Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019

Makiko Miura; Katsumi Shigemura; Kayo Osawa; Noriko Nakanishi; Ryohei Nomoto; Reo Onishi; Hiroyuki Yoshida; Toru Sawamura; Shiuh-Bin Fang; Yi-Te Chiang; Shian-Ying Sung; Kuan-Cho Chen; Takayuki Miyara; Masato Fujisawa

doi:10.1099/jmm.0.001533

Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019

J Med Microbiol. 2022 Jun;71(6). doi: 10.1099/jmm.0.001533.

Authors

Makiko Miura^{1

2}, Katsumi Shigemura^{1

3}, Kayo Osawa², Noriko Nakanishi⁴, Ryohei Nomoto⁴, Reo Onishi¹, Hiroyuki Yoshida⁵, Toru Sawamura², Shiuh-Bin Fang^{6

7}, Yi-Te Chiang⁸, Shian-Ying Sung⁹, Kuan-Cho Chen⁸, Takayuki Miyara¹⁰, Masato Fujisawa³

Affiliations

¹ Department of Public Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka Suma-ku, Kobe, 654-0142, Japan.
² Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe, 653-0838, Japan.
³ Department of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
⁴ Department of Infectious Diseases, Kobe Institute of Health, 4-6-5 Minatojima-nakamichi, Chuo-ku, Kobe, 650-0046, Japan.
⁵ Hyogo Clinical Laboratory Corporation, 5-6-2, Aoyamanishi, Himeji, 671-2224 Japan.
⁶ Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, 291 Jhong Jheng Road, Jhong Ho District, New Taipei City, 23561, Taiwan, ROC.
⁷ Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, 250, Wu Hsing Street, Hsin Yi District, Taipei, 11031, Taiwan, ROC.
⁸ Department of Urology, Taipei Medical University Shuang Ho Hospital, 291, Zhongzheng Rd, Zhonghe District, Taipei, 23561, Taiwan, ROC.
⁹ Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing St., Taipei, 110, Taiwan, ROC.
¹⁰ Department of Infection Control and Prevention, Kobe University Hospital, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

PMID: 35700110
DOI: 10.1099/jmm.0.001533

Abstract

Introduction. Azithromycin (AZM) is a therapeutic drug for sexually transmitted infections and is used for Neisseria gonorrhoeae when first- and second-line drugs are not available. Recently, the susceptibility of N. gonorrhoeae against AZM has been decreasing worldwide.Hypothesis/Gap Statement. Azithromycin-resistance (AZM-R) rates among N. gonorrhoeae in Japan are increasing, and the gene mutations and epidemiological characteristics of AZM-R in N. gonorrhoeae have not been fully investigated.Aim. We determined the susceptibility to AZM and its correlation with genetic characteristics of N. gonorrhoeae.Methodology. We investigated the susceptibility to AZM and genetic characteristics of N. gonorrhoeae. Mutations in domain V of the 23S rRNA gene and mtrR were examined in 93 isolates, including 13 AZM-R isolates. Spread and clonality were examined using sequence types (STs) of multi-antigen sequence typing for N. gonorrhoeae (NG-MAST), and whole genome analysis (WGA) to identify single nucleotide polymorphisms.Results. The number of AZM-R isolates increased gradually from 2015 to 2019 in Hyogo (P=0.008). C2599T mutations in 23S rRNA significantly increased in AZM-R isolates (P<0.001). NG-MAST ST4207 and ST6762 were frequently detected in AZM-R isolates, and they had higher MICs to AZM from 6 to 24 µg/ml. The phylogenic tree-based WGA showed that all isolates with ST4207 were contained in the same clade, and isolates with ST6762 were divided into two clades, AZM-S isolates and AZM-R isolates, which were different from the cluster containing ST1407.Conclusion. Our study showed yearly increases in AZM-R rates in N. gonorrhoeae. NG-MAST ST4207 and ST6762 were not detected in our previous study in 2015 and were frequently identified in isolates with higher MICs to AZM. WGA confirmed that isolates with these STs are closely related to each other. Continued surveillance is needed to detect the emergence and confirm the spread of NG-MAST ST4207 and ST6762.

Keywords: 23S rRNA; NG-MAST; Neisseria gonorrhoeae; WGA; azithromycin resistance; mtrR.

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Azithromycin / pharmacology
Azithromycin / therapeutic use
Drug Resistance, Bacterial / genetics
Gonorrhea* / drug therapy
Gonorrhea* / epidemiology
Humans
Japan / epidemiology
Microbial Sensitivity Tests
Neisseria gonorrhoeae* / genetics
RNA, Ribosomal, 23S / genetics

Substances

Anti-Bacterial Agents
RNA, Ribosomal, 23S
Azithromycin