Ann Lab Med.  2018 Jul;38(4):324-330. 10.3343/alm.2018.38.4.324.

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

Affiliations
  • 1Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea. hmlee.labmed@gmail.com
  • 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
  • 3Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, Korea.
  • 4Department of Laboratory Medicine, The National Police Hospital, Seoul, Korea.

Abstract

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.

Keyword

Penicillinase-producing Neisseria gonorrhoeae; blaTEM; TEM-135 β-lactamase; NG-MAST; Plasmid typing; Antibiotic resistance; Korea

MeSH Terms

Agar
Azithromycin
Drug Resistance, Microbial
Follow-Up Studies
Incidence*
Korea*
Microbial Sensitivity Tests
Neisseria gonorrhoeae*
Neisseria*
Plasmids
Seoul
Silent Mutation
Agar
Azithromycin

Figure

  • Fig. 1 Chronological changes in the percentage of isolates with TEM-1 or TEM-135 β-lactamase among all the N. gonorrhoeae isolates collected between 2005 and 2015.

  • Fig. 2 Genetic distance tree and plasmid types of penicillinase-producing Neisseria gonorrhoeae with TEM-1 or TEM-135 grouped according to porB genotype. Alleles marked with a black circle or numbers shown in red are associated with isolates harboring TEM-135; numbers in parenthesis indicate the number of isolates with the same sequence type. Although sequence types are diverse among isolates with TEM-135, two small clusters (cluster A and B) accounting for 56.3% (9/16) of all TEM-135 isolates appear to be independently segregated. Abbreviation: NG-MAST, Neisseria gonorrhoeae multiantigen sequence typing; ST, sequence type; AF, African; AS, Asian; TR, Tronto/Rio.


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