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Volume 26, Number 3—March 2020

Genomic and Phenotypic Variability in Neisseria gonorrhoeae Antimicrobial Susceptibility, England

Katy TownComments to Author , Simon Harris, Leonor Sánchez-Busó, Michelle J. Cole, Rachel Pitt, Helen Fifer, Hamish Mohammed, Nigel Field, and Gwenda Hughes
Author affiliations: National Institute for Health Research, London, UK (K. Town, G. Hughes); Public Health England, London (K. Town, M.J. Cole, R. Pitt, H. Fifer, H. Mohammed, G. Hughes); University College London, London (K. Town, N. Field, G. Hughes); Microbiotica Ltd, Cambridge, UK (S. Harris); Wellcome Sanger Institute, Cambridge (S. Harris, L. Sánchez-Busó); University of Oxford, Oxford, UK (L. Sánchez-Busó)

Main Article

Figure 2

Phylogenetic tree of Neisseria gonorrhoeae isolates from England and other countries in Europe in a study of antimicrobial susceptibility, 2013–2016, including metadata for study type, MICs for ceftriaxone and cefixime, and presence of penA-34 alleles. We sequenced 1,277 isolates; 948 isolates were from other countries in Europe. The penA-34 clades from Europe are labeled M1 and M2, as noted by Harris, et al. (5).

Figure 2. Phylogenetic tree of Neisseria gonorrhoeae isolates from England and other countries in Europe in a study of antimicrobial susceptibility, 2013–2016, including metadata for study type, MICs for ceftriaxone and cefixime, and presence of penA-34 alleles. We sequenced 1,277 isolates; 948 isolates were from other countries in Europe. The penA-34 clades from Europe are labeled M1 and M2, as noted by Harris et al. (5).

