Skip to main content

Advertisement

SpringerLink
Log in

Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The aims of this study were to determine the antimicrobial susceptibility of Neisseria gonorrhoeae (NG) in our area, to analyze the molecular mechanisms involved in cephalosporins resistance, and to undertake molecular typing of our NG strains. Antimicrobial susceptibility was determined using the Etest. The genes penA, mtrR, penB, and ponA were studied. Molecular typing was performed by N. gonorrhoeae multiantigen sequence typing. Of 329 strains analyzed in 2013, none showed high-level cephalosporin resistance, but 8.2 % had resistance to cefixime [minimum inhibitory concentration (MIC) > 0.125 μg/mL] and 0.6 % to ceftriaxone (MIC > 0.125 μg/mL). Azithromycin resistance was documented in 4.3 % and ciprofloxacin resistance in 49.2 %. Among 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 58.3 % showed the penA mosaic pattern XXXIV, 98 % a Leu → Pro substitution at position 421 of the ponA gene, 100 % amino acid changes at positions 101 and 102 of the PorB1b porin, and 87.5 % of strains an adenine deletion in the promoter region of the MtrC-D-E efflux pump. A significant difference between strains with and without decreased cephalosporin susceptibility (MIC ≥ 0.125 μg/mL) was observed for these four genes. Of the 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 43.8 % belonged to the genogroup G1407 and 27.1 % belonged to the genogroup G2400. A significant association of G1407 with decreased susceptibility (MIC ≥ 0.125 μg/mL) and G2992 with susceptibility was found, and also between G1407 and mosaic pattern XXXIV and between G2400 and A501T substitution in penA. The NG resistance rate in our area is higher than the median of Europe. We have detected the emergence of G2400, which may be a source of antimicrobial resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Unemo M, Nicholas RA (2012) Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol 7(12):1401–1422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Barry PM, Klausner JD (2009) The use of cephalosporins for gonorrhea: the impending problem of resistance. Expert Opin Pharmacother 10(4):555–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bolan GA, Sparling PF, Wasserheit JN (2012) The emerging threat of untreatable gonococcal infection. N Engl J Med 366(6):485–487

    Article  PubMed  Google Scholar 

  4. Papp JR, Schachter J, Gaydos CA et al (2014) Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae—2014. MMWR 63:1–19

    PubMed Central  Google Scholar 

  5. Cole MJ, Spiteri G, Chisholm SA et al (2014) Emerging cephalosporin and multidrug-resistant gonorrhoea in Europe. Euro Surveill 19(45):20955

    Article  CAS  PubMed  Google Scholar 

  6. Ison CA, Hussey J, Sankar KN et al (2011) Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010. Euro Surveill 16(14). pii: 19833

  7. Ohnishi M, Golparian D, Shimuta K et al (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(7):3538–3545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Unemo M, Golparian D, Hestner A (2011) Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010. Euro Surveill 16(6). pii: 19792

  9. Unemo M, Golparian D, Nicholas R et al (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(3):1273–1280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Unemo M, Golparian D, Stary A et al (2011) First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhoea treatment failure in Austria, 2011. Euro Surveill 16(43). pii: 19998

  11. Carnicer-Pont D, Smithson A, Fina-Homar E et al (2012) First cases of Neisseria gonorrhoeae resistant to ceftriaxone in Catalonia, Spain, May 2011. Enferm Infecc Microbiol Clin 30(4):218–219

    Article  PubMed  Google Scholar 

  12. Cámara J, Serra J, Ayats J et al (2012) Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother 67(8):1858–1860

    Article  PubMed  Google Scholar 

  13. European Centre for Disease Prevention and Control (ECDC) (2015) Gonococcal antimicrobial susceptibility surveillance in Europe, 2013. ECDC, Stockholm

    Google Scholar 

  14. Chisholm SA, Unemo M, Quaye N et al (2013) Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone. Euro Surveill 18(3). pii: 20358

  15. Unemo M, Golparian D, Syversen G et al (2010) Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhoea treatment, Norway, 2010. Euro Surveill 15(47). pii: 19721

  16. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 3.1, valid from 2013-02-11, pp 50–53. Available online at: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/Breakpoint_table_v_3.1.pdf

  17. Tanaka M, Nakayama H, Huruya K et al (2006) Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype. Int J Antimicrob Agents 27(1):20–26

