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Rifampicin/Ethambutol/Isoniazid Better Than Rifampicin/Ethambutol For Pulmonary Disease

Combined rifampicin, ethambutol and isoniazid may result in fewer failures or relapses when treating pulmonary disease caused by Mycobacterium avium intracellulare and M xenopi compared with rifampicin plus ethambutol.

However the triple therapy may also be associated with higher overall death rates, researchers say.

These results come from the first randomized trial comparing the use of rifampicin plus ethambutol (RE) and rifampicin, ethambutol and isoniazid (REH) for treatment of pulmonary disease caused by M avium intracellulare, M malmoense and M xenopi.

The trial was conducted by members of the Research Committee of the British Thoracic Society.

From October 1987 to December 1992, human immunodeficiency virus (HIV) negative patients (n=223) with positive mycobacterium cultures, confirmed by the Mycobacterium Reference Laboratories for England, Wales and Scotland, were randomized to either RE or REH for a two year period.

Results showed that there were significantly fewer failures of treatment or relapses of M avium intracellulare with REH compared with RE (16 versus 41 percent, p=0.033). For M xenopi there was a similar, but non-significant trend for REH compared with RE (5 versus 18 percent, p=0.41).

Treatment failures and relapse rates were not significantly different between REH and RE for M malmoense.

When results for the three mycobacteria species were combined, REH had significantly fewer treatment failures or relapses compared with RE (11 versus 22 percent, p=0.033).

Failure of treatment or relapse was not correlated with in vitro resistance tests.

Combined results for all three species showed that there were significantly fewer deaths with RE than with REH (one versus eight percent, p=0.018), although there were no significant differences between RE and REH when the species were taken individually.

The investigators conclude that, "there is a suggestion that REH is associated with higher death rates overall.

"Better regimens are required," they suggest.
Thorax 2001; 56: 167-172. "First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M malmoense, and M xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol"

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