Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019

Funding Information: We are grateful to the European STI surveillance network for its contribution to developing and implementing Euro-GASP and submitting gonococcal isolates and epidemiological data. The Euro-GASP Network: Austrian Agency for Health and Food Safety, Wien, Austria: Claudia Eder, Sonja Pleininger, Steliana Huhlescu; Institute of Tropical Medicine, Antwerpen, Belgium: Irith de Baetselier; Croatian National Institute Of Public Health, Zagreb, Croatia: Blaženka Hunjak, Tatjana Nemeth Blažić; Nicosia General Hospital, Nicosia, Cyprus: Panagiota Maikanti-Charalampous, Despo Pieridou; The National Institute of Public Health, Prague, The Czech Republic: Hana Zákoucká, Helena Žemličková; Statens Serum Institut, Copenhagen, Denmark: Steen Hoffmann, Susan Cowan; Health Board, Tallinn, Estonia: Rita Peetso, Jelena Viktorova; Hospital Saint Louis, Paris, France: Ndeindo Ndeikoundam, Beatrice Bercot; Helsinki University Central Hospital, Helsinki, Finland: Anu Patari Sampo, Vesa Kirjavainen; Vivantes Klinikum Neukolln, Berlin, Germany: Susanne Buder, Klaus Jansen; Hellenic Pasteur Institute, Athens, Greece: Vivi Miriagou; National Centre for Epidemiology, Budapest, Hungary: Eszter Balla, Mária Dudás; Landspitali University Hospital, Reykjavik, Iceland: Guðrún Sigmundsdóttir, Lena Ros Asmundsdottir; St James's Hospital, Dublin, Ireland: Sinead Saab, Brendan Crowley; Istituto Superiore di Sanita, Rome, Italy: Anna Carannante, Paola Stefanelli; Riga East University Hospital, Riga, Latvia: Gatis Pakarna, Violeta Mavcutko; Mater Dei Hospital, Msida, Malta: Robert Cassar, Christopher Barbara, Francesca Vella; The Public Health Service of Amsterdam, Amsterdam, The Netherlands: Alje Van Dam, Ineke Linde; Domain of Infectious Disease Control and Environmental Health, Oslo, Norway: Dominique Caugant, Hilde Kløvstad; Medical University of Warsaw, Warsaw, Poland: Beata Mlynarczyk-Bonikowska; Instituto Nacional de Saude Dr Ricardo Jorge, Lisboa, Portugal: Maria-José Borrego; Medirex a.s., Bratislava, Slovak Republic: Peter Pavlik; Institut za mikrobiologijo in imunologijo, Univerza v Ljubljani Medicinska fakulteta, Ljubljana, Slovenia: Irena Klavs, Tanja Kustec; National Institute of Health Carlos III, Madrid, Spain: Julio Vazquez, Asuncion Diaz, Raquel Abad Torreblanca; Public Health Agency of Sweden, Stockholm, Sweden: Inga Velicko, Magnus Unemo; Royal Infirmary of Edinburgh, Edinburgh, UK: Helen Fifer, Kate Templeton. Funding Information: The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2017/004). The funding body designed, initiated and coordinated the study as well as assisted in the interpretation of the data, development and final approval of the manuscript. Publisher Copyright: © 2022, The Author(s).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 2019 (26 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 clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance. Results: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age. Conclusions: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin “resistance” (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.Peer reviewe

Significant increase in azithromycin "resistance" and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019

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 2019 (26 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 clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance. Results: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age. Conclusions: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2017/004). The funding body designed, initiated and coordinated the study as well as assisted in the interpretation of the data, development and final approval of the manuscriptS

Associations between antimicrobial susceptibility/resistance of Neisseria gonorrhoeae isolates in European Union/European Economic Area and patients’ gender, sexual orientation and anatomical site of infection, 2009–2016

