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

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

Title: Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019
Author: The Euro-GASP network
Date: 2022-06-07
Language: English
Scope: 968942
Department: Faculty of Medicine
Clinical Laboratory Services, Diagnostics and Blood Bank
Series: BMC Infectious Diseases; 22(1)
ISSN: 1471-2334
DOI: 10.1186/s12879-022-07509-w
Subject: Anti-Bacterial Agents/pharmacology; Anti-Infective Agents/therapeutic use; Azithromycin/pharmacology; Cefixime/pharmacology; Ceftriaxone/pharmacology; Ciprofloxacin/pharmacology; Drug Resistance, Bacterial; Female; Gonorrhea/drug therapy; Homosexuality, Male; Humans; Male; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Pharyngitis/drug therapy; Sexual and Gender Minorities
URI: https://hdl.handle.net/20.500.11815/3746

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The Euro-GASP network 2022 , ' Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019 ' , BMC Infectious Diseases , vol. 22 , no. 1 , 524 , pp. 524 . https://doi.org/10.1186/s12879-022-07509-w


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.


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).

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