Limited macrolide and fluoroquinolone resistance data are available in France for . We performed a multicentre cross-sectional study to investigate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in -positive patients in metropolitan France between 2018 and 2020 and in overseas France in 2018 and 2019. Each year, a 1-month prospective collection of -positive specimens was proposed to metropolitan French microbiology diagnostic laboratories, and a similar 3-month collection was proposed to overseas French laboratories. Resistance-associated mutations were detected using commercial kits and sequencing. A total of 1630 . -positive specimens were analysed. In metropolitan France, the prevalence of macrolide resistance-associated mutations ranged between 34.7% (95% CI 29.4% to 40.4%) and 42.9% (95% CI 37.1% to 49.0%) between 2018 and 2020 and was significantly higher in men (95% CI 52.4% to 60.2%) than in women (95% CI 15.9% to 22.2%) (p<0.001). These prevalences were significantly higher than those of 6.1% (95% CI 3.7% to 10.3%) and 14.7% (95% CI 10.9% to 19.6%) observed in overseas France in 2018 and 2019 (p<0.001), where no difference between genders was noted. The prevalence of fluoroquinolone resistance-associated mutations was also significantly higher in metropolitan France (14.9% (95% CI 11.2% to 19.5%) to 16.1% (95% CI 12.1% to 21.2%)) than in overseas France (1.3% (95% CI 0.4% to 3.7%) and 2.6% (95% CI 1.3% to 5.3%) in 2018 and 2019, respectively) (p<0.001), with no difference between men and women regardless of the location. This study reports the high prevalence of macrolide and fluoroquinolone resistance-associated mutations in in metropolitan France and highlights the contrast with low prevalence in overseas France. In metropolitan France, macrolide resistance-associated mutation prevalence was three times higher in men than in women, which was likely to be driven by the proportion of men who have sex with men. This suggests that gender and sexual practice should also be taken into account for the management of infections.Read less <