Shorter moxifloxacin-based regimens for drug-sensitive tuberculosis

To the Editor: Gillespie et al. (Oct. 23 issue)1 report that two moxifloxacin-containing regimens for the treatment of tuberculosis were not effective with a shortened treatment period of 4 months. The authors used a moxifloxacin dose of 400 mg per day, which may have contributed to the unfavorable results. Rifampin decreases the average exposure to moxifloxacin (assessed according to the area under the curve [AUC]) by approximately 30%,2 which can be compensated for by an increase in the dose of moxifloxacin.3 In addition, preclinical data combined with pharmacokinetic and pharmacodynamic modeling showed that a higher moxifloxacin dose, of 800 mg per day, is likely to achieve better Mycobacterium tuberculosis microbial killing and suppression of drug resistance.4 Limited data have shown that moxifloxacin at a dose of 800 mg can be given safely.3,5 The inclusion of moxifloxacin drug exposure as a covariate would have been of additional value, considering that the ratio of the AUC to the minimum inhibitory concentration is the driver of moxifloxacin efficacy and that the AUC for moxifloxacin can vary among patients by a factor of 7.6 Such a pharmacokinetic and pharmacodynamic analysis could have shown whether the results of this trial could have been explained by a drug exposure to moxifloxacin that was too low.