation with vitamin D on TLR-2 and TLR-4 levels in tuberculosis spondylitis patients. METHODS: The true Experiment Design Pretest-Posttest with Control Group (Pretest-Posttest with Control Group) was used for this research. TLR-2 and TLR-4 were measured by ELISA. Repeated ANOVA, ANOVA tests, and Kolmogorov-Smirnov normality tests on the SPSS program were used to statistically analyze the results. RESULT: In the dose groups of 10,000 IU and 5000 IU, significant increases in the levels of vitamin D, TLR-2, and TLR-4 were observed at weeks 4 and 8 (p < 0.05). In the control group, there was no significant increase. CONCLUSIONS: Vitamin D supplements can significantly increase TLR-2 and TLR-4 levels. Supplementation with vitamin D 10,000 IU/day for 8 weeks can increase vitamin D levels > 50 ng/dl to optimally act as an immunomodulator.

Evaluation of different diagnostic methods for spinal tuberculosis infection.

BACKGROUND AND PURPOSE: Tuberculosis (TB) is the most fatal infectious disease worldwide. Approximately 24.6% of tuberculosis cases are extrapulmonary and predominantly affect the spine. It is difficult to diagnose spinal TB (STB). We aimed to evaluate the diagnostic performance of the Mycobacteria Growth Indicator Tube (MGIT)-960 culture, T-SPOT.TB, Xpert Mycobacterium tuberculosis complex (MTB)/resistance to rifampin (RIF), and Metagenomic Next-Generation Sequencing (mNGS) to detect STB. METHODS: We assessed 126 patients presumed to have STB using these four methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using clinical diagnosis as a reference. RESULTS: Of the patients, 41 were diagnosed with STB and 85 with non-STB. In the STB group, the sensitivity, specificity, PPV, and NPV of the MGIT-960 culture were 29.3% (12/41), 100% (85/85), 100% (12/12), and 74.6% (85/114), respectively. The sensitivity, specificity, PPV, and NPV of T-SPOT.TB were 92.7% (38/41), 82.4% (70/85), 58.5% (31/53), and 95.9% (70/73), respectively. The sensitivity, specificity, PPV, and NPV of the Xpert MTB/RIF assay were 53.7% (22/41), 100% (85/85), 100% (22/22), and 81.7% (85/104), respectively. The sensitivity, specificity, PPV, and NPV of mNGS were 39.0% (16/41), 98.8% (84/85), 94.1% (16/17), and 77.1% (84/109), respectively. The sensitivity, specificity, PPV, and NPV of mNGS + Xpert MTB/RIF were 73.2% (30/41), 100% (85/85), 96.8% (30/31), and 72.0% (85/118), respectively. The sensitivity, specificity, PPV, and NPV of the mNGS + T-spot assay were 97.6% (40/41), 100% (85/85), 67.9% (38/56), and 75.9% (85/113), respectively. Moreover, the sensitivity, specificity, PPV, and NPV of T-spot + Xpert MTB/RIF were 95.1% (39/41), 100% (85/85), 72.2% (39/54), and 81.0% (85/105), respectively. CONCLUSIONS: T-SPOT.TB is the most effective method for diagnosing STB; however, Xpert MTB/RIF is more reliable and can detect RIF resistance. Clinicians can use mNGS to identify pathogens in patients with spinal infections; these pathogens appeared to be more meaningful in guiding the clinical management of patients in the non-STB group. The combination of Xpert MTB/RIF and mNGS can improve the early diagnosis rate and drug resistance detection, reduce the diagnostic cycle, and provide early targeted anti-TB treatment for patients with STB.

Retrospective Evaluation of Short-Course versus Traditional Preoperative Chemotherapy in Thoracolumbar Spinal Tuberculosis Patients.

