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.
One-fourth of the world’s population has been infected with Mycobacterium tuberculosis (M.tb). Although interferon-gamma release assays (IGRAs) have been shown to be valid methods for identifying M.tb infection and auxiliary methods for diagnosis of active tuberculosis (TB), lower sensitivity and higher indeterminate rate were often detected among immunosuppressed patients. IP-10 was an alternative biomarker due to the higher expression level after M.tb antigen stimulation, but whether CXCL10 mRNA (the gene that transcribes for the IP-10 protein) can be used as a target for M.tb infection diagnosis was limited. Therefore, we aimed to evaluate the performance of a novel M.tb-specific CXCL10 mRNA release assay in diagnosis of M.tb infection. Suspected TB patients and healthy controls were prospectively recruited between March 2018 and November 2019 from three hospitals in China. CXCL10 mRNA release assay and traditional interferon-gamma release assay (T-SPOT.TB) were simultaneously performed on peripheral blood. Of the 1,479 participants enrolled in the study, 352 patients with definite TB and 153 healthy controls were analyzed. CXCL10 mRNA release assay provided a sensitivity of 93.9% (95% CI = 90.8–96.2%) and a specificity of 98.0% (95% CI = 94.3–99.6%) in the diagnosis of M.tb infection, respectively, while T-SPOT.TB gave a sensitivity of 94.5% (95% CI = 91.5–96.6%) and a specificity of 100% (95% CI = 97.6–100.0%) in the diagnosis of M.tb infection, respectively. The diagnostic performance of CXCL10 mRNA release assay was consistent with T-SPOT.TB, with a total coincidence rate of 95.0% (95% CI = 93.0–96.9%) and a Cohen’s kappa value of 0.89 (0.84–0.93, p < 0.001). However, among TB patients with HIV co-infection (n = 14), CXCL10 mRNA release assay presented significantly higher positive rate [92.9% (66.1–99.8%) vs. 61.5% (31.6–86.1%), p = 0.029] than those of T-SPOT.TB. These results suggested that M.tb-specific CXCL10 mRNA was a novel and useful target in the diagnosis of M.tb infection.
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