Abstract: We identified five RCTs (1330 participants) that met the inclusion criteria. None of the included trials examined regimens of less than six months duration. Fluoroquinolones added to standard regimens A single trial (174 participants) added levofloxacin to the standard first-line regimen. Relapse and treatment failure were not reported. For death, sputum conversion, and adverse events we are uncertain if there is an effect (one trial, 174 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for ethambutol in standard regimens Three trials (723 participants) substituted ethambutol with moxifloxacin, gatifloxacin, and ofloxacin into the standard first-line regimen. For relapse, we are uncertain if there is an effect (one trial, 170 participants, very low quality evidence). No trials reported on treatment failure. For death, sputum culture conversion at eight weeks, or serious adverse events we do not know if there was an effect (three trials, 723 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for isoniazid in standard regimens A single trial (433 participants) substituted moxifloxacin for isoniazid. Treatment failure and relapse were not reported. For death, sputum culture conversion, or serious adverse events the substitution may have little or no difference (one trial, 433 participants, low quality evidence for all three outcomes). Fluoroquinolines in four month regimens Six trials are currently in progress testing shorter regimens with fluoroquinolones. Ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin have been tested in RCTs of standard first-line regimens based on rifampicin and pyrazinamide for treating drug-sensitive TB. There is insufficient evidence to be clear whether addition or substitution of fluoroquinolones for ethambutol or isoniazid in the first-line regimen reduces death or relapse, or increases culture conversion at eight weeks. Much larger trials with fluoroquinolones in short course regimens of four months are currently in progress.

Plain-language summary: We examined the research published up to 6 March 2013 and we identified five randomised controlled trials (1330 people) that met the inclusion criteria. The trials were performed in low- and middle-income countries located in geographically diverse areas but there was a lack of studies conducted in Asia. We found no studies that examined the effect of including fluoroquinolones in a standard six month TB treatment regimen on treatment failure. We do not know whether adding fluoroquinolones or substituting fluoroquinolones for ethambutol in a standard six month TB treatment regimen reduces treatment failure, relapse, death, or adverse events. Substituting fluoroquinolones for isoniazid in a standard six month TB treatment regimen may have little or no difference upon death and adverse events. Currently, there are nine randomised controlled trials ongoing. HIV-positive participants were relatively well-represented in the included trials but none of the included trials stratified outcomes by HIV status. Also, the primary outcomes of all the included trials were reached before initiation of antiretroviral treatment. Evidence is generally lacking on the safety and efficacy of fluoroquinolone additions or substitutions in children (< 18 years) and in pregnant and lactating women.