1887

Abstract

Gonorrhoea infections are on the increase and strains that are resistant to all antimicrobials used to treat the disease have been found worldwide. These observations encouraged the World Health Organization to include Neisseria gonorrhoeae on their list of high-priority organisms in need of new treatments. Fortunately, concurrent resistance to both antimicrobials used in dual therapy is still rare. The fight against antimicrobial resistance (AMR) must begin from an understanding of how it evolves and spreads in sexual networks. Genome-based analyses have allowed the study of the gonococcal population dynamics and transmission, giving a novel perspective on AMR gonorrhoea. Here, we will review past, present and future treatment options for gonorrhoea and explain how genomics is helping to increase our understanding of the changing AMR and transmission landscape. This article contains data hosted by Microreact.

Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000239
2019-01-30
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/mgen/5/2/mgen000239.html?itemId=/content/journal/mgen/10.1099/mgen.0.000239&mimeType=html&fmt=ahah

References

  1. Newman L, Rowley J, vander Hoorn S, Wijesooriya NS, Unemo M et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One 2015;10:e0143304 [CrossRef][PubMed]
    [Google Scholar]
  2. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211–1259 [CrossRef][PubMed]
    [Google Scholar]
  3. Unemo M, del Rio C, Shafer WM. Antimicrobial resistance expressed by Neisseria gonorrhoeae: a major global public health problem in the 21st century. Microbiol Spectr 2016;4: [CrossRef][PubMed]
    [Google Scholar]
  4. 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;93:39–45 [CrossRef][PubMed]
    [Google Scholar]
  5. Foster K, Cole M, Hotonu O, Stonebridge J, Hughes G et al. How to do it: lessons identified from investigating and trying to control an outbreak of gonorrhoea in young heterosexual adults. Sex Transm Infect 2016;92:396–401 [CrossRef][PubMed]
    [Google Scholar]
  6. 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 [CrossRef][PubMed]
    [Google Scholar]
  7. World Health Organization, WHO 2012; Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. http://apps.who.int/iris/bitstream/10665/44863/1/9789241503501_eng.pdf
  8. Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev 2014;27:587–613 [CrossRef][PubMed]
    [Google Scholar]
  9. Yokoi S, Deguchi T, Ozawa T, Yasuda M, Ito S et al. Threat to cefixime treatment for gonorrhea. Emerg Infect Dis 2007;13:1275–1277 [CrossRef][PubMed]
    [Google Scholar]
  10. World Health Organization, WHO 2016; WHO guidelines for the treatment of Neisseria gonorrhoeae. http://apps.who.int/iris/bitstream/10665/246114/1/9789241549691-eng.pdf?ua=1
  11. Ohnishi M, Saika T, Hoshina S, Iwasaku K, Nakayama S et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis 2011;17:148–149 [CrossRef][PubMed]
    [Google Scholar]
  12. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A et al. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 2012;56:1273–1280 [CrossRef][PubMed]
    [Google Scholar]
  13. Cámara J, Serra J, Ayats J, Bastida T, Carnicer-Pont D et al. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother 2012;67:1858–1860 [CrossRef][PubMed]
    [Google Scholar]
  14. Lahra MM, Ryder N, Whiley DM. A new multidrug-resistant strain of Neisseria gonorrhoeae in Australia. N Engl J Med 2014;371:1850–1851 [CrossRef][PubMed]
    [Google Scholar]
  15. Lefebvre B, Martin I, Demczuk W, Deshaies L, Michaud S et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Canada. Emerg Infect Dis 20172018;24:
    [Google Scholar]
  16. Jacobsson S, Golparian D, Cole M, Spiteri G, Martin I et al. WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014. J Antimicrob Chemother 2016;71:3109–3116 [CrossRef][PubMed]
    [Google Scholar]
