Successful Treatment of Intractable Tuberculous Peritonitis in a Woman with Chronic Kidney Allograft Dysfunction Using Contezolid Containing Regimen.

Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.

The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (CCL23 and CXCL5) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

Pharmacokinetics of Antituberculosis Drugs in Plasma and Cerebrospinal Fluid in a Patient with Pre-Extensive Drug Resistant Tuberculosis Meningitis.

Drug-resistant tuberculous meningitis (TBM) is the most devastating and critical form of extrapulmonary tuberculosis. Here, we present a case of a 45-year-old male with pre-extensive drug-resistant tuberculosis meningitis (pre-XDR-TBM). He underwent emergency surgery for the long-tunneled external ventricular drainage (LTEVD). Molecular test and phenotypic drug sensitivity test (DST) of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) showed that the isolate was resistant to both rifampin and fluoroquinolones. An anti-tuberculous regimen of isoniazid, pyrazinamide, cycloserine, moxifloxacin, clofazimine, and linezolid was tailored accordingly. We monitored the drug concentration in his plasma and CSF before (at 0-hour) and after anti-TB drugs administration (at 1-hour, 2-hour, 6-hour, and 12-hour) on 10th day after treatment initiation. We hope to provide reference values of drug exposures in plasma and CSF for patients with pre-XDR-TBM.

Pediatric isoniazid-resistant tuberculosis of the bone marrow manifesting as hemophagocytic syndrome: A case report.

Hemophagocytic syndrome (HPS) is a critical syndrome of ineffective hyperinflammatory immune response resulting in infiltration of lymphocytes and histiocytes in various organs. Causes can be hereditary or due to malignancy, autoimmune disease, or infection. HPS due to Mycobacterium tuberculosis is rare as only a handful of cases are reported, and they are mostly associated with severe disseminated tuberculosis (TB). We reported a 9-year-old boy with tuberculosis of the bone marrow accompanied with hemophagocytic syndrome. The patient presented with manifestation of HPS and had no respiratory symptoms or risk factors for TB but was later diagnosed of isoniazid-resistant TB in the bone marrow. He had a good outcome after receiving anti-TB drugs and corticosteroids on time. This case highlights that bone marrow might be a shelter for Mycobacterium tuberculosis. Concurrent testing for drug susceptibility in TB cases with an uncommon manifestation is recommended even for first episodes. Early diagnosis and etiological confirmation of the infection origin and appropriate treatment are essential to improve survival in this otherwise life-threatening condition.

A Rare Case of Post-Primary Tuberculosis Which Was Pathologically Diagnosed as Lipoid Pneumonia.

Case Presentation: The patient was a middle-aged housewife who had been using the household spray for a long time, and the main symptoms were cough and sputum production. Chest CT showed lobar ground-glass opacities (GGOs) with small patchy consolidation in the right middle lobe (RML), specifically, lung tissue pathology showed a large number of foamy cells and scattered multinucleated giant cells. The patient received empirical anti-infective treatment, but no clinical improvement was observed. Laboratory tests, including smears and cultures of sputum, blood and bronchoalveolar lavage fluid (BALF), did not provide clear evidence for pathogenic microorganisms. Therefore, the presumptive diagnosis was exogenous LP (ExLP). After 28 days of prednisone treatment, her symptoms improved, but 2 months later, she presented with a worsening cough, and the GGOs had progressed into lobar consolidation. Transbronchial lung biopsy (TBLB) culture showed mycobacterium tuberculosis (MTB), and lung tissue pathology showed granulomatous inflammation. After anti-tuberculosis treatment, the consolidation in the right middle lobe was gradually absorbed, along with a considerable symptom improvement. The final diagnosis of the patient was MTB infection with an endogenous lipoid pneumonia (EnLP)-like presentation. Conclusion: The current case highlights that the MTB infection should be considered when pathology shows LP accompanied by scattered multinucleated giant cells.

Clinical Evaluation of Active Tuberculosis-Related Deaths in Shenzhen, China: A Descriptive Study.

