The role of moxifloxacin in tuberculosis therapy

Abstract

Tuberculosis (TB) remains a global threat with more than 9 million new infections. Treatment remains difficult and there has been no change in the duration of the standard regimen since the early 1980s. Moreover, many patients are unable to tolerate this treatment and discontinue therapy, increasing the risk of resistance. There is a growing tide of multidrug resistance and few effective antibiotics to tackle the problem. Since the turn of the millennium there has been a surge in interest in developing new therapies for TB and a number of new drugs have been developed. In this review the repurposing of moxifloxacin, an 8-methoxy-fluoroquinolone, for TB treatment is discussed. The evidence that underpins the development of this agent is reviewed. The results of the recently completed phase III trials are summarised and the reasons for the unexpected outcome are explored. Finally, the design of new trials that incorporate moxifloxacin, and that address both susceptible disease and multidrug resistance, is described.

FIGURE 1

Description of the design of three recent phase III clinical trials incorporating fluoroquinolone antibiotics in treatment-shortening regimens for pulmonary tuberculosis: REMoxTB [9], RIFAQUIN [10] and OFLOTUB [11]. Note that moxifloxacin/rifapentine 900 mg was administered twice weekly and moxifloxacin/rifapentine 1200 mg was administered weekly. H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; M: moxifloxacin; Rp: rifapentine (with a subscript defining dose); G: gatifloxacin; ep, mp, rp and hp: placebos for ethambutol, moxifloxacin, rifampicin and isoniazid, respectively; LJ: Lowenstein–Jensen; MGIT: Mycobacteria Growth Indicator Tube.