  17. Galarza PG, Alcalá B, Salcedo C, Canigia LF, Buscemi L et al. Emergence of high level azithromycin-resistant Neisseria gonorrhoeae strain isolated in Argentina. Sex Transm Dis 2009;36:787–788 [CrossRef][PubMed]
    [Google Scholar]
  18. Palmer HM, Young H, Winter A, Dave J. Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother 2008;62:490–494 [CrossRef][PubMed]
    [Google Scholar]
  19. Unemo M, Golparian D, Hellmark B. First three Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Sweden: a threat to currently available dual-antimicrobial regimens for treatment of gonorrhea?. Antimicrob Agents Chemother 2014;58:624–625 [CrossRef][PubMed]
    [Google Scholar]
  20. Katz AR, Komeya AY, Soge OO, Kiaha MI, Lee MV et al. Neisseria gonorrhoeae with high-level resistance to azithromycin: case report of the first isolate identified in the United States. Clin Infect Dis 2012;54:841–843 [CrossRef][PubMed]
    [Google Scholar]
  21. Stevens K, Zaia A, Tawil S, Bates J, Hicks V et al. Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Australia. J Antimicrob Chemother 2015;70:1267–1268 [CrossRef][PubMed]
    [Google Scholar]
  22. Chisholm SA, Wilson J, Alexander S, Tripodo F, Al-Shahib A et al. An outbreak of high-level azithromycin resistant Neisseria gonorrhoeae in England. Sex Transm Infect 2016;92:365–367 [CrossRef][PubMed]
    [Google Scholar]
  23. Fifer H, Natarajan U, Jones L, Alexander S, Hughes G et al. Failure of dual antimicrobial therapy in treatment of Gonorrhea. N Engl J Med 2016;374:2504–2506 [CrossRef][PubMed]
    [Google Scholar]
  24. Grad YH, Harris SR, Kirkcaldy RD, Green AG, Marks DS et al. Genomic epidemiology of Gonococcal resistance to extended-spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000-2013. J Infect Dis 2016;214:1579–1587 [CrossRef][PubMed]
    [Google Scholar]
  25. World Health Organization, WHO 2017; Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf
  26. Grad YH, Kirkcaldy RD, Trees D, Dordel J, Harris SR et al. Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect Dis 2014;14:220–226 [CrossRef][PubMed]
    [Google Scholar]
  27. Ohnishi M, Watanabe Y, Ono E, Takahashi C, Oya H et al. Spread of a chromosomal cefixime-resistant penA gene among different Neisseria gonorrhoeae lineages. Antimicrob Agents Chemother 2010;54:1060–1067 [CrossRef][PubMed]
    [Google Scholar]
  28. Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 2011;55:3538–3545 [CrossRef][PubMed]
    [Google Scholar]
  29. Sánchez-Busó L, Grad YH, Golparian D, Unemo M, Ohnishi M et al. Antimicrobial usage drives a double survival strategy in modern gonococcal populations. bioRxiv 2018
    [Google Scholar]
  30. Demczuk W, Lynch T, Martin I, van Domselaar G, Graham M 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;53:191–200 [CrossRef][PubMed]
    [Google Scholar]
  31. Demczuk W, Martin I, Peterson S, Bharat A, van Domselaar G et al. Genomic epidemiology and molecular resistance mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014. J Clin Microbiol 2016;54:1304–1313 [CrossRef][PubMed]
    [Google Scholar]
  32. de Silva D, Peters J, Cole K, Cole MJ, Cresswell F et al. Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study. Lancet Infect Dis 2016;16:1295–1303 [CrossRef][PubMed]
    [Google Scholar]
  33. Didelot X, Dordel J, Whittles LK, Collins C, Bilek N et al. Genomic analysis and comparison of two Gonorrhea Outbreaks. MBio 2016;7: [CrossRef][PubMed]
    [Google Scholar]
  34. Harris SR, Cole MJ, Spiteri G, Sánchez-Busó L, Golparian D et al. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. Lancet Infect Dis 2018;18:758–768 [CrossRef][PubMed]
    [Google Scholar]
  35. Eyre DW, de Silva D, Cole K, Peters J, Cole MJ et al. WGS to predict antibiotic MICs for Neisseria gonorrhoeae. J Antimicrob Chemother 2017;72:1937–1947 [CrossRef][PubMed]
    [Google Scholar]
  36. Shimuta K, Watanabe Y, Nakayama S, Morita-Ishihara T, Kuroki T et al. Emergence and evolution of internationally disseminated cephalosporin-resistant Neisseria gonorrhoeae clones from 1995 to 2005 in Japan. BMC Infect Dis 2015;15:378 [CrossRef][PubMed]
