儿童和成人结核性脑膜炎的化学疗法。

The chemotherapy of tuberculous meningitis in children and adults.

机构信息

Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa.

出版信息

Tuberculosis (Edinb). 2010 Nov;90(6):375-92. doi: 10.1016/j.tube.2010.07.003.

DOI:10.1016/j.tube.2010.07.003

PMID:20810322

Abstract

Literature dealing with antituberculosis chemotherapy of tuberculous meningitis (TBM) in adults and children is reviewed and recommendations made for the chemotherapy of TBM. Publications relating to the chemotherapy of TBM were reviewed which contribute to understanding the efficacy of different drugs and regimens in TBM treatment. The established classification of disease severity into stages I (no neurological signs and fully conscious), II (patients conscious but with neurological signs) and III (comatose or stuporous or with severe pareses) was used to compare regimens of isoniazid (INH), para-amino salicylic acid and streptomycin (INH regimens) used up to approximately 1970 with those using INH and rifampicin (RMP), supported by pyrazinamide and ethambutol or streptomycin (RMP regimens). Mortality in studies at all disease stages in adults or adults and children, with the children not distinguished, following INH regimens (12.4%, 25.2% and 55% at stages I, II and III respectively) did not differ significantly from that following introduction of RMP regimens (9.7%, 22.2% and 56% at stages I, II and III respectively), In studies of children only, mortality fell significantly following the introduction of RMP to 0%, 5.9% and 28.2% in children at stage I, II and III having been 10.2%, 22.3% and 49.4% respectively with INH regimens (P = 0.006). Following RMP regimens of 6 months duration, only 2 (1%) relapses occurred amongst 197 patients, after RMP regimens of 9-24 months only 1 (0.16%) relapse was recorded amongst 632 patients. Where INH resistance rates are <4% a directly observed INH, RMP, pyrazinamide and ethambutol for 2-months followed by INH and RMP for 4 months is recommended. If directly observed therapy cannot be practiced treatment duration should be extended to at least 9 months; if the risk of INH resistance or multidrug resistance is higher, the use of ethionamide and a fluoroquinolone and possibly cycloserine is recommended and pyrazinamide should be continued for full treatment duration. The penetration of RMP, ethambutol and streptomycin into cerebrospinal fluid is poor; higher dosages of RMP should be considered.

摘要

回顾了成人和儿童结核性脑膜炎（TBM）抗结核化学疗法的文献，并就 TBM 的化学疗法提出了建议。综述了与 TBM 化学疗法相关的出版物，这些出版物有助于了解不同药物和方案在 TBM 治疗中的疗效。使用已建立的疾病严重程度分类（分为 I 期（无神经体征且完全清醒）、II 期（患者清醒但有神经体征）和 III 期（昏迷或昏迷或严重瘫痪））来比较异烟肼（INH）、对氨基水杨酸和链霉素（INH 方案）的方案，直至大约 1970 年，以及使用 INH 和利福平（RMP）的方案，辅以吡嗪酰胺和乙胺丁醇或链霉素（RMP 方案）。在所有疾病阶段的成人或成人和儿童的研究中，未区分儿童，使用 INH 方案（I、II 和 III 期分别为 12.4%、25.2%和 55%）的死亡率与引入 RMP 方案（I、II 和 III 期分别为 9.7%、22.2%和 56%）无显著差异。在仅对儿童进行的研究中，随着 RMP 的引入，死亡率显著下降，在 I、II 和 III 期的儿童中分别为 0%、5.9%和 28.2%，而 INH 方案分别为 10.2%、22.3%和 49.4%（P=0.006）。在为期 6 个月的 RMP 方案后，在 197 名患者中仅发生 2 例（1%）复发，在为期 9-24 个月的 RMP 方案后，在 632 名患者中仅记录到 1 例（0.16%）复发。如果异烟肼耐药率<4%，建议直接观察异烟肼、RMP、吡嗪酰胺和乙胺丁醇 2 个月，然后异烟肼和 RMP 4 个月。如果不能进行直接观察治疗，则应延长治疗时间至少 9 个月；如果存在异烟肼耐药或耐多药的风险较高，则建议使用乙硫异烟胺和氟喹诺酮类药物，可能还需要环丝氨酸，并应继续使用吡嗪酰胺进行全程治疗。RMP、乙胺丁醇和链霉素进入脑脊液的能力较差；应考虑使用更高剂量的 RMP。