Global macrolide non-susceptibility in urogenital Ureaplasma and Mycoplasma: a systematic review and meta-analysis

Rising macrolide resistance and elevated minimum inhibitory concentrations (MICs) among urogenital Mycoplasma and Ureaplasma species threaten effective treatment. Continuous surveillance is essential to guide clinical practice and mitigate the spread of antimicrobial resistance. To estimate the pooled prevalence across included studies of erythromycin resistance and elevated MICs to other macrolides—including azithromycin, clarithromycin, roxithromycin, and josamycin—in urogenital Ureaplasma spp. and Mycoplasma isolates. A systematic review and meta-analysis of studies published up to 8 February, 2026, was conducted using R software. The pooled prevalence across included studies of erythromycin non-susceptibility was 13.3% (95% CI: 7.8–21.8) among Ureaplasma spp. and 75.7% (95% CI: 57.0–88.0) among Mycoplasma spp. Elevated non-susceptibility was also observed for other macrolides in Ureaplasma spp., including roxithromycin (15.3%; 95% CI: 8.3–26.7), clarithromycin (9.9%; 95% CI: 4.8–19.2), azithromycin (6.4%; 95% CI: 3.4–11.6), and josamycin (2.6%; 95% CI: 1.2–5.5). In contrast, the corresponding pooled estimates in Mycoplasma spp. were substantially higher for roxithromycin (63.4%; 95% CI: 28.6–88.2), clarithromycin (84.5%; 95% CI: 66.3–93.8), azithromycin (78.8%; 95% CI: 70.2–85.5), and josamycin (7.7%; 95% CI: 3.7–15.3). Because M. hominis is intrinsically resistant to 14- and 15-membered macrolides, pooled estimates for this species should be interpreted cautiously and are most clinically relevant for josamycin, for which the pooled prevalence across included studies of non-susceptibility was 6.1% (95% CI: 2.3–14.8). Significant geographic variation was observed for erythromycin, clarithromycin, azithromycin, and josamycin (all P < 0.05), whereas no significant geographic difference was detected for roxithromycin ( P = 0.283). No significant temporal trends were observed for any of the evaluated macrolides, including erythromycin ( P = 0.994), roxithromycin ( P = 0.165), clarithromycin ( P = 0.615), azithromycin ( P = 0.326), or josamycin ( P = 0.467). Given the high resistance to erythromycin and the moderate elevation of azithromycin MICs, cautious use of these agents is warranted. In contrast, josamycin demonstrates consistently low MICs—particularly against M. hominis —and may represent a promising alternative. Ongoing global surveillance remains essential to support evidence-based treatment guidelines.