BACKGROUND Thoracolumbar spinal tuberculosis is a severe form of extrapulmonary tuberculosis requiring precise management strategies. Traditionally, patients undergo a 2-4 week course of preoperative quadruple chemotherapy before surgery. However, recent clinical practices have begun exploring the potential of a short-course (1-7 days) intensive preoperative chemotherapy regimen. This study aims to examine and compare the clinical effectiveness of both approaches, offering critical insights into the optimal preoperative chemotherapy duration. MATERIAL AND METHODS In this retrospective analysis, we examined the clinical data from 123 patients with surgically treated thoracolumbar spinal tuberculosis. Patients were categorized into two groups based on the duration of preoperative chemotherapy: the short-course intensive chemotherapy group (n=53, 1-7 days) and the traditional quadruple chemotherapy group (n=70, 2-4 weeks). We gathered and compared the pertinent clinical data from both groups to ascertain differences in clinical efficacy. RESULTS All 123 patients underwent follow-up for a duration averaging 2.8±0.7 years. Five patients experienced postoperative recurrence. Patients reported significant pain alleviation and overall good clinical outcomes. Among patients with neurological dysfunction, neurological symptoms were ameliorated, and the implanted devices were found to be effective. Bony fusion was observed in all the bone grafting regions. CONCLUSIONS For patients suffering from thoracolumbar spinal tuberculosis exhibiting progressive neurological deterioration, surgical intervention is deemed feasible after a brief period (usually 1-7 days) of intensive preoperative antitubercular therapy. This finding suggests that short-course intensive preoperative chemotherapy may serve as a viable approach in managing such cases.

Topical streptomycin irrigation of lesions to prevent postoperative site infections in spinal tuberculosis: a retrospective analysis.

PURPOSE: In spinal tuberculosis surgery, topical administration of drugs to the lesion is a preventive treatment measure. The aim is to achieve better bacterial inhibition and to prevent complications. As one of the most common complications after spinal tuberculosis surgery, many factors can lead to surgical site infection (SSI). No definitive reports of local streptomycin irrigation of the lesion and SSI of spinal tuberculosis have been seen. This study analyzed data related to surgical site infections (SSI) after the treatment of spinal tuberculosis using this regimen. METHODS: In this study, 31 were in the observation group (streptomycin flush) and 34 in the control group (no streptomycin flush). All patients received the same standard of perioperative care procedures. General information, operative time, intraoperative bleeding, ESR and CRP at one week postoperatively, time on antibiotics, total drainage, days in hospital, incision infection rate and secondary debridement rate were compared between the two groups. RESULTS: Patients in both groups completed the surgery successfully. The ESR and CRP levels in the observation group were lower than those in the control group one week after surgery (p < 0.05); the duration of postoperative antibiotics and hospital stay were lower than those in the control group (p < 0.05); the incidence of SSI in the two groups was 5.88% and 6.45% respectively, with no significant difference (p > 0.05). CONCLUSION: The use of topical streptomycin irrigation of the lesion during surgical procedures for spinal tuberculosis had no significant effect on the incidence of SSI, however, it helped to control the level of infection in the postoperative period and reduced the length of time patients had to use postoperative antibiotics and the number of days they stayed in hospital. Future prospective randomised controlled trials in more centres and larger samples are recommended.

Multifocal tuberculosis in children: A case of spinal tuberculosis.

Multifocal tuberculosis (TB) accounts for up to one-third of all cases of TB and children are at higher risk for extrapulmonary TB than adults. Spinal TB is the regular form of skeletal TB. Spondylodiscitis TB represents 47%-94% of spinal TB. Cervical localization is rare but remains dangerous because of diagnostic difficulties and severe complications. We report a case of a 10-year-old Moroccan girl, bacille Calmette-Guerin vaccinated, with no medical history or trauma, parents and siblings are healthy and no contact with TB. The patient was complaining of neck pain, asthenia, and loss of weight for 1 year. During this period, she had been treated with analgesics and anti-inflammatory drugs, with no clinical evolution. The parents consulted the pediatric emergency room when they noticed a tumefaction in the middle thoracic region. Physical examination found a pectus carinatum deformity, palpable axillary, and submandibular lymph node, and a fixed palpable median thoracic mass fistulized to the skin. The GeneXpert MTB/RIF and QuantiFERON-TB Gold assay were positive. Chest computed tomography showed cervicodorsal spondylodiscitis staged at C5-D10, with abscessed perivertebral and peristernal collections, with epidural extension at C5-C6 and pleural level. The presence of an axillary lymph node with necrotic center. The skin biopsy showed a morphological appearance of epithelial and gigantocellular granulomatous inflammation. The patient had pharmacological treatment anti-TB drug with fixed-dose combination regimen and supportive therapy for pain management.

