Antituberculosis Activity of Rifampin

Report of Studies Performed and in Progress (1966-1971)

¹ Tuberculosis and Chest Disease Department, University of Naples, Naples, Italy

The results of our experience covering five years and more than 700 cases, may be summarized as follows:

1) Rifampin is an antituberculosis drug whose therapeutic effectiveness is not different from that of isoniazid.

[See pdf for the tables]

2) In the original treatment of pulmonary tuberculosis, the RMP + INH association proved to be significantly more effective than the INH + SM association which had been considered the most powerful two-drug regimen. Moreover, the RMP + INH regimen may result at least as effective as the three-drug regimen INH + SM + EMB which represents at present the best regimen available for original treatment.

3) In the retreatment of chronic cases, where the bacilli are already resistant to the major drugs, RMP associated with EMB gives extremely encouraging results which are definitely better than those currently reported in the literature for any association of minor or second-line drugs.

4) Safety appeared remarkably good.

On the basis of these data and of all the studies performed up to now by ourselves and by other investigators, rifampin seems to have a prominent role in antimycobacterial therapy. It probably can be considered the major improvement in antituberculosis therapy since INH was introduced in the early 1950's.

The high effectiveness, together with the lack of crossresistance between rifampin and the other known antituberculosis drugs, allows new possibilities in the retreatment of cases with multiresistant mycobacteria. Rifampin plus ethambutol would appear the best regimen available for patients in whom ethambutol had not been administered previously. In the other patients, the companion drugs should be carefully chosen from among the second line drugs still active, in view of the rapid selection of resistant mutants occurring under monotherapy.

Regarding original treatment, the high effectiveness of rifampin plus INH regimens, which appeared more active than the other regimens investigated, both in our trials and in those reported in the literature, points to the possibility of a further reduction in the rate of failures and dropouts observed up to now. Moreover, it suggests the possibility of shortening both hospital stay and overall duration of treatment. The follow-up studies in progress will further clarify this problem.

The activity in vitro and in animal experiments on atypical mycobacteria, appears of interest also in view of clinical results of other investigators. This might enable new therapeutic trends in the treatment of infections due to these microorganisms.

Safety of rifampin containing regimens was remarkably good on the basis of both controlled and noncontrolled studies. Problems and contraindications are practically the same as for other drugs, (first trimester of pregnancy, hypersensitivity etc). However, as the kinetics and metabolism of rifampin involve the liver, patients with preexisting impairment of liver function should be treated only under medical supervision and close blood chemistry monitoring. Moreover, in these patients the doses of rifamin should be reduced.