Экспериментальная комбинация препаратов не сократила сроки лечения туберкулеза
A short-term tuberculosis treatment regimen could improve rates of adherence, reduce rates of adverse events, and lower costs. Fluoroquinolones have shown promising activity against mycobacteria and are established as a critical component of the treatment of multidrug-resistant tuberculosis, with later fluoroquinolones recognized as having a more potent effect. It has been proposed that these drugs may have a role in reducing the duration of tuberculosis treatment.
Moxifloxacin has been approved for a range of indications globally. It has favorable pharmacokinetics, a large volume of distribution, and penetration into epithelial-lining fluid and macrophages. The activity of moxifloxacin in vitro against Mycobacterium tuberculosis, which has been confirmed in murine models and in clinical monotherapy studies, has raised the prospect that the drug could be used as part of an improved regimen. Subsequent studies in mice showed that combination regimens that included moxifloxacin had greater bactericidal activity than standard treatment and could produce cure without relapse after a shorter treatment duration.
When different fluoroquinolones were substituted for ethambutol in a clinical trial, the moxifloxacin-containing regimen produced the most rapid decline in bacterial load and in the proportion of patients with culture negativity at 8 weeks. These findings were confirmed by investigators in Brazil. In contrast, substituting moxifloxacin for isoniazid in an 8-week study resulted in a nonsignificant enhancement in bactericidal effect.
On the basis of supportive evidence from phase 2 studies and the uncertain relationships between 8-week bacteriologic data and the duration of effective therapy, we designed the Rapid Evaluation of Moxifloxacin in Tuberculosis (REMoxTB) study to determine whether the replacement of either isoniazid or ethambutol with moxifloxacin would provide effective tuberculosis treatment in 4 months, as compared with the standard 6-month regimen.