MMP9 and STAT1 are biomarkers of the change in immune infiltration after anti-tuberculosis therapy, and the immune status can identify patients with spinal tuberculosis.

BACKGROUND: Due to a lack of studies on immune-related pathogenesis and a clinical diagnostic model, the diagnosis of Spinal Tuberculosis (STB) remains uncertain. Our study aimed to investigate the possible pathogenesis of STB and to develop a clinical diagnostic model for STB based on immune cell infiltration. METHODS: Label-free quantification protein analysis of five pairs of specimens was used to determine the protein expression of the intervertebral disc in STB and non-STB. GO enrichment analysis, and KEGG pathway analysis were used to investigate the pathogenesis of STB. The Hub proteins were then eliminated. Four datasets were downloaded from the GEO database to analyze immune cell infiltration, and the results were validated using blood routine test data from 8535TB and 7337 non-TB patients. Following that, clinical data from 164 STB and 162 non-STB patients were collected. The Random-Forest algorithm was used to screen out clinical predictors of STB and build a diagnostic model. The differential expression of MMP9 and STAT1 in STB and controls was confirmed using immunohistochemistry. RESULTS: MMP9 and STAT1 were STB Hub proteins that were linked to disc destruction in STB. MMP9 and STAT1 were found to be associated with Monocytes, Neutrophils, and Lymphocytes in immune cell infiltration studies. Data from 15,872 blood routine tests revealed that the Monocytes ratio and Neutrophils ratio was significantly higher in TB patients than in non-TB patients (p < 0.001), while the Lymphocytes ratio was significantly lower in TB patients than in non-TB patients (p < 0.001). MMP9 and STAT1 expression were downregulated following the anti-TB therapy. For STB, a clinical diagnostic model was built using six clinical predictors: MR, NR, LR, ESR, BMI, and PLT. The model was evaluated using a ROC curve, which yielded an AUC of 0.816. CONCLUSIONS: MMP9 and STAT1, immune-related hub proteins, were correlated with immune cell infiltration in STB patients. MR, NR, LR ESR, BMI, and PLT were clinical predictors of STB. Thus, the immune cell Infiltration-related clinical diagnostic model can predict STB effectively.

Dual antituberculosis drugs-loaded gelatin hydrogel bioimplant for treating spinal tuberculosis.

Spinal tuberculosis (TB) represents around 1% of the recorded TB with a high mortality rate due to neurological complications and kyphosis. The current work aimed to develop a bioimplant scaffold to treat spinal TB disease. The scaffold is composed of a biocompatible semi-interpenetrating (semi-IPN) gelatin-based hydrogel incorporating mesoporous silica nanoparticles (MPS-NPs) loaded with rifampicin (RIF) and levofloxacin (LEV) to treat TB. The elastic modulus of the hydrogel was 7.18 ± 0.78 MPa. Minimum inhibitory concentrations (MIC) value against Mycobacterium bovis for LEV-loaded and RIF-loaded MPS-NPs were 6.50 and 1.33 µm/ml, respectively.Sequential release of drugs was observed after 15 days. Loading of the MPS-NPs in the hydrogel matrix governed the amount of released drugs by prolonging the period of release up to 60 days. WST-1 test confirmed the biocompatibility and safety of the developed vertebral hydrogel bioimplant. Histological and immunohistochemistry micrographs showed the progress in healing process with the bioimplant. Besides, loading of LEV and RIF in the implants declined the presence of the giant macrophages clusters as compared to control groups. All the obtained results support the potential use of the developed vertebral hydrogel bioimplant as a scaffold with good mechanical and biocompatible properties along with a good ability to eradicate the TB pathogen.

Spinal Tuberculosis within the Vertebral Arch Mimicking a Malignant Tumor: Case Report.