    [Google Scholar]
  37. Yasuda M, Hatazaki K, Ito S, Kitanohara M, Yoh M et al. Antimicrobial susceptibility of Neisseria gonorrhoeae in Japan from 2000 to 2015. Sex Transm Dis 2017;44:149–153 [CrossRef][PubMed]
    [Google Scholar]
  38. Peng T, Lin H, Liu Q, Yang J, Cao W et al. Surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae isolates collected in Changsha, China from 2003 to 2015. Jpn J Infect Dis 2017;70:518–521 [CrossRef][PubMed]
    [Google Scholar]
  39. Lee RS, Seemann T, Heffernan H, Kwong JC, Gonçalves da Silva A et al. Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand. J Antimicrob Chemother 2018;73:353–364 [CrossRef][PubMed]
    [Google Scholar]
  40. Jerse AE, Bash MC, Russell MW. Vaccines against gonorrhea: current status and future challenges. Vaccine 2014;32:1579–1587 [CrossRef][PubMed]
    [Google Scholar]
  41. Petousis-Harris H, Paynter J, Morgan J, Saxton P, McArdle B et al. Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study. Lancet 2017;390:1603–1610 [CrossRef][PubMed]
    [Google Scholar]
  42. Vincent LR, Jerse AE. Biological feasibility and importance of a gonorrhea vaccine for global public health. Vaccine 2018; [CrossRef][PubMed]
    [Google Scholar]
  43. Cempra I. Efficacy and safety study of oral solithromycin compared to intramuscular ceftriaxone plus oral azithromycin in the treatment of patients with gonorrhea (SOLITAIRE-U). 2017; NLM identifier: NCT02210325.https://clinicaltrials.gov/ct2/show/NCT02210325
  44. Kirkcaldy RD, Weinstock HS, Moore PC, Philip SS, Wiesenfeld HC et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis 2014;59:1083–1091 [CrossRef][PubMed]
    [Google Scholar]
  45. Unemo M, Bradshaw CS, Hocking JS, de Vries HJC, Francis SC et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis 2017;17:e235e279 [CrossRef][PubMed]
    [Google Scholar]
  46. Alirol E, Wi TE, Bala M, Bazzo ML, Chen XS et al. Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines. PLoS Med 2017;14:e1002366 [CrossRef][PubMed]
    [Google Scholar]
  47. GTOG 2017; Gentamicin in the treatment of Gonorrhoea. Available fromhttp://www.research.uhb.nhs.uk/gtog
  48. Lagacé-Wiens PRS, Adam HJ, Laing NM, Baxter MR, Martin I et al. Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to alternative antimicrobials with therapeutic potential. J Antimicrob Chemother 2017;72:2273–2277 [CrossRef][PubMed]
    [Google Scholar]
  49. Hamasuna R, Ohnishi M, Matsumoto M, Okumura R, Unemo M et al. In vitro activity of sitafloxacin and additional newer generation fluoroquinolones against ciprofloxacin-resistant Neisseria gonorrhoeae isolates. Microb Drug Resist 2018;24:30–34 [CrossRef][PubMed]
    [Google Scholar]
  50. Weinstock H, Workowski KA. Pharyngeal gonorrhea: an important reservoir of infection?. Clin Infect Dis 2009;49:1798–1800 [CrossRef][PubMed]
    [Google Scholar]
  51. Tuite AR, Gift TL, Chesson HW, Hsu K, Salomon JA et al. Impact of rapid susceptibility testing and antibiotic selection strategy on the emergence and spread of antibiotic resistance in Gonorrhea. J Infect Dis 2017;216:1141–1149 [CrossRef][PubMed]
    [Google Scholar]
  52. Bradley P, Gordon NC, Walker TM, Dunn L, Heys S et al. Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun 2015;6:10063 [CrossRef][PubMed]
    [Google Scholar]
  53. Hunt M, Mather AE, Sánchez-Busó L, Page AJ, Parkhill J et al. ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads. Microb Genom 2017;3:1–11 [CrossRef][PubMed]
    [Google Scholar]
  54. Argimón S, Abudahab K, Goater RJ, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom 2016;2:e000093 [CrossRef][PubMed]
    [Google Scholar]
  55. Ezewudo MN, Joseph SJ, Castillo-Ramirez S, Dean D, del Rio C et al. Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance. PeerJ 2015;3:e806 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000239
Loading
/content/journal/mgen/10.1099/mgen.0.000239
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error