Chaisson and colleagues [1] found a good bacteremia-decreasing effect of all dosage schedules used. An early survival advantage was seen with the 500-mg twice-daily dose compared with higher doses. According to the authors, this difference was not a result of more severely ill patients being assigned to receive the higher doses. The authors also contend that the poor survival of patients receiving the 2000-mg twice-daily dose may have been related to the intolerance to clarithromycin of patients assigned to this dose. There was no difference in the number of dose-limiting reactions between patients assigned to the 500-mg and 1000-mg twice-daily dose, and the authors concluded that the survival advantage with the 500-mg twice-daily dose was not fully understood. They recommended use of the 500-mg twice-daily dose in the initial treatment of Mycobacterium avium complex bacteremia.

We wonder, however, if the study results more strongly support a recommendation of the 1000-mg twice-daily dose. The Cox proportional-hazard analysis, with adjustment for baseline Karnofsky performance status, did not show a significant difference (P = 0.54) in the relative risk for death in patients assigned to the 1000-mg twice-daily dose compared with those assigned to the 500-mg dose. Moreover, patients with more than a 1-log decrease in bacteremia were more likely to have improvement in fever and night sweats. This effect was achieved significantly earlier in patients receiving the 1000-mg twice-daily dose than in patients receiving the 500-mg dose. In addition, the median time to a return to a less than 1-log decrease in bacteremia was longer in patients receiving the 1000-mg twice-daily dose.

It therefore seems logical to conclude that the 1000-mg twice-daily dose should be used in the initial treatment of M. avium complex bacteremia rather than the 500-mg dose: The former yields the same relative risk for death, does not differ in dose-limiting reactions, and has greater efficacy.