Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

Michaela J. Day; Gianfranco Spiteri; Susanne Jacobsson; Neil Woodford; Andrew J. Amato-Gauci; Michelle J. Cole; Magnus Unemo; Alexander Indra; Steliana Huhlescu; Wim Vanden Berghe; Tania Crucitti; Blaženka Hunjak; Tatjana Nemeth Blažić; Jan Kubele; Hana Zákoucká; Helena Žemličková; Lene Berthelsen; Susan Cowan; Steen Hoffmann; Jevgenia Epstein; Jelena Viktorova; Ndeindo Ndeikoundam; Agathe Goubard; Beatrice Bercot; Peter Kohl; Susanne Buder; Viviane Bremer; Klaus Jansen; Eva Tzelepi; Vasileia Konte; Eszter Balla; M. ria Dudás; Guerún Sigmundsdóttir; Guerún Svanborg Hauksdóttir; Derval Igoe; Brendan Crowley; Barbara Suligoi; Paola Stefanelli; Gatis Pakarna; Violeta Mavcutko; Paul Reichert; Patrick Hoffmann; Christopher Barbara; Francesca Vella; Jackie Maistre Melillo; Alje van Dam; Birgit van Benthem; Ineke Linde; Hilde Kløvstad; Martin Steinbakk; S. awomir Majewski; Jacinta Azevedo; Maria-José Borrego; Peter Pavlik; Peter Truska; Irena Klavs; Samo Jeverica; Julio Vazquez; Asuncion Diaz; Raquel Abad; Inga Velicko; Gwenda Hughes; Kate Templeton; Neil Irvine

doi:https://doi.org/10.1186/s12879-018-3528-4

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

Michaela J. Day, Gianfranco Spiteri, Susanne Jacobsson, Neil Woodford, Andrew J. Amato-Gauci, Michelle J. Cole, Magnus Unemo, Alexander Indra, Steliana Huhlescu, Wim Vanden Berghe, Tania Crucitti, Blaženka Hunjak, Tatjana Nemeth Blažić, Jan Kubele, Hana Zákoucká, Helena Žemličková, Lene Berthelsen, Susan Cowan, Steen Hoffmann, Jevgenia EpsteinJelena Viktorova, Ndeindo Ndeikoundam, Agathe Goubard, Beatrice Bercot, Peter Kohl, Susanne Buder, Viviane Bremer, Klaus Jansen, Eva Tzelepi, Vasileia Konte, Eszter Balla, M. ria Dudás, Guerún Sigmundsdóttir, Guerún Svanborg Hauksdóttir, Derval Igoe, Brendan Crowley, Barbara Suligoi, Paola Stefanelli, Gatis Pakarna, Violeta Mavcutko, Paul Reichert, Patrick Hoffmann, Christopher Barbara, Francesca Vella, Jackie Maistre Melillo, Alje van Dam, Birgit van Benthem, Ineke Linde, Hilde Kløvstad, Martin Steinbakk, S. awomir Majewski, Jacinta Azevedo, Maria-José Borrego, Peter Pavlik, Peter Truska, Irena Klavs, Samo Jeverica, Julio Vazquez, Asuncion Diaz, Raquel Abad, Inga Velicko, Gwenda Hughes, Kate Templeton, Neil Irvine

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Abstract

Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. Results: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. Conclusions: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

Original language	English
Article number	609
Journal	BMC Infectious Diseases
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12879-018-3528-4
Publication status	Published - 2018

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Day, M. J., Spiteri, G., Jacobsson, S., Woodford, N., Amato-Gauci, A. J., Cole, M. J., Unemo, M., Indra, A., Huhlescu, S., Vanden Berghe, W., Crucitti, T., Hunjak, B., Nemeth Blažić, T., Kubele, J., Zákoucká, H., Žemličková, H., Berthelsen, L., Cowan, S., Hoffmann, S., ... Irvine, N. (2018). Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016. BMC Infectious Diseases, 18(1), Article 609. https://doi.org/10.1186/s12879-018-3528-4

@article{ba90b8b19d5d479a8c6547dc710ae7c9,

title = "Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016",

abstract = "Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. Results: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. Conclusions: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.",

author = "Day, {Michaela J.} and Gianfranco Spiteri and Susanne Jacobsson and Neil Woodford and Amato-Gauci, {Andrew J.} and Cole, {Michelle J.} and Magnus Unemo and Alexander Indra and Steliana Huhlescu and {Vanden Berghe}, Wim and Tania Crucitti and Bla{\v z}enka Hunjak and {Nemeth Bla{\v z}i{\'c}}, Tatjana and Jan Kubele and Hana Z{\'a}kouck{\'a} and Helena {\v Z}emli{\v c}kov{\'a} and Lene Berthelsen and Susan Cowan and Steen Hoffmann and Jevgenia Epstein and Jelena Viktorova and Ndeindo Ndeikoundam and Agathe Goubard and Beatrice Bercot and Peter Kohl and Susanne Buder and Viviane Bremer and Klaus Jansen and Eva Tzelepi and Vasileia Konte and Eszter Balla and Dud{\'a}s, {M. ria} and Guer{\'u}n Sigmundsd{\'o}ttir and Hauksd{\'o}ttir, {Guer{\'u}n Svanborg} and Derval Igoe and Brendan Crowley and Barbara Suligoi and Paola Stefanelli and Gatis Pakarna and Violeta Mavcutko and Paul Reichert and Patrick Hoffmann and Christopher Barbara and Francesca Vella and Melillo, {Jackie Maistre} and {van Dam}, Alje and {van Benthem}, Birgit and Ineke Linde and Hilde Kl{\o}vstad and Martin Steinbakk and Majewski, {S. awomir} and Jacinta Azevedo and Maria-Jos{\'e} Borrego and Peter Pavlik and Peter Truska and Irena Klavs and Samo Jeverica and Julio Vazquez and Asuncion Diaz and Raquel Abad and Inga Velicko and Gwenda Hughes and Kate Templeton and Neil Irvine",

