Friday, March 29, 2019

Ahead of Print - Identification of Internationally Disseminated Ceftriaxone-Resistant Neisseria gonorrhoeae Strain FC428, China - Volume 25, Number 7—July 2019 - Emerging Infectious Diseases journal - CDC

Ahead of Print - Identification of Internationally Disseminated Ceftriaxone-Resistant <em>Neisseria gonorrhoeae</em> Strain FC428, China - Volume 25, Number 7—July 2019 - Emerging Infectious Diseases journal - CDC

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Volume 25, Number 7—July 2019

Research Letter

Identification of Internationally Disseminated Ceftriaxone-Resistant Neisseria gonorrhoeae Strain FC428, China

Shao-Chun Chen, Yan Han, Liu-Feng Yuan, Xiao-Yu Zhu, and Yue-Ping YinComments to Author 
Author affiliations: Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China (S.-C. Chen, Y. Han, X.-Y. Zhu, Y.-P. Yin)Chinese Center for Disease Control and Prevention, Nanjing (S.-C. Chen, Y. Han, X-.Y. Zhu, Y.-P. Yin)Beijing Ditan Hospital Capital Medical University, Beijing, China (L.-F. Yuan)

Abstract

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.
Ceftriaxone has been used to treat gonorrhea in China and most other countries for >1 decade, but the level of decreased susceptibility or clinical resistance to ceftriaxone has increased (1). Moreover, the international spread of ceftriaxone-resistant clones has been recognized as a threat to effective control of gonorrhea (2). We describe an imported ceftriaxone-resistant N. gonorrhoeae strain isolated in China in 2016.
The patient was a heterosexual man in his late twenties. He reported unprotected 1-night heterosexual sex in Beijing in July 2016. Urethral discharge with dysuria occurred 3 days after the sexual activity. He was prescribed oral cephalosporin when he visited a private clinic in July. Because the urethral discharge did not resolve, he visited the sexually transmitted diseases clinic in Beijing Ditan Hospital (Beijing, China) in August.
Laboratory analysis of a urethral swab sample found gram-negative diplococci within leukocytes. Culture and nucleic acid amplification test were positive for N. gonorrhoeae. Screening for other sexually transmitted infections by nucleic acid amplification test was negative for Chlamydia trachomatisUreaplasma urealyticum, and Mycoplasma hominis.
The patient was treated with a 1-g intravenous dose of ceftriaxone once per day for 3 days. His symptoms improved after 3 days, and a test-of-cure by culture showed the treatment was successful. A telephone follow-up after 1 month indicated a lack of urethral discharge, and the patient provided information that his female sexual partner worked in a nightclub and had sexual contact with men from foreign countries.
The bacterial isolate was transferred to the reference laboratory at the National Center for Sexually Transmitted Disease Control, Chinese Center for Disease Control and Prevention (Nanjing, China). Gram staining and a carbohydrate utilization test confirmed N. gonorrhoeae. We confirmed antimicrobial susceptibilities to ceftriaxone, cefixime, spectinomycin, azithromycin, ciprofloxacin, and tetracycline for this isolate by using the agar dilution method. The strain was resistant to ceftriaxone (MIC 0.5 mg/L), cefixime (MIC 1 mg/L), tetracycline (4 mg/L), and ciprofloxacin (>32 mg/L) and susceptible to azithromycin (MIC 0.25 mg/L) and spectinomycin (MIC 16 mg/L) in accordance with the European Committee on Antimicrobial Susceptibility Testing protocol (http://www.eucast.org/clinical_breakpoints).
We performed N. gonorrhoeae multiantigen sequence typing (NG-MAST) (3) and multilocus sequence typing (MLST) (4) to identify the sequence types (STs). The MLST type was ST1903, and NG-MAST type was ST3435. We used N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) (5) to identify the characteristics of resistance determinants. The NG-STAR type was ST233, which contains a type 60 mosaic penA allele (penA 60.001), −35A Del in the mtrR promoter (mtrR1), G120K-A121D in PorB (PorB8), L421P in PonA (PonA1), S91F-D95A in GyrA (GyrA7), S87R in ParC (ParC3), and wild-type 23srRNA (23 srRNA0).
The genotype (MLST1903/NG-MAST3435/NG-STAR233) of this isolate was identical to the 2 ceftriaxone-resistant N. gonorrhoeae FC428 and FC460 isolated in 2015 in Japan (6) and similar to other resistant strains isolated in 2017 in Denmark (7), Canada (8), and Australia (9) (Table). Type 60 mosaic PenA (penA 60.001), which contained A311V and T483S alterations, were the key ceftriaxone resistance mutations and typical of this internationally disseminated resistant clone.
The timeline and epidemiologic data of all previous reports of the infections suggest this clone originated in Japan in 2015 and was disseminated to China, Denmark, Canada, and Australia afterwards. Moreover, this resistant clone may have a fitness advantage over previously reported “superbug” H041 and has successfully spread worldwide (9). Accordingly, enhancing international collaborative surveillance on the ceftriaxone-resistant clone is crucial.
In conclusion, we identified a ceftriaxone-resistant N. gonorrhoeae strain that has sustainably transmitted in several countries for ≈3 years. These findings indicate an imported risk and a further transmission of resistant clones in China and demonstrate the need for enhanced local and global gonococcal antimicrobial surveillance to track the emergence and dissemination of resistant strains for timely control of spread (10).
Dr. Chen is an associate professor at the National Center for STD Control, Chinese Center for Disease Control and Prevention. His primary research interests include molecular epidemiology and the antimicrobial resistance mechanism of N. gonorrhoeae.
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Acknowledgments

