[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

Vitamin D receptor FokI gene polymorphism and tuberculosis susceptibility: a meta-analysis.

Numerous studies have evaluated the association between FokI polymorphisms in the vitamin D receptor (VDR) gene and tuberculosis risk. However, the specific association remains controversial. In this study, we performed a meta-analysis to assess the association between the VDR gene FokI polymorphism and tuberculosis. Published studies from the PubMed and Embase databases were retrieved. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effect models. Overall, a significant association was found between FokI polymorphism and tuberculosis risk when all studies were pooled (ff vs FF: OR = 1.36, 95%CI = 1.11-1.66; ff vs Ff: OR = 1.38, 95%CI = 1.14-1.67; dominant model: OR = 0.73, 95%CI = 0.61-0.88). In subgroup analysis by race, a significant association between FokI polymorphism and tuberculosis risk was observed in Asians (ff vs FF: OR = 1.71, 95%CI = 1.02-2.85; ff vs Ff: OR = 1.86, 95%CI = 1.40-2.47; dominant model: OR = 0.55, 95%CI = 0.42-0.72), and no significant association was observed among Caucasians and Africans. In conclusion, the FokI polymorphism in the VDR gene may be related to an increased risk of tuberculosis in Asians. Further large and well-designed studies are needed to confirm these conclusions.

[Direct optical resolution of acidic biphenyl drugs by high performance liquid chromatography on tris(3,5-dimethylphenylcarbamate) of cellulose].

A chiral stationary phase was prepared by coating cellulose-tris(3, 5-dimethylphenylcarbamate) onto aminopropylated silica gel. A series of enantiomeric acidic biphenyl drugs were directly resolved on the chiral stationary phase (CSP) by normal-phase high performance liquid chromatography (HPLC). A hexane-2-propanol eluting system containing 1% of trifluoroacetic acid was used as mobile phase. Efficient optical resolution of the acidic biphenyl drugs has been attained. The factors that influence chiral discrimination such as structural characeristic of the samples and mobile phase were investigated. An interaction model between the stationary phase and the samples was discussed. The results showed that efficient optical resolution of racemic carboxylic acids could be attained by normal-phase HPLC on CSP using a hexane-2-propanol eluting system containing 1% of trifluoroacetic acid.