The chemotherapy of tuberculous meningitis in children and adults

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.