lunes, 19 de marzo de 2018

Cephalosporin-Resistant Neisseria gonorrhoeae Clone, China - Volume 24, Number 4—April 2018 - Emerging Infectious Disease journal - CDC

Cephalosporin-Resistant Neisseria gonorrhoeae Clone, China - Volume 24, Number 4—April 2018 - Emerging Infectious Disease journal - CDC

Volume 24, Number 4—April 2018

Research Letter

Cephalosporin-Resistant Neisseria gonorrhoeae Clone, China

Shao-Chun Chen, Yue-Ping YinComments to Author , and Xiang-Sheng Chen
Author affiliations: Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China (S.-C. Chen, Y.-P. Yin, X.-S. Chen)Chinese Center for Disease Control and Prevention, Nanjing (S.-C. Chen, Y.-P. Yin, X.-S. Chen)


Cephalosporin-resistant Neisseria gonorrhoeae is a major public health concern. N. gonorrhoeae of multiantigen sequence type G1407 and multilocus sequence type 1901 is an internationally spreading cephalosporin-resistant clone. We detected 4 cases of infection with this clone in China and analyzed resistance determinants by using N. gonorrhoeae sequence typing for antimicrobial resistance.
Gonorrhea, the second most prevalent sexually transmitted infection (STI) globally, remains a major public health concern in China. From 2015 to 2016, the reported cases of gonorrhea in China increased by 14.7% (100,245 to 115,024) (1). The extended-spectrum cephalosporin ceftriaxone has been recommended as monotherapy to treat gonorrhea in China since 2007 (2), but resistance to this drug emerged almost at the same time (3). Presently, the transmission of internationally spread cephalosporin-resistant clones in China has become a threat to effectively controlling gonorrhea (4). Strains with N. gonorrhoeae multiantigen sequence type (NG-MAST) G1407 and multilocus sequence type (MLST) 1901 have been successful clones associated with cephalosporin resistance and have caused clinical treatment failures in France and Spain (5,6); these strains have also became the predominant clones in the United Kingdom (7) and Japan (8) and among US men who have sex with men (9). Here we report 4 cephalosporin-resistant NG-MAST G1407/MLST 1901 clones identified out of 2,038 isolates collected through China’s Gonococcal Resistance Surveillance Program during 2015–2016.
Demographic and clinical information for the 4 case-patients are summarized in Technical AppendixTable 1. All case-patients were adult men; gonococcal isolates were obtained from urethral swab samples. The 4 men had obvious urethral discharge and were diagnosed with acute urethritis. Gram staining and culture of the urethral swabs were positive for gonococcal infection. One of the 4 patients self-reported being a man who has sex with men. One of the infections, occurring in Zhejiang Province, was treated with a single-dose regimen of spectinomycin (4 g); the other 3 infections, occurring in the municipality of Chongqing, were treated with a 2-dose regimen of ceftriaxone (1 g) administered over 2 days. Test-of-cure follow-ups were not performed.
All strains were transferred to the reference laboratory at the National Center for Sexually Transmitted Disease Control, Chinese Center for Disease Control and Prevention. Gram staining, a rapid oxidase reaction test, and a carbohydrate utilization test confirmed the identification of N. gonorrhoeae. We determined antimicrobial susceptibility to ceftriaxone (CRO), cefixime (CFM), spectinomycin (SPT), azithromycin (AZM), ciprofloxacin (CIP), and penicillin (PEN) by using the agar dilution method. We detected β-lactamase (penicillinase)–producing N. gonorrhoeae isolates by using a nitrocefin solution filter paper test. These strains were resistant to CRO, CFM, PEN, and CIP but susceptible to AZM and SPT based on susceptibility and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing ( (Table). MICs of ceftriaxone ranged from 0.25 to 0.50 mg/L, and MICs of cefixime ranged from 0.5 to 1.0 mg/L.
We performed NG-MAST and MLST genotyping to identify the sequence types (10). MLST showed all 4 strains to be type 1901, and NG-MAST showed the Zhejiang strain to be sequence type (ST) 10332 and the Chongqing strains to be ST1407. ST10332 has a 2-basepair difference in the porB (porB6067) gene from that of ST1407 (porB908) and belongs to genogroup G1407. We used N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) to identify the characteristics of resistance determinants (11). NG-STAR showed 2 of the Chongqing strains to be ST90; the third Chongqing strain was ST194. The strain isolated in Zhejiang was ST507. All 4 strains had type XXXIV mosaic penA (penA 34.001), −35A Del in the mtrR promoter (mtrR1), G120K-A121N/D in PorB (PorB8/11), L421P in PonA (PonA1), S91F-D95A/G in GyrA (GyrA1/7), S87R in ParC (ParC3), and wild-type 23srRNA (23 srRNA0) (Technical Appendix Table 2).
We conclude that the internationally reported cephalosporin-resistant NG-MAST G1407/MLST 1901 N. gonorrhoeae clone has spread into China. Genotyping and resistance determinants analysis showed similarity to the predominant G1407/MLST 1901 clone reported in other regions (79), indicating that importation into and transmission within China has occurred. Our findings suggest that increased monitoring of this clone by China’s Gonococcal Resistance Surveillance Program will be vital for monitoring trends in antimicrobial resistance.
Dr. S.-C. Chen received his PhD in microbiology and 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.


We are grateful to the members of China’s Gonococcal Resistance Surveillance Program for providing the isolates and making this study possible. We thank William Shafer for his valuable comments.
The study was supported by grants from the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021) and the Jiangsu Natural Science Foundation (BK20171133).


  1. Chinese Center for Disease Control and Prevention. Epidemic of infectious diseases in China, 2016 [2018 Jan 12].
  2. Wang QQZhang GC. Guidelines for diagnosis and treatment of sexually transmitted diseases [in Chinese]. Shanghai: Shanghai Science and Technology Press; 2007.
  3. Chen SCYin YPDai XQUnemo MChen XSAntimicrobial resistance, genetic resistance determinants for ceftriaxone and molecular epidemiology of Neisseria gonorrhoeae isolates in Nanjing, China. J Antimicrob Chemother2014;69:295965DOIPubMed
  4. Chen SCYin YPDai XQUnemo MChen XSFirst nationwide study regarding ceftriaxone resistance and molecular epidemiology of Neisseria gonorrhoeae in China. J Antimicrob Chemother2016;71:929DOIPubMed
  5. Unemo MGolparian DNicholas ROhnishi MGallay ASednaoui PHigh-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother2012;56:127380DOIPubMed
  6. Cámara JSerra JAyats JBastida TCarnicer-Pont DAndreu Aet al. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother2012;67:185860DOIPubMed
  7. Ison CATown KObi CChisholm SHughes GLivermore DMet al.GRASP collaborative groupDecreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis2013;13:7628DOIPubMed
  8. Shimuta KWatanabe YNakayama SMorita-Ishihara TKuroki TUnemo Met al. Emergence and evolution of internationally disseminated cephalosporin-resistant Neisseria gonorrhoeaeclones from 1995 to 2005 in Japan. BMC Infect Dis2015;15:378DOIPubMed
  9. Grad YHKirkcaldy RDTrees DDordel JHarris SRGoldstein Eet al. Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect Dis2014;14:2206DOIPubMed
  10. Martin IMIson CAAanensen DMFenton KASpratt BGRapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis2004;189:1497505DOIPubMed
  11. 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


Technical Appendix

Cite This Article

DOI: 10.3201/eid2404.171817

No hay comentarios:

Publicar un comentario