Background: The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors. Methods: We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant. Results: Most patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045). Conclusions: The main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.

This study aims to investigate the clinical features and prognostic outcomes of pediatric tuberculosis (TB) in Shenzhen. This retrospective study collected demographic, clinical, laboratory, and prognostic data from pediatric patients diagnosed with TB between January 2013 and January 2023. Multivariable regression identified risk factors for loss to follow-up and mortality. A total of 358 children were included, and distinct age-related patterns were observed. Younger children had more extrapulmonary TB, whereas older children were more likely to develop pulmonary cavities. Nearly half (47.6%) of the children aged 0-1 years were household contacts of patients with TB, but none of the children had received TB preventive treatment before disease onset. Infants showed the highest rates of drug-induced liver injury (31%) and mortality (13.3%). Microbiological diagnosis was associated with reduced risk of loss to follow-up before treatment completion (hazard ratio 0.463, 95% confidence interval 0.248-0.863, P = 0.015). Tuberculous meningitis significantly increased mortality risk (hazard ratio 10.830, 95% confidence interval 1.214-96.645, P = 0.033). Pediatric TB presents with diverse clinical features across age groups. Early microbiological diagnosis and attention to high-risk populations, especially infants and those with TB meningitis, are essential for improving treatment outcomes. TB preventive treatment in exposed children remains critically underused.

This study aimed to compare the clinical profiles and maternal-foetal outcomes of tuberculosis (TB) disease in pregnant women following in vitro fertilization and embryo transfer (IVF-ET) versus natural conception (NC), and identify the associated high-risk factors. A retrospective analysis included 133 pregnant women with TB disease, stratified into IVF-ET (n = 16) and NC (n = 117) groups. Clinical, radiological, and laboratory parameters were evaluated, and logistic regression identified risk factors for stillbirth or preterm birth. The IVF-ET group exhibited significantly more severe TB manifestations, including higher rates of bilateral pulmonary lesions (100.0% vs 39.3%), miliary TB (93.8% vs 5.1%), and TB meningitis (37.5% vs 3.4%), alongside prolonged hospitalization (median 18.0 vs 9.0 days, P < 0.001). These patients also demonstrated lower lymphocyte, CD4, and CD3 cell counts, as well as lower plasma albumin levels. Adverse foetal outcomes were more frequent in the IVF-ET group (stillbirth: 62.5% vs 1.7%; preterm birth: 31.2% vs 8.5%, both P < 0.001). IVF-ET was the strongest independent predictor of adverse outcomes (adjusted OR=59.42, P = 0.002), with the predictive model achieving an AUC of 0.868 (optimism-corrected AUC of 0.817). Tuberculosis following IVF-ET is associated with exacerbated disease severity and adverse foetal outcomes, accompanied by reduced cellular immune status and a poorer nutritional-inflammatory profile at presentation (e.g., lower CD3+/CD4+ T-cell counts and albumin levels). Pre-IVF TB screening and heightened vigilance during pregnancy are critical for risk mitigation.

This study aimed to map the cerebrospinal fluid (CSF) molecular landscape across distinct stages of tuberculosis progression and to identify multi-omics signatures associated with tuberculous meningitis (TBM). Integrated proteomic and metabolomic profiling of CSF from 17 patients representing three disease stages: pulmonary tuberculosis (TB), hematogenous disseminated tuberculosis (HDTB), and disseminated tuberculosis with concomitant tuberculous meningitis (HDTB+TBM) were performed. Quantitative proteomics and non-targeted metabolomics were combined with pathway enrichment and network-based analyses to delineate stage-specific molecular alterations. CSF multi-omics profiling revealed modest molecular changes between TB and HDTB, but a marked and coordinated remodeling during the transition from HDTB to TBM. Compared with the HDTB+TBM group, the TB group exhibited 546 upregulated and 410 downregulated proteins, together with 80 differentially abundant metabolites. Integrated analyses converged on glycolysis/gluconeogenesis, pentose phosphate metabolism, and extensive O- and N-glycan biosynthesis pathways, indicating coupled metabolic and glycosylation rewiring during meningeal involvement. Six proteins (ENO2, LDHB, GALNT7, MAN1C1, PGD, and B4GALT1) emerged as a biologically coherent signature distinguishing TBM from non-meningeal tuberculosis. This study maps the molecular trajectory from tuberculosis to disseminated disease and tuberculous meningitis, identifying TBM as a distinct neuro-immune-metabolic state and providing a framework for mechanism-informed biomarker development.

Diagnosis of intracranial tuberculoma remains a challenge due to its rarity, non-specific clinical presentation, and radiological findings. Herein, we describe a case of intracranial tuberculomas in a male diabetic patient who presented headache and vomiting on admission. Neuroimaging findings indicated multiple ring contrast-enhanced lesions with extensive perilesional edema. However, a cerebrospinal fluid (CSF) examination was normal. When a biopsy of brain lesions was performed, pathological characteristics of tuberculosis were absent and acid-fast staining was negative. A tuberculosis diagnosis was subsequently obtained from an Xpert MTB/RIF Ultra assay of formalin-fixed paraffin-embedded brain tissue. The patient was treated with an optimized anti-tuberculosis regimen which included high-dose intravenous administration of rifampicin and isoniazid, and oral administration of linezolid. The patient recovered well and exhibited marked clinical improvement. This case report demonstrates that when CSF analysis does not indicate the presence of intracranial tuberculomas, analysis of formalin-fixed paraffin-embedded brain tissue specimens with the Xpert MTB/RIF Ultra assay may be able to confirm a diagnosis. Furthermore, a high dose of rifampicin and isoniazid plus linezolid may improve patient outcome.