BACKGROUND: Spinal tuberculosis is a manifestation of extrapulmonary tuberculosis. The incidence of tuberculosis is low in high-income countries; however, globally, it still remains one of the most frequent fatal infectious diseases. Because of its rarity in developed countries, spinal tuberculosis can be mistaken for malignant tumors of the spine, especially in case of an atypical radiologic manifestation and without pulmonary affection. METHODS: We present the case of a 39-year-old man from South India with quickly progressing gait disturbance and hypesthesia below the Th10 level. Magnetic resonance imaging revealed an osteolytic lesion of the vertebral arch Th2 with central necrosis and compression of the spinal cord altogether highly suspicious for spinal metastasis. RESULTS: After surgical removal of the mass by laminectomy, the patient regained normal neurologic function. Histology revealed a severe granulomatous inflammation and DNAhybridization of polymerase chain reaction (PCR) products detected Mycobacterium tuberculosis-specific DNA in the sample. Biopsy of an enlarged hilar lymphnode allowed us to obtain material to successfully perform a drug resistance test to start specific antimicrobial therapy. CONCLUSION: Spinal tuberculosis, even with atypical radiologic appearance, has to be considered a differential diagnosis in patients with provenance from endemic countries. A multidisciplinary diagnostic approach helps perform antimicrobial susceptibility testing to avoid delaying the start of antibiotic therapy.

Disseminated Tuberculosis in an Immunocompetent State: A Case Report.

BACKGROUND: Tuberculosis is one of the major infectious diseases of mankind and remains a significant health concern, especially in developing countries. Clinical manifestations of TB are broad and sometimes very challenging for clinicians to diagnose early. Tuberculous psoas abscess was generally secondary to spinal tuberculosis or direct extension from adjacent structures in immunocompromised individuals, but tuberculous psoas abscess in the immunocompetent state is very infrequent. In addition, pancytopenia and new onset neck swelling simultaneously make this presentation a very unusual clinical entity in tuberculosis. CASE PRESENTATION: We now present a case of a 21-years-old, unmarried, otherwise healthy girl presented with fever, lower abdominal pain and weight loss for two months. She also noticed painless neck swelling for 15 days. She later had a tuberculous left sided psoas abscess with pancytopenia and a cold abscess on the left side of the neck with no sign of any other apparent focus, according to the evidence. Diagnosis of disseminated TB without lung involvement was established and ATT was started. The outcome was successful on follow up. CONCLUSION: Among the broad spectrum of atypical manifestations of TB, this case report draws attention to its rarity, diagnostic challenge and awareness of the clinical spectrum, especially in developing countries.

Effect of teriparatide on drug treatment of tuberculous spondylitis: an experimental study.

Tuberculous spondylitis often develops catastrophic bone destruction with uncontrolled inflammation. Because anti-tuberculous drugs do not have a role in bone formation, a combination drug therapy with a bone anabolic agent could help in fracture prevention and promote bone reconstruction. This study aimed to investigate the influence of teriparatide on the effect of anti-tuberculous drugs in tuberculous spondylitis treatment. We used the virulent Mycobacterium tuberculosis (Mtb) H37Rv strain. First, we investigated the interaction between teriparatide and anti-tuberculosis drugs (isoniazid and rifampin) by measuring the minimal inhibitory concentration (MIC) against H37Rv. Second, we evaluated the therapeutic effect of anti-tuberculosis drugs and teriparatide on our previously developed in vitro tuberculous spondylitis model of an Mtb-infected MG-63 osteoblastic cell line using acid-fast bacilli staining and colony-forming unit counts. Selected chemokines (interleukin [IL]-8, interferon γ-induced protein 10 kDa [IP-10], monocyte chemoattractant protein [MCP]-1, and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]) and osteoblast proliferation (alkaline phosphatase [ALP] and alizarin red S [ARS] staining) were measured. Teriparatide did not affect the MIC of isoniazid and rifampin. In the Mtb-infected MG-63 spondylitis model, isoniazid and rifampin treatment significantly reduced Mtb growth, and cotreatment with teriparatide did not change the anti-tuberculosis effect of isoniazid (INH) and rifampin (RFP). IP-10 and RANTES levels were significantly increased by Mtb infection, whereas teriparatide did not affect all chemokine levels as inflammatory markers. ALP and ARS staining indicated that teriparatide promoted osteoblastic function even with Mtb infection. Cotreatment with teriparatide and the anti-tuberculosis drugs activated bone formation (ALP-positive area increased by 705%, P = 0.0031). Teriparatide was effective against Mtb-infected MG63 cells without the anti-tuberculosis drugs (ARS-positive area increased by 326%, P = 0.0037). Teriparatide had no effect on the efficacy of anti-tuberculosis drugs and no adverse effect on the activity of Mtb infection in osteoblasts. Furthermore, regulation of representative osteoblastic inflammatory chemokines was not changed by teriparatide treatment. In the in vitro Mtb-infected MG-63 cell model of tuberculous spondylitis, cotreatment with the anti-tuberculosis drugs and teriparatide increased osteoblastic function.

