Identifying the Best Regimens for Treating Tuberculosis Isoniazid plus rifampicin following standard initial treatment prevents relapses

A 24-month follow-up study was conducted on 609 patients with pulmonary tuberculosis who had all received streptomycin, isoniazid, rifampicin and pyrazinamide for 2 months followed by 1 of the 4 following regimens: e isoniazid plus rifampicin for 4 months (n = 166) e isoniazid plus pyrazinamide for 4 months (n = 164) e isoniazid for 4 months (n = 156) e isoniazid for 6 months (n = 123).

Standard dosages were given for all drugs. Regimen 1 resulted in 4 relapses (3%) compared with 13 relapses (8%) in regimen 2 (p < 0.05) and 15

relapses (10%) in regimen 3 (p < 0.02). Regimen 4 also resulted in 4 relapses (3%). Side effects occurred in 15 patients during the initial 2 months of treatment with 3 patients needing modification of treatment. Three patients in both regimen 1 and 2 suffered adverse effects with 1 patient in regimen 1 needing a change of treatment. Two patients in both regimens 3 and 4 had adverse effects with 1 from each group requiring modified treatment. The efficacy of regimen 1 is confirmed in treating pulmonary tuberculosis. Isoniazid alone in the last 4 months resulted in a relapse rate of 10% which was reduced to 3% by an additional 2 months of treatment. East and Central Afncan;Bnt1sh Med1caf Research Counc1f Fifth Collaborative Study Tubercle 67 5·15. Mar 1986

Disease stage is more important than the regimen used in treating tuberculous meningitis. 180 children, aged 1-12 years, with tuberculous meningitis received 1 of the 3 following regimens for 12

months: e streptomycin 40 mgjkg, isoniazid 12-20 mgjkg, rifampicin 12 mgjkg. each daily for 2 months, then

ethambutol 17.5 mgjkg and isoniazid daily plus streptomycin twice weekly for 4 months, then ethambutol plus isoniazid daily for 6 months (n = 77)

e streptomycin plus isoniazid (12 mgjkg) plus rifampicin plus pyrazinamide 30 mgjkg daily for 2 months, then ethambutol plus isoniazid daily for 10 months (n = 29)

e streptomycin plus isoniazid plus pyrazinamide daily and rifamp1c1n twice weekly for 2 months then ethambutol plus isoniazid daily for 10 months (n = 74). There were 18 TB deaths in regimen 1 (26%) compared with 8 (33%) in regimen 2 and 18 (26%) in regimen

3. 23 patients (33%) in regimen 1 recovered fully compared witll 7 (29%) in regimen 2 and 25 (36%) in regimen 3. The stage of the d1sease on admission affected results with 78% of stage 1 (mild) patients fully recovering compared with 29% of stage 2 children and 7% of stage 3 (severe) patients. 14 patients developed hydrocephalus and 16 had varying degrees of optic disc pallor. In regimen 1, 11 of 39 patients (39%) who received high dose 1son1azid developed Jaundice compared w1th 8 of 49 (16%) given low dose isoniazid. Jaundice also occurred in 21% of patients in regimen 2 and 5% in regimen 3.

The choice of drug reg1men was of less consequence in determining outcome than the stage of illness when therapy commenced. However, because of the low hepatotoxicity in regimen 3 1t appears to be a su1table reg1men 1n treating children with tuberculous meningitis Ramachandran P Dura1pand1an M Nagara1on M Prabhakar R. Ramaknshnan CV. eta/ Tubercle 67 1729. Mar 1986

8 INPHARMA® 3 May 1986 0156-2703/86/1005·0008/0$01.00/0 © ADIS Press