Funding Information: We would like to thank the members of the European STI network for their active participation in Euro-GASP: Austria: Claudia Eder, Sonja Pleininger, Alexander Indra, Steliana Huhlescu; Belgium: Irith De Baetselier, Wim Vanden Berghe; Croatia: Bla?enka Hunjak, Tatjana Nemeth Bla?i?; Cyprus: Panayiota Maikanti-Charalambous, Despo Pieridou; Czech Republic: Hana Z?kouck?, Helena ?emli?kov?; Denmark: Steen Hoffmann, Lasse Jessen Schwartz; Estonia: Rita Peetso, Jevgenia Epstein, Jelena Viktorova; France: Ndeindo Ndeikoundam, Beatrice Bercot, C?cile B?b?ar, Florence Lot; Germany: Susanne Buder, Klaus Jansen; Greece: Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos; Hungary: Eszter Balla, M?ria Dud?s; Iceland: Lena R?s ?smundsd?ttir, Gu?r?n Sigmundsd?ttir, Gu?r?n Svanborg Hauksd?ttir, Thorolfur Gudnason; Ireland: Aoife Colgan, Brendan Crowley, Sin?ad Saab; Italy: Paola Stefanelli, Anna Carannante, Patrizia Parodi; Latvia: Gatis Pakarna, Raina Nikiforova, Antra Bormane, Elina Dimina; Luxembourg: Monique Perrin, Tamir Abdelrahman, Jo?l Mossong, Jean-Claude Schmit, Friedrich M?hlschlegel; Malta: Christopher Barbara, Francesca Mifsud; the Netherlands: Alje Van Dam, Birgit Van Benthem, Maartje Visser, Ineke Linde; Norway: Hilde Kl?vstad, Dominique Caugant; Poland: Beata M?ynarczyk-Bonikowska; Portugal: Jacinta Azevedo, Maria-Jos? Borrego, Marina Lurdes Ramos Nascimento; Slovak Republic: Peter Pavlik; Slovenia: Irena Klavs, Andreja Murnik, Samo Jeverica, Sandra Kosmac, Tanja Kustec; Spain: Julio V?zquez Moreno, Asuncion Diaz, Raquel Abad; Sweden: Inga Velicko, Magnus Unemo; United Kingdom: Gwenda Hughes, Jill Shepherd, Lynsey Patterson. Publisher Copyright: © 2021, The Author(s).BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae, nationally and internationally, is a serious threat to the management and control of gonorrhoea. Limited and conflicting data regarding the epidemiological drivers of gonococcal AMR internationally have been published. We examined the antimicrobial susceptibility/resistance of gonococcal isolates (n = 15,803) collected across 27 European Union/European Economic Area (EU/EEA) countries in 2009-2016, in conjunction to epidemiological and clinical data of the corresponding patients, to elucidate associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection. METHODS: In total, 15,803 N. gonorrhoeae isolates from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 2009-2016, were examined. Associations between gonococcal susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection were investigated using univariate and multivariate logistic regression analysis. Statistical significance was determined by Pearson χ 2-test or Fisher's exact test with two-tailed p-values of < 0.05 indicating significance. RESULTS: The overall gonococcal resistance from 2009 to 2016 was 51.7% (range during the years: 46.5-63.5%), 7.1% (4.5-13.2%), 4.3% (1.8-8.7%), and 0.2% (0.0-0.5%) to ciprofloxacin, azithromycin, cefixime, and ceftriaxone, respectively. The level of resistance combined with decreased susceptibility to ceftriaxone was 10.2% (5.7-15.5%). Resistance to cefixime and ciprofloxacin, and resistance combined with decreased susceptibility to ceftriaxone were positively associated with urogenital infections and heterosexual males, males with sexual orientation not reported and females (except for ciprofloxacin), i.e. when compared to men-who-have-sex-with-men (MSM). Azithromycin resistance was positively associated with heterosexual males, but no association was significant regarding anatomical site of infection. CONCLUSIONS: Overall, sexual orientation was the main variable associated with gonococcal AMR. Strongest positive associations were identified with heterosexual patients, particularly males, and not MSM. To provide evidence-based understanding and mitigate gonococcal AMR emergence and spread, associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection need to be further investigated in different geographic settings. In general, these insights will support identification of groups at increased risk and targeted public health actions such as intensified screening, 3-site testing using molecular diagnostics, sexual contact tracing, and surveillance of treatment failures.Peer reviewe