© 2005 American Thoracic Society
The Role of Four Months of Rifampicin in the Treatment of Latent Tuberculosis InfectionTo the Editor:The way that the United States chooses to prevent tuberculosis has always been a subject of interest to the rest of the world. Its decision in the 1950s not to use Bacille Calmette-Guérin (BCG) in the light of conflicting trial evidence was a brave one. It must have been particularly hard on the Chicago infants or the North American Indians for whom BCG had been shown to have a protective effect (1, 2). The decision not to use BCG has also been shown to be questionable in the light of protection against infection with MDR-TB (3). Credit, however, must be given to the United States for inventing the concept of preventive therapy for latent tuberculosis infection; the initial trials of up to a year of isoniazid alone were appropriate when therapy lasted for 2 years and cost limitation was all important. With the reduction of treatment for active disease to six months, giving treatment for latent infection for longer is no longer appropriate. Meta-analysis has shown there is no additional benefit of giving isoniazid for any longer than 6 months (4), only increased toxicity, and these data have the highest category of evidence level (SIGN 1++) (5). The enormous reduction in costs of rifampicin has made a rifampicin-containing preventive regimen very attractive. However, the United States' venture into 2 months rifampicin and pyrazinamide has proved a disaster owing to serious adverse effects. Men and indeed women are not mice (6). The advocacy of the 4-month regimen of rifampicin only by Reichman and coworkers must be seriously questioned (7). First, there is the danger of creating rifampicin resistance, which is much harder to treat than isoniazid resistance. The lack of evidence for isoniazid prophylaxis leading to isoniazid resistance as a reason for using rifampicin alone, as suggested by Reichman and coworkers, may be dangerous. Absence of proof (of a single drug prophylaxis resulting in resistance to that drug) is not proof of absence. What has been demonstrated, or rather not demonstrated, in a well conducted trial may not pertain in the hustle and bustle of the service setting where active disease could be missed and a single drug given in error. Second, there has only been one trial of the use of rifampicin alone for latent TB infection, and that with a 3-month regimen (8). "Inferential reasoning" to suggest that 4 months of rifampicin be used is not good enough (SIGN level 4), when absolutely no randomized controlled clinical trial evidence is available. We have enough problems managing patients with rifampicin-resistant disease, created by the medical services, without artificially and unnecessarily providing another potential avenue for its increase. Why is the United States so reluctant to consider the combination of rifampicin and isoniazid for 3 months, which was shown to be as effective as rifampicin alone in the same trial (8), has SIGN level 1+ evidence from trials and 2+ from clinical studies, and has been used extensively in the UK for nearly 20 years, with no reports of serious adverse outcomes (9)?
a Cardiothoracic Centre, Liverpool, United Kingdom FOOTNOTES Conflict of Interest Statement: P.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; P.O. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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