Recent Increase in the Incidence of TEM-135 β-Lactamase-harboring Neisseria gonorrhoeae in Korea

BACKGROUND: We investigated the molecular epidemiological characteristics and antimicrobial susceptibility pattern of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates to monitor the change in distribution of bla(TEM) in Korea. METHODS: We collected 804 PPNG isolates from diverse hospitals and clinics mainly located in Seoul, Korea, over a period of 11 years (2005–2015). Isolate susceptibility to seven antimicrobials was determined using the agar dilution test. The molecular epidemiological characteristics of the isolates were determined by Sanger sequencing of bla(TEM), N. gonorrhoeae multiantigen sequence typing (NG-MAST) and plasmid typing. RESULTS: Among 72 fully sequenced PPNG isolates, sixteen (22.2%) possessed TEM-135. All TEM-135 isolates had a common silent mutation (c.18C>T), which was previously unreported. We observed a pattern of continuous increase in the number of TEM-135 isolates since 2012. The median and 90% minimum inhibitory concentration of azithromycin were substantially lower in the TEM-135 group than in the non-PPNG and TEM-1 groups. All TEM-135 isolates showed different NG-MAST types and predominantly harbored Toronto/Rio (75%) plasmids. A comprehensive comparative analysis of PPNG with TEM-135 according to NG-MAST, plasmid type, and year of isolation revealed a wide distribution. CONCLUSIONS: The proportion of TEM-135 PPNG has continuously increased since 2012, in association with clonal spread. The difference at position 18 of the TEM-135 sequence can be interpreted as the existence of multiple clonal complexes. The possibility that TEM-135 was acquired via foreign plasmids requires careful follow-up and continuous monitoring of TEM-135 to ascertain whether it constitutes a step towards evolutionary change.