alone. This is highly suggestive of a synergistic activity in viva. Evaluated on the basis of the mean survival time, a dose of rifampicin 50 mg./kg. administered once a week was shown to be more effective in severe established tuberculosis in mice than the same weekly dose divided over two days (2 x 25 mg./kg.) or five days (5 x 10 mg./kg.). The number of survivors after 80 days of therapy were respectively 26130, 16/30 and 2/30.

A similar experiment with intermittent therapy of established tuberculosis in mice is in progress, taking the clearance of live bacilli in the lungs as a criterion. The first results after 12 weeks of therapy completely confirm that intermittent therapy with a high dose of rifampicin once a week is more effective than the same weekly dose in divided daily portions. The high suitability of rifampicin for intermittent administration in mice raises the hope that rifampicin combined therapy in high dosage once a week may also be successful in man.

Rifampicin in the Treatment of Experimental Tuberculosis in Mice JOHN BA~EN (London)

The full report appears on page 294.

Clinical Results in First Treatment and Retreatment of Advanced Pulmonary Tuberculosis with Rifampicin

PROF. A. GYSELEN and DR. F. SIMON-P• UTHIER (Louvain, Belgium) The value of rifampicin was assessed in original treatment of advanced pulmonary tuberculosis by

comparing the decrease of infectiousness in patients submitted at random to one of the four follow- ing drug regimens: rifampicin (RMP) + placebo (administered for two months), RMP and isoniazid (INH), RMP and ethambutol (EMB), INH and EMB (the last three regimens being administered for four months).

One hundred and twenty patients (30 in each group) with sputum frankly positive on admission were admitted to the study. Six patients had to be excluded for various reasons. The bacteriologic changes were evaluated by weekly cultures until the end of the second month and every two weeks thereafter.

In the RMP-placebo group 18 patients out of 28 showed negative cultures by the end of the second month and after continuing conventional therapy, sputum conversion was achieved in all 28 patients at the 22nd week. In the RMP-INH group, reversal of infectiousness was obtained by the end of the 13th week in 28 out of 29 patients; one patient left the hospital at the 13th week being still positive. In the RMP-EMB and INH-EMB groups the number of patients with negative sputum at the end of the trial period (four months) was 29 out of 30 and 22 out of 27 respectively.

Emergence of bacillary resistance to rifampicin occurred in one patient in the RMP-placebo group; no bacillary resistance to the drugs administered was observed in the other groups.

Tolerance was excellent in all patients, except one in the RMP-EMB group who developed a severe cutaneous hypersensitivity reaction. No liver function disturbances were observed.

In 33 patients with advanced, long-standing and multiresistant pulmonary tuberculosis the bacteriologic changes were evaluated after retreatment with rifampicin alone (group 1: 11 patients) or rifampicin combined to a second active drug (group 2: 22 patients). In most cases the administra- tion of other companion drugs was continued during the trial. However, these drugs were labelled ‘unsuccessful’ since their administration during at least four months, immediately prior to the study, had not resulted in any significant decrease of the number of bacilli in the sputum.

Although 11 patients of group 1 had failed to convert on ethambutol, nine out of them became non-infectious during rifampicin therapy, but in two patients conversion was followed by bacterio- logic relapse. In group 2,21 out of 22 patients converted on rifampicin combined with a second, not previously used, drug; but in one patient conversion was followed by bacteriologic relapse. In five