A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis

Abstract

Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens.

Keywords: moxifloxacin; pharmacodynamics; pharmacokinetics; tuberculosis.

Figure 1

Two-dimensional imaging of MXF and PZA by MALDI mass spectrometry. Reprinted by permission from Macmillan Publishers Ltd: [Nature medicine] (Prideaux et al 2015), copyright (2015) (a) MALDI mass spectrometry imaging of small molecules in TB-infected lung tissue. The relative ion abundance of specific analytes in regions of interest delineated on the basis of histology staining can be measured to provide semiquantitative data. (b) Ion maps of PZA and MXF in representative (selected from more than 200 lesions) lung lesions sampled throughout the dosing interval; signal intensity is fixed for each drug. Hematoxylin and eosin (H&E) staining of adjacent sections is also shown (bottom). Outlines highlight the necrotic center of each lesion. Scale bars, 5 mm. (c) Left, diffusion of MXF in caseum as a function of caseum cellularity. **P < 0.05, two-tailed unpaired t-test. Error bars, mean ± s.d. (n = 3). Right, a typical H&E example representative of each cellularity score.