Browsing by Author "Bercot, Beatrice"
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- Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance studyPublication . Sánchez-Busó, Leonor; Cole, Michelle J.; Spiteri, Gianfranco; Day, Michaela; Jacobsson, Susanne; Golparian, Daniel; Sajedi, Noshin; Yeats, Corin A.; Abudahab, Khalil; Underwood, Anthony; Bluemel, Benjamin; Aanensen, David M.; Unemo, Magnus; Pleininger, Sonja; Indra, Alexander; De Baetselier, Irith; Vanden Berghe, Wim; Hunjak, Blaženka; Blažić, Tatjana Nemeth; Maikanti-Charalambous, Panayiota; Pieridou, Despo; Zákoucká, Hana; Žemličková, Helena; Hoffmann, Steen; Cowan, Susan; Schwartz, Lasse Jessen; Peetso, Rita; Epstein, Jevgenia; Viktorova, Jelena; Ndeikoundam, Ndeindo; Bercot, Beatrice; Bébéar, Cécile; Lot, Florence; Buder, Susanne; Jansen, Klaus; Miriagou, Vivi; Rigakos, Georgios; Raftopoulos, Vasilios; Balla, Eszter; Dudás, Mária; Ásmundsdóttir, Lena Rós; Sigmundsdóttir, Guðrún; Hauksdóttir, Guðrún Svanborg; Gudnason, Thorolfur; Colgan, Aoife; Crowley, Brendan; Saab, Sinéad; Stefanelli, Paola; Carannante, Anna; Parodi, Patrizia; Pakarna, Gatis; Nikiforova, Raina; Bormane, Antra; Dimina, Elina; Perrin, Monique; Abdelrahman, Tamir; Mossong, Joël; Schmit, Jean-Claude; Mühlschlegel, Friedrich; Barbara, Christopher; Mifsud, Francesca; Van Dam, Alje; Van Benthem, Birgit; Visser, Maartje; Linde, Ineke; Kløvstad, Hilde; Caugant, Dominique; Młynarczyk-Bonikowska, Beata; Azevedo, Jacinta; Borrego, Maria-José; Nascimento, Marina Lurdes Ramos; Pavlik, Peter; Klavs, Irena; Murnik, Andreja; Jeverica, Samo; Kustec, Tanja; Vázquez Moreno, Julio; Diaz, Asuncion; Abad, Raquel; Velicko, Inga; Unemo, Magnus; Fifer, Helen; Shepherd, Jill; Patterson, LynseyBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.
- Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic surveyPublication . Harris, Simon R.; Cole, Michelle J.; Spiteri, Gianfranco; Sánchez-Busó, Leonor; Golparian, Daniel; Jacobsson, Susanne; Goater, Richard; Abudahab, Khalil; Yeats, Corin A.; Bercot, Beatrice; Borrego, Maria José; Crowley, Brendan; Stefanelli, Paola; Tripodo, Francesco; Abad, Raquel; Aanensen, David M.; Unemo, Magnus; Euro-GASP study groupBackground: Traditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data. Methods: We carried out an observational study, in which we sequenced isolates taken from patients with gonorrhoea from the European Gonococcal Antimicrobial Surveillance Programme in 20 countries from September to November, 2013. We also developed a web platform that we used for automated antimicrobial resistance prediction, molecular typing (N gonorrhoeae multi-antigen sequence typing [NG-MAST] and multilocus sequence typing), and phylogenetic clustering in conjunction with epidemiological and phenotypic data. Findings: The multidrug-resistant NG-MAST genogroup G1407 was predominant and accounted for the most cephalosporin resistance, but the prevalence of this genogroup decreased from 248 (23%) of 1066 isolates in a previous study from 2009–10 to 174 (17%) of 1054 isolates in this survey in 2013. This genogroup previously showed an association with men who have sex with men, but changed to an association with heterosexual people (odds ratio=4·29). WGS provided substantially improved resolution and accuracy over NG-MAST and multilocus sequence typing, predicted antimicrobial resistance relatively well, and identified discrepant isolates, mixed infections or contaminants, and multidrug-resistant clades linked to risk groups. Interpretation: To our knowledge, we provide the first use of joint analysis of WGS and epidemiological data in an international programme for regional surveillance of sexually transmitted infections. WGS provided enhanced understanding of the distribution of antimicrobial resistance clones, including replacement with clones that were more susceptible to antimicrobials, in several risk groups nationally and regionally. We provide a framework for genomic surveillance of gonococci through standardised sampling, use of WGS, and a shared information architecture for interpretation and dissemination by use of open access software.
- Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019Publication . Day, Michaela J.; Jacobsson, Susanne; Spiteri, Gianfranco; Kulishev, Carina; Sajedi, Noshin; Woodford, Neil; Blumel, Benjamin; van der Werf, Marieke J.; Amato-Gauci, Andrew J.; Unemo, Magnus; Cole, Michelle J.; Eder, Claudia; Pleininger, Sonja; Huhlescu, Steliana; de Baetselier, Irith; Hunjak, Blaženka; Blažić, Tatjana Nemeth; Maikanti-Charalampous, Panagiota; Pieridou, Despo; Zákoucká, Hana; Žemličková, Helena; Hoffmann, Steen; Cowan, Susan; Peetso, Rita; Viktorova, Jelena; Ndeikoundam, Ndeindo; Bercot, Beatrice; Sampo, Anu Patari; Kirjavainen, Vesa; Buder, Susanne; Jansen, Klaus; Miriagou, Vivi; Balla, Eszter; Dudás, Mária; Sigmundsdóttir, Guðrún; Asmundsdottir, Lena Ros; Saab, Sinead; Crowley, Brendan; Carannante, Anna; Stefanelli, Paola; Pakarna, Gatis; Mavcutko, Violeta; Cassar, Robert; Barbara, Christopher; Vella, Francesca; Van Dam, Alje; Linde, Ineke; Caugant, Dominique; Kløvstad, Hilde; Mlynarczyk-Bonikowska, Beata; Borrego, Maria-José; Pavlik, Peter; Klavs, Irena; Kustec, Tanja; Vazquez, Julio; Diaz, Asuncion; Torreblanca, Raquel Abad; Velicko, Inga; Unemo, Magnus; Fifer, Helen; Templeton, KateBackground: 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.