Shortening Tuberculosis Treatment with Fluoroquinolones: Lost in Translation?

Abstract

The disappointing recent failure of fluoroquinolone-containing regimens to shorten the duration of tuberculosis treatment in costly phase 3 trials has raised serious questions about the reliability of preclinical tuberculosis models, especially mice, and the current paradigm of regimen development. Therefore we re-examined data from murine models and early-stage clinical trials on which the pivotal trials were based, concluding that phase 3 trial results were in line with preceding studies. Finally, we offer suggestions for a more efficient and integrated preclinical and clinical regimen development program where quantitative pharmacokinetic and pharmacodynamic models more predictive of curative treatment durations are set forth.