Use of bedaquiline in spinal osteomyelitis and soft tissue abscess caused by multidrug-resistant Mycobacterium tuberculosis: A case report.

INTRODUCTION: Spinal Tuberculosis (STB) represents between 1% and 2% of total tuberculosis cases. STB management remains challenging; the first-line approach consists of medical treatment, while surgery is reserved for patients with complications. No data regarding STB treatment with bedaquiline-containing regimens are available in the literature. CASE DESCRIPTION: Herein, we report the case of a 21-year-old man from Côte d'Ivoire with a multidrug resistance STB with subcutaneous abscess. After approval of the hospital off-label drug committee, we started bedaquiline 400 mg daily for two weeks, followed by 200 mg three times per week, for 22 weeks, associated with linezolid 600 mg daily, rifabutin 450 mg daily, and amikacin 750 mg daily (interrupted after eight weeks). During treatment, we performed a weekly EKG. No QT prolongation was shown, but inverted T waves appeared, requiring several cardiological consultations and cardiac MRI, but no cardiac dysfunction was found. After 24 weeks, bedaquiline was replaced with moxifloxacin 400 mg daily. The patient continued treatment for another year. We performed another computer tomography at the end of treatment, confirming the cure. DISCUSSION: A salvage regimen containing bedaquiline proved effective in treating multidrug-resistance tuberculosis spinal infection without causing severe adverse effects. However, further studies are needed to evaluate better bedaquiline bone penetration and the correct duration of treatment with bedaquiline in MDR spinal tuberculosis.

Comparative efficacy of traditional conservative treatment and CT-guided local chemotherapy for mild spinal tuberculosis.

BACKGROUND: There are considerable differences in the treatment strategy for spinal tuberculosis, including conservative or surgical procedures. Conservative treatment is always suitable for most patients. This study aimed to compare the clinical efficacy of traditional conservative treatment with CT-guided local chemotherapy strategy of mild spinal tuberculosis. METHODS: This research retrospectively analysed 120 patients with spinal tuberculosis between January 2005 and January 2016 according to the diagnostic criteria of mild spinal tuberculosis. In total, 89 patients underwent traditional conservative treatment, 31 underwent CT-guided local chemotherapy. Clinical outcome, laboratory indexes, and radiological results were analysed to provide a clinical basis for the choice of mild spinal tuberculosis treatment. RESULTS: All cases achieved a clinical cure with 24 to 50 months followed up. Cobb angle of the two groups spinal tuberculosis segments was 6.25 ± 3.1100B0, 5.69 ± 2.5800B0 before treatment and 12.36 ± 6.3100B0, 14.87 ± 7.2600B0 after treatment, respectively. The VAS scores were significantly decreased post-treatment. At the 1 month follow-up, the VAS scores and erythrocyte sedimentation rate (ESR) were significantly differences between the two groups. The efficacy in the CT-guided local chemotherapy (Group B) was better than the traditional conservative treatment (Group A). But from the 3 months follow-up to the last follow-up, the VAS scores and ESR was no significant differences between the two groups and the average ESR decreased to normal. There was no evident kyphosis, symptoms or neurological deficits at the final follow-up. The paravertebral abscesses had disappeared, with no significant progression of local kyphosis, significant absorption and clear lesion edges, pain relief and normal ESR in the two groups. CONCLUSIONS: For mild spinal tuberculosis, traditional conservative treatment can achieve satisfactory results. The strategy combined with CT-guided local chemotherapy treatment is minimally invasive, beneficial for the drainage of paravertebral abscesses and pain relief.