    Article  CAS  PubMed  Google Scholar 

  18. Allen VG, Farrell DJ, Rebbapragada A et al (2011) Molecular analysis of antimicrobial resistance mechanisms in Neisseria gonorrhoeae isolates from Ontario, Canada. Antimicrob Agents Chemother 55(2):703–712

    Article  CAS  PubMed  Google Scholar 

  19. Unemo M, Olcén P, Berglund T et al (2002) Molecular epidemiology of Neisseria gonorrhoeae: sequence analysis of the porB gene confirms presence of Two circulating strains. J Clin Microbiol 40(10):3741–3749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Martin IM, Ison CA, Aanensen DM et al (2004) Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis 189(8):1497–1505

    Article  CAS  PubMed  Google Scholar 

  21. Chen C-C, Lin K-Y, Li S-Y (2012) The role of penicillin-binding protein 2 (PBP2) in the cephalosporin susceptibility of Neisseria gonorrhoeae and the need for consensus in naming of PBP2. J Formos Med Assoc 111(12):665–666

    Article  CAS  PubMed  Google Scholar 

  22. Serra-Pladevall J, Barberá-Gracia MJ, Roig-Carbajosa G et al (2013) Neisseria gonorrhoeae: resistencias antimicrobianas y estudio de la dinámica poblacional. Situación en 2011 en Barcelona. Enferm Infecc Microbiol Clin 31(9):579–583

    Article  PubMed  Google Scholar 

  23. Zhao S, Duncan M, Tomberg J et al (2009) Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother 53(9):3744–3751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ropp PA, Hu M, Olesky M et al (2002) Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 46(3):769–777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Thakur SD, Starnino S, Horsman GB et al (2014) Unique combined penA/mtrR/porB mutations and NG-MAST strain types associated with ceftriaxone and cefixime MIC increases in a ‘susceptible’ Neisseria gonorrhoeae population. J Antimicrob Chemother 69(6):1510–1516

    Article  CAS  PubMed  Google Scholar 

  26. Martin I, Sawatzky P, Allen V et al (2012) Emergence and characterization of Neisseria gonorrhoeae isolates with decreased susceptibilities to ceftriaxone and cefixime in Canada: 2001–2010. Sex Transm Dis 39(4):316–323

    Article  PubMed  Google Scholar 

  27. Lindberg R, Fredlund H, Nicholas R et al (2007) Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime and ceftriaxone: association with genetic polymorphisms in penA, mtrR, porB1b, and ponA. Antimicrob Agents Chemother 51(6):2117–2122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Heymans R, Bruisten SM, Golparian D et al (2012) Clonally related Neisseria gonorrhoeae isolates with decreased susceptibility to the extended-spectrum cephalosporin cefotaxime in amsterdam, the Netherlands. Antimicrob Agents Chemother 56(3):1516–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Carannante A, Renna G, Dal Conte I et al (2014) Changing antimicrobial resistance profiles among Neisseria gonorrhoeae isolates in Italy, 2003 to 2012. Antimicrob Agents Chemother 58(10):5871–5876

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jeverica S, Golparian D, Matičič M et al (2014) Phenotypic and molecular characterization of Neisseria gonorrhoeae isolates from Slovenia, 2006–12: rise and fall of the multidrug-resistant NG-MAST genogroup 1407 clone? J Antimicrob Chemother 69(6):1517–1525

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microbiology Department, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron, 119–129, 08035, Barcelona, Spain

    J. Serra-Pladevall, R. Bartolomé-Comas, G. Roig, R. Juvé & A. Andreu

  2. Genetics and Microbiology Department, Universitat Autonoma de Barcelona, Cerdanyola, Spain

    J. Serra-Pladevall, R. Bartolomé-Comas & A. Andreu

  3. Infectious Disease Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    M. J. Barberá

  4. Universitat de Barcelona, Barcelona, Spain

    S. Rodriguez

Authors
  1. J. Serra-Pladevall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. J. Barberá
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Bartolomé-Comas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Roig
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Juvé
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Andreu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Serra-Pladevall.

Ethics declarations

Funding

This study was funded by a grant (PI12/01808) from Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Serra-Pladevall, J., Barberá, M.J., Rodriguez, S. et al. Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins. Eur J Clin Microbiol Infect Dis 35, 1549–1556 (2016). https://doi.org/10.1007/s10096-016-2696-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-016-2696-7

Keywords

Search

Navigation