Cited by 49Antibiotic Resistance in BacteriaReproductive tract infections researchBacterial Infections and Vaccines

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Global Transmission of the penA Allele 60.001–Containing High-Level Ceftriaxone-Resistant Gonococcal FC428 Clone and Antimicrobial Therapy of Associated Cases: A Review

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van der Veen, Stijn·2023·Infectious Microbes and Diseases

Abstract

Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line therapy. However, ceftriaxone susceptibility has been waning in a number of countries over the last decade and ceftriaxone treatment failures have been reported, commonly as a result of sporadic high-level ceftriaxone-resistant strains. In recent years, N. gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or strains that acquired its main ceftriaxone resistance determinant, penA allele 60.001, have shown global transmission, resulting in ceftriaxone treatment failure in a number of cases. The FC428 clone was first encountered in Japan in 2015 and subsequently in China, Europe, Australia, North America and Southeast Asia afterward. Strains associated with the FC428 clone commonly display a ceftriaxone minimum inhibitory concentration of 0.5–1 mg/L. However, where penA alleles encountered in sporadic high-level ceftriaxone-resistant isolates induce an in vitro growth defect, penA allele 60.001 does not seem to affect in vitro growth. The limited impact of penA allele 60.001 on biological fitness might be associated with its successful global transmission. Although the FC428 clone displays high-level ceftriaxone resistance, most gonorrhea cases associated with this clone were still successfully cured with ceftriaxone when intramuscular or intravenous doses of 500 mg to 2 g were used. A successful alternative therapy seems to be ertapenem given at 1-g doses, although further clinical studies are required to validate ertapenem efficacy. This review summarizes the global transmission of strains associated with the FC428 clone and antimicrobial treatment of associated cases.

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Research works printed but not linked: 51