year = "2018",

doi = "https://doi.org/10.1186/s12879-018-3528-4",

language = "English",

volume = "18",

journal = "BMC Infectious Diseases",

issn = "1471-2334",

publisher = "BioMed Central",

number = "1",

}

Day, MJ, Spiteri, G, Jacobsson, S, Woodford, N, Amato-Gauci, AJ, Cole, MJ, Unemo, M, Indra, A, Huhlescu, S, Vanden Berghe, W, Crucitti, T, Hunjak, B, Nemeth Blažić, T, Kubele, J, Zákoucká, H, Žemličková, H, Berthelsen, L, Cowan, S, Hoffmann, S, Epstein, J, Viktorova, J, Ndeikoundam, N, Goubard, A, Bercot, B, Kohl, P, Buder, S, Bremer, V, Jansen, K, Tzelepi, E, Konte, V, Balla, E, Dudás, MR, Sigmundsdóttir, G, Hauksdóttir, GS, Igoe, D, Crowley, B, Suligoi, B, Stefanelli, P, Pakarna, G, Mavcutko, V, Reichert, P, Hoffmann, P, Barbara, C, Vella, F, Melillo, JM, van Dam, A, van Benthem, B, Linde, I, Kløvstad, H, Steinbakk, M, Majewski, SA, Azevedo, J, Borrego, M-J, Pavlik, P, Truska, P, Klavs, I, Jeverica, S, Vazquez, J, Diaz, A, Abad, R, Velicko, I, Hughes, G, Templeton, K & Irvine, N 2018, 'Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016', BMC Infectious Diseases, vol. 18, no. 1, 609. https://doi.org/10.1186/s12879-018-3528-4

TY - JOUR

T1 - Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

AU - Day, Michaela J.

AU - Spiteri, Gianfranco

AU - Jacobsson, Susanne

AU - Woodford, Neil

AU - Amato-Gauci, Andrew J.

AU - Cole, Michelle J.

AU - Unemo, Magnus

AU - Indra, Alexander

AU - Huhlescu, Steliana

AU - Vanden Berghe, Wim

AU - Crucitti, Tania

AU - Hunjak, Blaženka

AU - Nemeth Blažić, Tatjana

AU - Kubele, Jan

AU - Zákoucká, Hana

AU - Žemličková, Helena

AU - Berthelsen, Lene

AU - Cowan, Susan

AU - Hoffmann, Steen

AU - Epstein, Jevgenia

AU - Viktorova, Jelena

AU - Ndeikoundam, Ndeindo

AU - Goubard, Agathe

AU - Bercot, Beatrice

AU - Kohl, Peter

AU - Buder, Susanne

AU - Bremer, Viviane

AU - Jansen, Klaus

AU - Tzelepi, Eva

AU - Konte, Vasileia

AU - Balla, Eszter

AU - Dudás, M. ria

AU - Sigmundsdóttir, Guerún

AU - Hauksdóttir, Guerún Svanborg

AU - Igoe, Derval

AU - Crowley, Brendan

AU - Suligoi, Barbara

AU - Stefanelli, Paola

AU - Pakarna, Gatis

AU - Mavcutko, Violeta

AU - Reichert, Paul

AU - Hoffmann, Patrick

AU - Barbara, Christopher

AU - Vella, Francesca

AU - Melillo, Jackie Maistre

AU - van Dam, Alje

AU - van Benthem, Birgit

AU - Linde, Ineke

AU - Kløvstad, Hilde

AU - Steinbakk, Martin

AU - Majewski, S. awomir

AU - Azevedo, Jacinta

AU - Borrego, Maria-José

AU - Pavlik, Peter

AU - Truska, Peter

AU - Klavs, Irena

AU - Jeverica, Samo

AU - Vazquez, Julio

AU - Diaz, Asuncion

AU - Abad, Raquel

AU - Velicko, Inga

AU - Hughes, Gwenda

AU - Templeton, Kate

AU - Irvine, Neil

PY - 2018

Y1 - 2018

N2 - Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. Results: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. Conclusions: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

AB - Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. Results: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. Conclusions: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30509194

U2 - https://doi.org/10.1186/s12879-018-3528-4

DO - https://doi.org/10.1186/s12879-018-3528-4

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C2 - 30509194

SN - 1471-2334

VL - 18

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

IS - 1

M1 - 609

ER -

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

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