Moxifloxacin Outperforms Azithromycin for M genitalium

Moxifloxacin was superior to azithromycin for treating Mycoplasma genitalium (MG) infection when resistance testing was unavailable, according to results from the FARTHEST randomized clinical trial published in Clinical Infectious Diseases.

The study evaluated treatment of MG infection, which the authors said is increasingly characterized by high rates of macrolide and fluoroquinolone resistance. Although international guidelines recommend resistance-guided therapy, the authors noted that access to genotypic testing is limited and randomized trial evidence has been lacking.

FARTHEST was a monocentric, open-label, superiority randomized controlled trial that enrolled adults with MG infection detected by multiplex polymerase chain reaction (PCR). Participants were randomized 1:1 to receive moxifloxacin 400mg daily for 10 days or azithromycin 500mg daily for 6 days. A test of cure was performed at least 28 days after treatment completion. The primary endpoint was microbiological cure in the intention-to-treat (ITT) and per-protocol (PP) populations.

Among 358 randomized participants, microbiological cure in the ITT analysis was achieved by 87.0% of participants treated with moxifloxacin and 61.2% of those treated with azithromycin. The absolute risk difference was 25.8 percentage points, with a 95% confidence interval of 16.5 to 35.2 percentage points. The superiority of moxifloxacin was confirmed in both the ITT and PP analyses.

Moxifloxacin remained superior across most subgroups, while azithromycin showed comparable efficacy only among heterosexual individuals. Doxycycline coadministration did not improve outcomes. Both regimens were well tolerated, with only 1 discontinuation reported. The authors concluded that moxifloxacin demonstrated superior efficacy compared with azithromycin in the absence of resistance testing and said the randomized data support its use as a first-line option when resistance assays are unavailable.

Source: Rossotti R, Baiguera C, Bernasconi DP, et al. A randomized clinical trial to compare moxifloxacin versus azithromycin for the treatment of Mycoplasma genitalium: the FARTHEST study. Clin Infect Dis. Published online 17 May 2026. doi:10.1093/cid/ciag317