A 27-Year-Old Woman Diagnosed with Tuberculous Spondylitis, or Pott Disease, During Pregnancy: A Case Report.

BACKGROUND Tuberculous spondylitis, or Pott disease, includes vertebral body osteomyelitis and intervertebral discitis following infection with Mycobacterium tuberculosis and can present with vertebral collapse and back pain. This report is of a 27-year-old woman diagnosed with tuberculous spondylitis, or Pott disease, during pregnancy. CASE REPORT A 27-year-old female, in her first pregnancy and at 29 weeks of gestation, presented to the Emergency Department with worsening severe neck and back pain for the past 5 months. Post-gadolinium contrast T1-weighted diffusion magnetic resonance imaging demonstrated multiple soft tissue spinal lesions (T2-T4). Computed tomography-guided biopsy showed a central caseous necrosis enclosed by a granuloma containing a wide array of cells comprising epithelioid cells, Langhans giant cells, lymphocytes, and plasma cells. Ziehl-Neelsen staining was positive for acid-fast bacilli. The final diagnosis was consistent with Pott disease. The patient received anti-tuberculosis medications, her symptoms improved over time, and she delivered vaginally at term. At a 16-month follow-up, her symptoms had improved, and she returned to her normal daily activities. There were no complications arising from the use of gadolinium contrast in the mother or toddler. CONCLUSIONS This report has highlighted the importance of imaging of the spine in the diagnosis of causes of severe back pain. This rare presentation of Pott disease in pregnancy has shown the challenges in diagnosis and the importance of a multidisciplinary approach to diagnosis and management so that treatment protects both the mother and fetus.

Evaluation of host biomarkers for monitoring treatment response in spinal tuberculosis: A 12-month cohort study.

BACKGROUND: Monitoring treatment response is an important precaution in spinal tuberculosis (TB), particularly when the condition was clinically diagnosed rather than bacteriologically confirmed and when drug susceptibility testing was not performed. Conventional monitoring measures have limitations and there is a need for favourable alternatives. Therefore, this study aimed to investigate changes in immune biomarkers over the course of treatment for spinal TB and to compare these responses to the conventional monitoring measure, erythrocyte sedimentation rate (ESR). METHODS: Patients with spinal TB were recruited from a tertiary hospital in the Western Cape, South Africa, and provided blood samples at 0, 3, 6, 9 and 12 months of TB treatment. Blood samples were analysed for ESR, using standard techniques, and for 19 cytokines, using a multiplex platform. Changes in ESR and cytokine levels were investigated using a mixed model ANOVA and Least Significant Difference post-hoc testing. RESULTS: Twenty-six patients with spinal TB were included in the study although only fifteen remained in follow-up at 12 months. Seven biomarkers changed significantly over the course of treatment (CRP, Fibrinogen, IFN-γ, Ferritin, VEGF-A, ApoA1 and NCAM, p < 0.01) with a further three showing a strong trend towards change (CCL1, CXCL9 and GDF-15, 0.05 ≥ p ≤ 0.06). Responsive biomarkers could be approximately grouped according to patterns of progressive, initial or delayed change. ESR performed similarly to CRP, Fibrinogen and IFN-γ with all showing significant decreases between 0, 6 and 12- months of treatment. Individual ESR responses were variable. DISCUSSION: Individual ESR responses may be unreliable and support the investigation of multi-marker approaches to evaluating treatment response in spinal TB. Biomarkers of treatment response identified in the current study require validation in a larger study, which may also incorporate aspects such as evaluating biomarkers within the first week of treatment and the inclusion of a healthy control group.