关键词: 恶唑烷酮类, 结核,脑膜, 方案评价, 疗效比较研究

Abstract:

Objective To explore the efficacy and safety of the chemotherapy regimens with linezolid in the treatment of severe tuberculous meningitis. Methods A total of 167 patients with tuberculous meningitis were treated at the Chongqing Public Health Medical Center from January to December 2018. Among them, 33 patients were determined as severe tuberculous meningitis by using the criteria of the Medical Research Council (MRC) of UK. Those severe patients were divided into two groups according to whether they received linezolid for anti-tuberculosis (anti-TB) treatment or not: 16 patients received the chemotherapy regimens with linezolid and was called as the observation group; 17 patients received the conventional chemotherapy regimens without linezolid and was called as the control group. After 4 weeks treatment, the changes of the patients’body temperature, Glasgow (GCS) score and the indicators of cerebrospinal fluid in the two groups were compared and analyzed; at the same time, the side-effect of linezolid was also recorded. SPSS 17.0 software was used to carry out data statistical analysis; when the measurable data were in normal distribution, “$\bar{x}$±s” was used to illustrate it and t test was used for comparison; when the measurable data were in skew distribution, “median (quartile) (M(Q₁,Q₃))” was used to illustrate it and Wilcoxon rank sum test was used for comparison; the difference was statistically significant with P<0.05. Results On the 7th day of treatment, the average body temperature of the patients in the observation group decreased to (37.83±0.74) ℃, which was significantly lower than that of in the control group (38.49±0.87) ℃, the difference was statistically significant (t=-2.15, P=0.041). On the 10th day of treatment, the body temperature of the patients in the observation group returned to normal ((36.99±0.51) ℃) while the body temperature of the patients in the control group returned to normal ((36.93±0.76) ℃) on the 21st day of treatment. Before treatment, the GCS scores of the patients in the two groups were lower; after 2 weeks treatment, the GCS score of the patients in the observation group was (13.06±1.34) which was significantly higher than that in the control group (11.35±1.93), the difference was statistically significant (t=-2.99,P=0.006); after 4 weeks treatment, the GCS score of the patients in the observation group was (14.69±0.60) which was closed to 15 scores (GCS score <15 was regarded as consciousness disorder) and significantly higher than that in the control group (13.88±1.49), the difference was statistically significant (t=-2.01, P=0.050). In terms of the changes of CSF indicators, before treatment, the ratio of CSF glucose to synchronized blood glucose was 0.18 (0.05, 0.52) and the CSF protein quantification was 1.34 (0.60, 7.81) g/L in the observation group while those values were 0.28 (0.03, 0.52) and 1.81 (0.60, 2.53) g/L in the control group respectively, there were no significant differences between the two groups (Z=-0.90, P=0.368; Z=-0.18, P=0.857); after 4 weeks treatment, the ratio of CSF glucose to synchronized blood glucose was 0.61 (0.17, 6.00), which was significantly higher than that in the control group (0.33 (0.06, 0.79)); the CSF protein quantification in the observation group was 0.87 (0.35, 5.40) g/L which was significantly lower than that in the control group (0.97 (0.38, 3.71) g/L); the differences were statistically significant (Z=-3.35, P=0.001; Z=-3.17, P=0.002). Conclusion The chemotherapy with linezolid has advantages for the patients with severe tuberculous meningitis on controlling their body temperature, improving GCS score and improving some of cerebrospinal fluid indicators.

Key words: Oxazolidinones, Tuberculosis, meningeal, Program evaluation, Comparative effectiveness research