  1. 2019, Kissing, saliva exchange, and transmission of Neisseria gonorrhoeae, Lancet Infect Dis, 19, e367, 10.1016/S1473-3099(19)30306-8 · DOI
  2. 2019, Gonorrhoea, Nat Rev Dis Primers, 5, 79, 10.1038/s41572-019-0128-6 · DOI
  3. 2020, Antibiotic resistance and treatment options for multidrug-resistant gonorrhea, Infect Microb Dis, 2, 67, 10.1097/IM9.0000000000000024 · DOI
  4. 2013, Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007–2011, Lancet Infect Dis, 13, 762, 10.1016/S1473-3099(13)70143-9 · DOI
  5. 2015, Emergence and evolution of internationally disseminated cephalosporin-resistant Neisseria gonorrhoeae clones from 1995 to 2005 in Japan, BMC Infect Dis, 15, 378, 10.1186/s12879-015-1110-x · DOI
  6. 2019, Increasing prevalence of Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone and resistance to azithromycin in Hangzhou, China (2015–17), J Antimicrob Chemother, 74, 29
  7. 2018, Susceptibility of Neisseria gonorrhoeae to azithromycin and ceftriaxone in China: a retrospective study of national surveillance data from 2013 to 2016, PLoS Med, 15, e1002499, 10.1371/journal.pmed.1002499 · DOI
  8. 2013, Failure of 500 mg of ceftriaxone to eradicate pharyngeal gonorrhoea, Australia, J Antimicrob Chemother, 68, 1445, 10.1093/jac/dkt017 · DOI
  9. 2018, Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017, Euro Surveill, 23, 1800264
  10. 2009, Two cases of failed ceftriaxone treatment in pharyngeal gonorrhoea verified by molecular microbiological methods, J Med Microbiol, 58, 683
  11. 2011, Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010, Euro Surveill, 16, 19792
  12. 2012, 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, 56, 1273, 10.1128/AAC.05760-11 · DOI
  13. 2012, Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011, Euro Surveill, 17, 20200
  14. 2012, Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain, J Antimicrob Chemother, 67, 1858, 10.1093/jac/dks162 · DOI
  15. 2016, New clinical strain of Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone, Japan, Emerg Infect Dis, 22, 142, 10.3201/eid2201.150868 · DOI
  16. 2014, A new multidrug-resistant strain of Neisseria gonorrhoeae in Australia, N Engl J Med, 371, 1850, 10.1056/NEJMc1408109 · DOI
  17. 2011, 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, 55, 3538, 10.1128/AAC.00325-11 · DOI
  18. 2019, Genetic characterization and enhanced surveillance of ceftriaxone-resistant Neisseria gonorrhoeae strain, Alberta, Canada, 2018, Emerg Infect Dis, 25, 1660, 10.3201/eid2509.190407 · DOI
  19. 2018, Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018, Euro Surveill, 23, 1800323
  20. 2019, Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018, Euro Surveill, 24, 1900147
  21. 2022, Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022, Euro Surveill, 27, 2200455
  22. 2016, New ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain with a novel mosaic penA gene isolated in Japan, Antimicrob Agents Chemother, 60, 4339, 10.1128/AAC.00504-16 · DOI
  23. 2011, A novel mechanism of high-level, broad-spectrum antibiotic resistance caused by a single base pair change in Neisseria gonorrhoeae, MBio, 2, e00187
  24. 2013, Identification of amino acids conferring high-level resistance to expanded-spectrum cephalosporins in the penA gene from Neisseria gonorrhoeae strain H041, Antimicrob Agents Chemother, 57, 3029, 10.1128/AAC.00093-13 · DOI
  25. 2018, In vivo-selected compensatory mutations restore the fitness cost of mosaic penA alleles that confer ceftriaxone resistance in Neisseria gonorrhoeae, MBio, 9, e01905
  26. 2017, Alanine 501 mutations in penicillin-binding protein 2 from Neisseria gonorrhoeae: structure, mechanism, and effects on cephalosporin resistance and biological fitness, Biochemistry, 56, 1140, 10.1021/acs.biochem.6b01030 · DOI
  27. 2020, Emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains harbouring a novel mosaic penA gene in China, J Antimicrob Chemother, 75, 907, 10.1093/jac/dkz530 · DOI
  28. 2019, Identification of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, China, Emerg Infect Dis, 25, 1427, 10.3201/eid2507.190172 · DOI
  29. 2019, Detection and analysis of two cases of the internationally spreading ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in China, J Antimicrob Chemother, 74, 3635, 10.1093/jac/dkz384 · DOI
  30. 2020, Sustained transmission of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in China, J Antimicrob Chemother, 75, 2499, 10.1093/jac/dkaa196 · DOI
  31. 2022, Dissemination and genome analysis of high-level ceftriaxone-resistant penA 60.001 Neisseria gonorrhoeae strains from the Guangdong gonococcal antibiotics susceptibility Programme (GD-GASP), 2016–2019, Emerg Microbes Infect, 11, 344, 10.1080/22221751.2021.2011618 · DOI
  32. 2021, High percentage of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone among isolates from a single hospital in Hangzhou, China, J Antimicrob Chemother, 76, 936, 10.1093/jac/dkaa526 · DOI
  33. 2018, Cooperative recognition of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain, Emerg Infect Dis, 24, 735
  34. 2018, Ceftriaxone-resistant Neisseria gonorrhoeae, Canada, 2017, Emerg Infect Dis, 24, 381, 10.3201/eid2402.171756 · DOI
  35. 2017, Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017, Euro Surveill, 22, 17
  36. 2018, Multidrug-resistant Neisseria gonorrhoeae isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018, Euro Surveill, 23, 1800617
  37. 2019, First case of ceftriaxone-resistant multidrug-resistant Neisseria gonorrhoeae in Singapore, Antimicrob Agents Chemother, 63, e02624
  38. 2022, Neisseria gonorrhoeae FC428 Subclone, Vietnam, 2019–2020, Emerg Infect Dis, 28, 432, 10.3201/eid2802.211788 · DOI
  39. 2020, Impact of the gonococcal FC428 penA allele 60.001 on ceftriaxone resistance and biological fitness, Emerg Microbes Infect, 9, 1219, 10.1080/22221751.2020.1773325 · DOI
  40. 2019, Recognition of the β-lactam carboxylate triggers acylation of Neisseria gonorrhoeae penicillin-binding protein 2, J Biol Chem, 294, 14020, 10.1074/jbc.RA119.009942 · DOI
  41. 2010, 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, 49, 8062, 10.1021/bi101167x · DOI
  42. 2019, Clonal expansion and spread of the ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, identified in Japan in 2015, and closely related isolates, J Antimicrob Chemother, 74, 1812, 10.1093/jac/dkz129 · DOI
  43. 2022, Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial, Lancet Infect Dis, 22, 706, 10.1016/S1473-3099(21)00625-3 · DOI
  44. 2020, NG-STAR genotypes are associated with MDR in Neisseria gonorrhoeae isolates collected in 2017 in Shanghai, J Antimicrob Chemother, 75, 566, 10.1093/jac/dkz471 · DOI
  45. 2019, Identification of multidrug-resistant Neisseria gonorrhoeae isolates with combined resistance to both ceftriaxone and azithromycin, China, 2017–2018, Emerg Microbes Infect, 8, 1546, 10.1080/22221751.2019.1681242 · DOI
  46. 2020, Emergence and genomic characterization of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in Chengdu, China, J Antimicrob Chemother, 75, 2495, 10.1093/jac/dkaa123 · DOI
  47. 2022, Emergence and genomic characterization of Neisseria gonorrhoeae isolates with high levels of ceftriaxone and azithromycin resistance in Guangdong, China, from 2016 to 2019, Microbiol Spectr, 10, e0157022, 10.1128/spectrum.01570-22 · DOI
  48. 2021, Emergence and characterization of a ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone evolving moderate-level resistance to azithromycin in Shenzhen, China, Infect Drug Resist, 14, 4271, 10.2147/IDR.S336212 · DOI
  49. 2019, Two cases of multidrug-resistant Neisseria gonorrhoeae related to travel in South-Eastern Asia, France, June 2019, Euro Surveill, 24, 1900528
  50. 2018, Genetic characterisation of Neisseria gonorrhoeae resistant to both ceftriaxone and azithromycin, Lancet Infect Dis, 18, 717, 10.1016/S1473-3099(18)30340-2 · DOI
  51. 2020, Evaluation of alternative antibiotics for susceptibility of gonococcal isolates from China, Int J Antimicrob Agents, 55, 105846, 10.1016/j.ijantimicag.2019.11.003 · DOI

Metadata

Authors
van der Veen, S.
Affiliations
Sir Run Run Shaw Hospital (CN)
Corresponding author
van der Veen, Stijn
Venue
Infectious Microbes and Diseases
Published
2023-01-23
Volume
5
Issue
1
Pages
13-20
ISSN
  • 2096-7241 (ISSN-L)
  • 2641-5917
OpenAlex
W4318995840
Cited by
49
References
0
Citations by year
2026: 15 · 2025: 17 · 2024: 15 · 2023: 2
FWCI
0.92
Type
journal article
Language
en
Open access
Locations
Infectious Microbes & Diseases (publishedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
Neisseria gonorrhoeae, gonorrhea, ceftriaxone resistance, global transmission, antimicrobial therapy, ertapenem, multidrug resistance, bacterial fitness

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