title: 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.
authors.affiliation: Department of Medicine, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland INSERM U1088, Amiens, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lanoix
authors.affiliation: Department of Medicine, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.affiliation: Department of Medicine, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Nuermberger
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D017211:Treatment Failure; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones
keywords: OFLOTUB; REMox-TB; fluoroquinolones; shortening regimen; tuberculosis