We are grateful to Beijing Ditan Hospital, a member of China’s Gonococcal Resistance Surveillance Program, for providing the isolate and making the study possible. We thank William Shafer for his valuable comments.
This study was supported by a grant from the Chinese Academy Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021) and the Jiangsu Natural Science Foundation (BK20171133).
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References

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  2. Chen  SCYin  YPChen  XSCephalosporin-resistant Neisseria gonorrhoeae clone, China. Emerg Infect Dis2018;24:8046DOIPubMed
  3. Martin  IMIson  CAAanensen  DMFenton  KASpratt  BGRapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis2004;189:1497505DOIPubMed
  4. Jolley  KAMaiden  MCBIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics2010;11:595DOIPubMed
  5. Demczuk  WSidhu  SUnemo  MWhiley  DMAllen  VGDillon  JRet al. Neisseria gonorrhoeae sequence typing for antimicrobial resistance, a novel antimicrobial resistance multilocus typing scheme for tracking global dissemination of N. gonorrhoeae strains. J Clin Microbiol2017;55:145468DOIPubMed
  6. Nakayama  SShimuta  KFurubayashi  KKawahata  TUnemo  MOhnishi  MNew ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain with a novel mosaic penA gene isolated in Japan. Antimicrob Agents Chemother2016;60:433941DOIPubMed
  7. Terkelsen  DTolstrup  JJohnsen  CHLund  OLarsen  HKWorning  Pet al. Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017. Euro Surveill2017;22:22DOIPubMed
  8. Lefebvre  BMartin  IDemczuk  WDeshaies  LMichaud  SLabbé  ACet al. Ceftriaxone-Resistant Neisseria gonorrhoeae, Canada, 2017. Emerg Infect Dis2018;24:3813DOIPubMed
  9. Lahra  MMMartin  IDemczuk  WJennison  AVLee  KINakayama  SIet al. Cooperative recognition of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain. Emerg Infect Dis2018;24:73540DOIPubMed
  10. Wi  TLahra  MMNdowa  FBala  MDillon  JRRamon-Pardo  Pet al. Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action.PLoS Med2017;14:e1002344DOIPubMed
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Table

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Suggested citation for this article: Chen SC, Han Y, Yuan LF, Zhu XY, Yin YP. Identification of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, China. Emerg Infect Dis. 2019 Jul [date cited]. https://doi.org/10.3201/eid2507.190172
DOI: 10.3201/eid2507.190172


Original Publication Date: 3/22/2019

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