Antimicrobial resistance of Mycoplasma genitalium in Korea for two decades

Antimicrobial-resistant (AMR) Mycoplasma genitalium has become a global concern. To assess AMR patterns in Korea, we analyzed the genetic diversity of the AMR-determining sites (ARDS) in M. genitalium across in 285 samples collected over two decades. Mycoplasma-positive samples were collected from various groups: males at one referral center (ORC) from 2014 to 2019 (G1; 43) and from 2020 to 2023 (G2; 54), males at primary care clinics (PCCs) in 2018-2019 (G3; 84), female sex workers at a regional healthcare center in 2004 (G4; 51), and females at PCCs in 2018-2019 (G5; 53). Sanger sequencing was performed at positions 2058/2059 in the 23S rRNA gene and positions GyrA95, GyrA99, ParC83, and ParC87 of topoisomerase IV genes in M. genitalium. In 2004, mutations were rare with S83I (0.0%), M95I (3.4%), and A2059G (10.5%). By 2020-2023, ARDS mutations had become common, peaking at S83I (83.3%) and A2059G (70.4%). No sex differences were observed in ARDS mutations between G3 and G5. A comparison of mutations in males at the ORC showed significant differences in A2059G and S83I between pre-2020 (G1) and post-2020 (G2). Males at the ORC (G1) had higher mutation rates in A2059G, GyrA95, and GyrA99 compared to males at PCCs (G3). Currently, referred males exhibit a rapid increase in AMR, and the synergy between A2059G and S83I/R/N mutations raises concerns regarding the emergence of pan-drug-resistant M. genitalium, potentially leading to an irreversible crisis in treatment options in Korea.