Tbe .. apv Drug regimens for the treatment of tuberculosis A 6-month, largely twice-weekly, regimen appears safe and beneficial •••

125 evaluable patients with known or suspected pulmona~ and extrapulmonary t~berc~I?SIS were given oral isoniazid 300mg, nfamplcm 600mg. pyrazinamide 1.5-2.5g and 1M streptomycin 0.75-1g daily for 2 weeks, isoniazid IS mg/kg. rifampicin 6OOmg. pyrazinamide 3-4g and streptomycin 1-I.Sg twice-weekly (except rifampicin) for an additional 6 weeks, then isoniazid IS mg/kg and rifampicin 600mg twice­weekly for a further 18 weeks.

There were no treatment failures and only 2 relapses of pulmonary tuberculosis. occurring at 6 and S6. months !lfter the completion of therapy. respectively. ThiS treatment regimen was associated with relatively low toxicity; cutaneous abnormalities (including erythema. rash and pruritus) and moderate to severe nausea occurred in ~ and 4% of patients, respectively. 64% of all patIents had elevated uric acid levels, which returned to baseline after withdrawal of pyrazinamide. Elevation of liver enzymes occurred more frequently in alcoholic patients compared with nonalcoholic patients. Isoniazid resistance necessitated withdrawal of isoniazid in 7 patients and streptomycin was withdrawn from 2 patients because of resistance in 1 and possible toxicity in the other.

This study confirms other reports of the efficacy of 6-month regimens for the treatment of ~ube~losis, however, by introducing mtermlttent ~herapy. after only 2 weeks. this very low dose regtmen still proved to be efficacious; direct treatment supervision probably influenced patient compliance and treatment results. [See also Viewpoints section, this issue, p2] Cohn DL. Catlin BJ. Peterson KL. Judson FN. Sbarbaro JA. A 62-dose. 6-month therapy for pulmonary and extrapulmonary tuberculosis. A twiee-weekly. directly observed. and cost-effective regimen. Annals of Internal Medicine 112: 407-415, 15 Mar 1990 26l'I

0156-170J/90/0407-0007/0S01.00/0 © ADIS Plus

••• and a 6-moDth daily regimeD compares favourably with a 9-moDth daily regimeD

A 6-month antituberculous daily regimen containing isoniazid and rifampicin and pyrazinamide (for the first 2 months) was compared with a 9-month daily regimen containing isoniazid and rifampicin in patients with pulmonary tuberculosis in an open multicentre study; ethambutol was added to the regimen in cases of isoniazid resistance.

Of 617 patients assigned to the 6-month regimen, 94.6% had bacteriological conversion of sputum cultures by week 16 of therapy vs 89.9% of patients (n = 44S) receiving the 9-month regimen. Although rates of suspected adverse dru~ reactio~s .were significantly higher among pattents receiVIng the 6-month regimen between weeks 4-13 and 17-19, by the end of therapy the rates were not significantly different between treatment groups (7.7 vs 6.4% for 6-and 9-month regimens, respectively); similar rates of hepatotoxic reactions were reported (1.6 vs 1.2% respectively), while significantly more patients ' receiving the 6-month regimen had elevated uric acid levels.

Noncompliance rates were similar for the first 24 weeks of therapy, however, by the end of the~py significantly more 9-month regimen reclplents had been noncompliant (29.2% vs .16.8% ~f 6-month. patients); duration of therapy lS a major d:et~rmmant of compliance. Relapse rates were SimIlar between both patient groups 96 weeks after completing therapy. Successful treatment, defined by completion of at least 80% of medication, bacteriological sputum conversion by week 16 of therapy and no adverse reaction relapse or interruption of therapy for > 14 ' consecutive days, was reported in significantly more 6- vs 9-month regimen recipients (61.4 vs 50.6%).

Results from this non-blinded, randomised, study suggest that the 6-month regimen is at least as efficacious and. safe as the 9-month regimen, and m~re CO~duclve .to patient compliance. [See also. V,ewpomts sectIOn, this issue, p2] Combs DL. O'Brien RJ. Gerter U. USPHS tuberculosis shon-course chemotherapy trial 21: elTectiveness. toxicity. and acceptability. The repon of final results. Annals of Internal Medicine 112: 397-406. 15 Mar 1990

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