OBJECTIVE: The aim of this study was to assess active tuberculosis-related deaths in Shenzhen city of China to identify major causes of mortality in different age groups. PATIENTS AND METHODS: Medical records of mortality cases of patients with active TB diagnosed during 2013-2018 were reviewed. All TB deaths were classified into two broad age groups (the young group: 18-65 years old and the elderly group: >65 years old). Causes of death were analyzed based on medical records. RESULTS: A total of 279 mortality cases of active TB were reviewed during the study period. Among them, mean age was 54.0±20.5 years old; 80.6% (225/279) were male. There were 5.7% and 4.6% MDR/XDRTB patients in the young and elderly group. Newly treated TB accounted for 89.6% in the young group and 85.1% in the elderly group. Pulmonary TB was a major infection type in both groups (65.1% vs 77.0%). Advanced TB (23.4%) and HIV co-infection (20.8%) were the leading causes of deaths in the young group, but deaths in the elderly group were mostly associated with underlying diseases, including cardiovascular disease (52.9%), diabetes (33.3%), COPD (16.1%) and cancer (11.5%). Malnutrition was a significant condition in both groups (43.2% vs 35.6%). In terms of respiratory complications, bacterial infection was the leading comorbidity in both groups (27.1% vs 18.4%), followed by septic shock (18.2% vs 12.6%) and respiratory failure (12.0% vs 11.5%). There were no significant statistical differences between the two groups. CONCLUSION: Our findings suggest that screening for HIV co-infection and early diagnosis of TB is vital in lowering TB-related deaths in young patients. Most deaths in elderly TB patients were caused by underlying health conditions or complications other than TB.

Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.

The WHO's "Global tuberculosis report 2020" lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 108) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo, regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy. Clinical Trial Registration: (https://clinicaltrials.gov/ct2/results?cond=&term=NCT03575299&cntry=&state=&city=&dist=) ( NCT03575299).

Closure of pulmonary cavity of a multidrug-resistant tuberculosis patient with catheter insertion - A case report.

The treatment of multidrug-resistant tuberculosis (MDR-TB) relies heavily on optimal chemotherapy, but interventional therapies can be adopted as adjuvant treatment to speed up illness control and increase the cure rate. We present a case of a 31-year-old MDR-TB male patient with a massive pulmonary cavity in the right lower lung cured by chemotherapy with a catheter inserted in the cavity as adjuvant treatment. This case illustrated that early interventional therapy increases the treatment success rate for pulmonary MDR-TB patients with empyema and massive cavity without the need of major invasive surgery and consequently preserve lung functions.

Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.

BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

Activated pulmonary tuberculosis in a patient with melanoma during PD-1 inhibition: a case report.

BACKGROUND: PD-1 checkpoint inhibitors have shown a robust tumor response in the treatment of various cancers. Pembrolizumab is an anti-PD-1 checkpoint antibody approved for the treatment of unresectable or metastatic melanoma in more than 40 countries. Although autoimmune pneumonitis is considered a common immune-related adverse event of PD-1 inhibitors, only limited studies have assessed the development of opportunistic infections such as pulmonary tuberculosis (TB). CASE PRESENTATION: A patient with metastatic melanoma whose pulmonary TB was activated after administration of pembrolizumab for melanoma is reported. Anti-TB drugs were administered, followed by pembrolizumab (2 mg/kg, repeated every 28 days), which successfully cured the TB and achieved complete response for melanoma. CONCLUSION: Activated pulmonary TB was observed during the administration of pembrolizumab. It was safe and effective in the current patient to combine anti-TB drugs and PD-1 inhibitors. More importantly, screening pulmonary TB before administration of PD-1 inhibitors is recommended.

Tuberculosis bronchopleural fistula treated with atrial septal defect occluder.

Bronchopleural fistula (BPF) is an uncommon and potentially fatal complication of lobectomy or pneumonectomy, particularly in tuberculosis patients. It is associated with high mortality and its treatment remains a challenge. The development of plugging technology has led to the emergence of less invasive endobronchial methods for treating BPF. We describe the successful treatment of a multidrug-resistant tuberculosis patient with BPF using an occlusion device originally designed for transcatheter closure of an atrial septal defect. Follow-up over 10 months revealed maintenance of the repair without any recurrence. This novel technique can be effective for treating a tuberculosis patient with postoperative BPF.