Main Article

  1. Tapsall  JW. Antimicrobial resistance in Neisseria gonorrhoeae. Geneva: World Health Organization; 2001.
  2. Wi  T, Lahra  MM, Ndowa  F, Bala  M, Dillon  JR, Ramon-Pardo  P, et al. Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action. PLoS Med. 2017;14:e1002344. DOIPubMedGoogle Scholar
  3. Demczuk  W, Lynch  T, Martin  I, Van Domselaar  G, Graham  M, Bharat  A, et al. Whole-genome phylogenomic heterogeneity of Neisseria gonorrhoeae isolates with decreased cephalosporin susceptibility collected in Canada between 1989 and 2013. J Clin Microbiol. 2015;53:191200. DOIPubMedGoogle Scholar
  4. Grad  YH, Harris  SR, Kirkcaldy  RD, Green  AG, Marks  DS, Bentley  SD, et al. Genomic epidemiology of gonococcal resistance to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in the United States, 2000–2013. J Infect Dis. 2016;214:157987. DOIPubMedGoogle Scholar
  5. Harris  SR, Cole  MJ, Spiteri  G, Sánchez-Busó  L, Golparian  D, Jacobsson  S, et al.; Euro-GASP study group. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. Lancet Infect Dis. 2018;18:75868. DOIPubMedGoogle Scholar
  6. Town  K, Obi  C, Quaye  N, Chisholm  S, Hughes  G; GRASP Collaborative Group. Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales. Sex Transm Infect. 2017;93:3945. DOIPubMedGoogle Scholar
  7. Kirkcaldy  RD, Zaidi  A, Hook  EW III, Holmes  KK, Soge  O, del Rio  C, et al. Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010. Ann Intern Med. 2013;158:3218. DOIPubMedGoogle Scholar
  8. Allan-Blitz  L-T, Humphries  RM, Hemarajata  P, Bhatti  A, Pandori  MW, Siedner  MJ, et al. Implementation of a rapid genotypic assay to promote targeted ciprofloxacin therapy of Neisseria gonorrhoeae in a large health system. Clin Infect Dis. 2017;64:126870.PubMedGoogle Scholar
  9. Grad  YH, Kirkcaldy  RD, Trees  D, Dordel  J, Harris  SR, Goldstein  E, et al. Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect Dis. 2014;14:2206. DOIPubMedGoogle Scholar
  10. Town  K, Bolt  H, Croxford  S, Cole  M, Harris  S, Field  N, et al. Neisseria gonorrhoeae molecular typing for understanding sexual networks and antimicrobial resistance transmission: A systematic review. J Infect. 2018;76:50714. DOIPubMedGoogle Scholar
  11. Fifer  H, Cole  M, Hughes  G, Padfield  S, Smolarchuk  C, Woodford  N, et al. Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study. Lancet Infect Dis. 2018;18:57381. DOIPubMedGoogle Scholar
  12. Eyre  DW, Town  K, Street  T, Barker  L, Sanderson  N, Cole  MJ, et al. Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018. Euro Surveil. 2019;24.
  13. De Silva  D, Peters  J, Cole  K, Cole  MJ, Cresswell  F, Dean  G, et al. Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study. Lancet Infect Dis. 2016;16:1295303. DOIPubMedGoogle Scholar
  14. Hughes  G, Nichols  T, Ison  CA. Estimating the prevalence of gonococcal resistance to antimicrobials in England and Wales. Sex Transm Infect. 2011;87:52631. DOIPubMedGoogle Scholar
  15. Mohammed  H, Ison  CA, Obi  C, Chisholm  S, Cole  M, Quaye  N, et al.; GRASP Collaborative Group. Frequency and correlates of culture-positive infection with Neisseria gonorrhoeae in England: a review of sentinel surveillance data. Sex Transm Infect. 2015;91:28793. DOIPubMedGoogle Scholar
  16. Cole  MJ, Quaye  N, Jacobsson  S, Day  M, Fagan  E, Ison  C, et al. Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data. BMC Infect Dis. 2019;19:281. DOIPubMedGoogle Scholar
  17. Croucher  NJ, Page  AJ, Connor  TR, Delaney  AJ, Keane  JA, Bentley  SD, et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res. 2015;43:e15. DOIPubMedGoogle Scholar
  18. Price  MN, Dehal  PS, Arkin  AP. FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol. 2009;26:164150. DOIPubMedGoogle Scholar
  19. Hunt  M, Mather  AE, Sánchez-Busó  L, Page  AJ, Parkhill  J, Keane  JA, et al. ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads. Microb Genom. 2017;3:e000131. DOIPubMedGoogle Scholar
  20. Sánchez-Busó  L, Golparian  D, Corander  J, Grad  YH, Ohnishi  M, Flemming  R, et al. The impact of antimicrobials on gonococcal evolution. Nat Microbiol. 2019;4:194150. DOIPubMedGoogle Scholar
  21. Unemo  M, Nicholas  RA. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 2012;7:140122. DOIPubMedGoogle Scholar
  22. Fingerhuth  SM, Bonhoeffer  S, Low  N, Althaus  CL. Antibiotic-resistant Neisseria gonorrhoeae spread faster with more treatment, not more sexual partners. PLoS Pathog. 2016;12:e1005611. DOIPubMedGoogle Scholar
  23. Xiridou  M, Soetens  LC, Koedijk  FD, VAN DER Sande  MA, Wallinga  J. Public health measures to control the spread of antimicrobial resistance in Neisseria gonorrhoeae in men who have sex with men. Epidemiol Infect. 2015;143:157584. DOIPubMedGoogle Scholar
  24. Abrams  AJ, Kirkcaldy  RD, Pettus  K, Fox  JL, Kubin  G, Trees  DL. A Case of decreased susceptibility to ceftriaxone in Neisseria gonorrhoeae in the absence of a mosaic penicillin-binding protein 2 (penA) allele. Sex Transm Dis. 2017;44:4924. DOIPubMedGoogle Scholar
  25. Al Suwayyid  BA, Coombs  GW, Speers  DJ, Pearson  J, Wise  MJ, Kahler  CM. Genomic epidemiology and population structure of Neisseria gonorrhoeae from remote highly endemic Western Australian populations. BMC Genomics. 2018;19:165. DOIPubMedGoogle Scholar
  26. Hui  BB, Whiley  DM, Donovan  B, Law  MG, Regan  DG; GRAND Study Investigators. Identifying factors that lead to the persistence of imported gonorrhoeae strains: a modelling study. Sex Transm Infect. 2017;93:2215. DOIPubMedGoogle Scholar
  27. Goldstein  E, Kirkcaldy  RD, Reshef  D, Berman  S, Weinstock  H, Sabeti  P, et al. Factors related to increasing prevalence of resistance to ciprofloxacin and other antimicrobial drugs in Neisseria gonorrhoeae, United States. Emerg Infect Dis. 2012;18:12907. DOIPubMedGoogle Scholar
  28. Donà  V, Smid  JH, Kasraian  S, Egli-Gany  D, Dost  F, Imeri  F, et al. Mismatch amplification mutation assay-based real-time PCR for rapid detection of Neisseria gonorrhoeae and antimicrobial resistance determinants in clinical specimens. J Clin Microbiol. 2018;56:e0036518. DOIPubMedGoogle Scholar
  29. Zhao  L, Liu  A, Li  R, Zhao  S. Multiplex TaqMan real-time PCR platform for detection of Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone. Diagn Microbiol Infect Dis. 2019;93:299304. DOIPubMedGoogle Scholar
  30. Unemo  M, Shafer  WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev. 2014;27:587613. DOIPubMedGoogle Scholar
  31. Chen  SC, Yin  YP, Dai  XQ, Unemo  M, Chen  XS. First nationwide study regarding ceftriaxone resistance and molecular epidemiology of Neisseria gonorrhoeae in China. J Antimicrob Chemother. 2016;71:929. DOIPubMedGoogle Scholar
  32. Zhao  S, Duncan  M, Tomberg  J, Davies  C, Unemo  M, Nicholas  RA. Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2009;53:374451. DOIPubMedGoogle Scholar
  33. Tomberg  J, Unemo  M, Davies  C, Nicholas  RA. Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations. Biochemistry. 2010;49:806270. DOIPubMedGoogle Scholar

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Page updated: February 20, 2020
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