Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 9/2016

01-09-2016 | Original Article

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

Authors: J. Serra-Pladevall, M. J. Barberá, S. Rodriguez, R. Bartolomé-Comas, G. Roig, R. Juvé, A. Andreu

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 9/2016

Login to get access

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.
Literature
1.
2.
3.
go back to reference Bolan GA, Sparling PF, Wasserheit JN (2012) The emerging threat of untreatable gonococcal infection. N Engl J Med 366(6):485–487CrossRefPubMed Bolan GA, Sparling PF, Wasserheit JN (2012) The emerging threat of untreatable gonococcal infection. N Engl J Med 366(6):485–487CrossRefPubMed
4.
go back to reference Papp JR, Schachter J, Gaydos CA et al (2014) Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae—2014. MMWR 63:1–19PubMedCentral Papp JR, Schachter J, Gaydos CA et al (2014) Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae—2014. MMWR 63:1–19PubMedCentral
5.
go back to reference Cole MJ, Spiteri G, Chisholm SA et al (2014) Emerging cephalosporin and multidrug-resistant gonorrhoea in Europe. Euro Surveill 19(45):20955CrossRefPubMed Cole MJ, Spiteri G, Chisholm SA et al (2014) Emerging cephalosporin and multidrug-resistant gonorrhoea in Europe. Euro Surveill 19(45):20955CrossRefPubMed
6.
go back to reference 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 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.
go back to reference 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):3538–3545CrossRefPubMedPubMedCentral 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):3538–3545CrossRefPubMedPubMedCentral
8.
go back to reference 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 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.
go back to reference 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):1273–1280CrossRefPubMedPubMedCentral 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):1273–1280CrossRefPubMedPubMedCentral
10.
go back to reference 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 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.
go back to reference 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):218–219CrossRefPubMed 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):218–219CrossRefPubMed
12.
go back to reference 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):1858–1860CrossRefPubMed 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):1858–1860CrossRefPubMed
13.
go back to reference European Centre for Disease Prevention and Control (ECDC) (2015) Gonococcal antimicrobial susceptibility surveillance in Europe, 2013. ECDC, Stockholm European Centre for Disease Prevention and Control (ECDC) (2015) Gonococcal antimicrobial susceptibility surveillance in Europe, 2013. ECDC, Stockholm
14.
go back to reference 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 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.
go back to reference 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 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
17.
go back to reference 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):20–26CrossRefPubMed 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):20–26CrossRefPubMed
18.
go back to reference 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):703–712CrossRefPubMed 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):703–712CrossRefPubMed
19.
go back to reference 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):3741–3749CrossRefPubMedPubMedCentral 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):3741–3749CrossRefPubMedPubMedCentral
20.
go back to reference 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):1497–1505CrossRefPubMed 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):1497–1505CrossRefPubMed
21.
go back to reference 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):665–666CrossRefPubMed 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):665–666CrossRefPubMed
22.
go back to reference 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):579–583CrossRefPubMed 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):579–583CrossRefPubMed
23.
go back to reference 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):3744–3751CrossRefPubMedPubMedCentral 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):3744–3751CrossRefPubMedPubMedCentral
24.
go back to reference 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):769–777CrossRefPubMedPubMedCentral 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):769–777CrossRefPubMedPubMedCentral
25.
go back to reference 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):1510–1516CrossRefPubMed 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):1510–1516CrossRefPubMed
26.
go back to reference 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):316–323CrossRefPubMed 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):316–323CrossRefPubMed
27.
go back to reference 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):2117–2122CrossRefPubMedPubMedCentral 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):2117–2122CrossRefPubMedPubMedCentral
28.
go back to reference 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):1516–1522CrossRefPubMedPubMedCentral 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):1516–1522CrossRefPubMedPubMedCentral
29.
go back to reference 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):5871–5876CrossRefPubMedPubMedCentral 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):5871–5876CrossRefPubMedPubMedCentral
30.
go back to reference 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):1517–1525CrossRefPubMed 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):1517–1525CrossRefPubMed
Metadata
Title
Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins
Authors
J. Serra-Pladevall
M. J. Barberá
S. Rodriguez
R. Bartolomé-Comas
G. Roig
R. Juvé
A. Andreu
Publication date
01-09-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 9/2016
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-016-2696-7

Other articles of this Issue 9/2016

European Journal of Clinical Microbiology & Infectious Diseases 9/2016 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.