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      Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018

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          Abstract

          We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.

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          ClonalFrameML: Efficient Inference of Recombination in Whole Bacterial Genomes

          Xavier Didelot, Daniel J Wilson (2015)
          Recombination is an important evolutionary force in bacteria, but it remains challenging to reconstruct the imports that occurred in the ancestry of a genomic sample. Here we present ClonalFrameML, which uses maximum likelihood inference to simultaneously detect recombination in bacterial genomes and account for it in phylogenetic reconstruction. ClonalFrameML can analyse hundreds of genomes in a matter of hours, and we demonstrate its usefulness on simulated and real datasets. We find evidence for recombination hotspots associated with mobile elements in Clostridium difficile ST6 and a previously undescribed 310kb chromosomal replacement in Staphylococcus aureus ST582. ClonalFrameML is freely available at http://clonalframeml.googlecode.com/.
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            Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone.

            Makoto OHNISHI, Daniel Golparian, Ken Shimuta … (2011)
            Recently, the first Neisseria gonorrhoeae strain (H041) that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, the last remaining option for empirical first-line treatment, was isolated. We performed a detailed characterization of H041, phenotypically and genetically, to confirm the finding, examine its antimicrobial resistance (AMR), and elucidate the resistance mechanisms. H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of ESC resistance determinants (penA, mtrR, penB, ponA, and pilQ). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants. H041 was assigned to serovar Bpyust, MLST sequence type (ST) ST7363, and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2 to 4 μg/ml, which is 4- to 8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new penA mosaic allele caused the ceftriaxone resistance. In conclusion, N. gonorrhoeae has now shown its ability to also develop ceftriaxone resistance. Although the biological fitness of ceftriaxone resistance in N. gonorrhoeae remains unknown, N. gonorrhoeae may soon become a true superbug, causing untreatable gonorrhea. A reduction in the global gonorrhea burden by enhanced disease control activities, combined with wider strategies for general AMR control and enhanced understanding of the mechanisms of emergence and spread of AMR, which need to be monitored globally, and public health response plans for global (and national) perspectives are important. Ultimately, the development of new drugs for efficacious gonorrhea treatment is necessary.
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              High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure.

              Magnus Unemo, Daniel Golparian, Robert Nicholas … (2012)
              Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (penA, mtrR, penB, ponA, and pilQ). F89 was assigned to MLST sequence type 1901 (ST1901) and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC = 4 μg/ml) and ceftriaxone (MIC = 1 to 2 μg/ml) and resistance to most other antimicrobials examined. A novel penA mosaic allele (penA-CI), which was penA-XXXIV with an additional A501P alteration in penicillin-binding protein 2, was the primary determinant for high-level ESC resistance, as determined by transformation into a set of recipient strains. N. gonorrhoeae appears to be emerging as a superbug, and in certain circumstances and settings, gonorrhea may become untreatable. Investigations of the biological fitness and enhanced understanding and monitoring of the ESC-resistant clones and their international transmission are required. Enhanced disease control activities, antimicrobial resistance control and surveillance worldwide, and public health response plans for global (and national) perspectives are also crucial. Nevertheless, new treatment strategies and/or drugs and, ideally, a vaccine are essential to develop for efficacious gonorrhea management.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Euro Surveill
                Journal ID (iso-abbrev): Euro Surveill
                Journal ID (publisher-id): eurosurveillance
                Title: Eurosurveillance
                Publisher: European Centre for Disease Prevention and Control (ECDC)
                ISSN (Print): 1025-496X
                ISSN (Electronic): 1560-7917
                Publication date (Print): 07 March 2019
                Volume: 24
                Issue: 10
                Electronic Location Identifier: 1900147
                Affiliations
                [1 ]Big Data Institute, University of Oxford, Oxford, United Kingdom
                [2 ]Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
                [3 ]National Incident Management Team, Public Health England, London, United Kingdom
                [4 ]Population Health Sciences, University of Bristol, Bristol, United Kingdom
                [5 ]These authors contributed equally to this work
                Author notes

                Correspondence: David W Eyre ( david.eyre@ 123456bdi.ox.ac.uk )

                Author information
                http://orcid.org/0000-0001-5095-6367
                Article
                Publisher ID: 1900147 Publisher ID: 1900147
                DOI: 10.2807/1560-7917.ES.2019.24.10.1900147
                PMC ID: 6415501
                PubMed ID: 30862336
                SO-VID: 1f5bbd1a-cd6f-42e6-bf83-4e63fcd39bf3
                Copyright © This article is copyright of the authors or their affiliated institutions, 2019.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) Licence. You may share and adapt the material, but must give appropriate credit to the source, provide a link to the licence, and indicate if changes were made.

                History
                Date received : 22 February 2019
                Date accepted : 06 March 2019
                Categories
                Subject: Rapid Communication
                Custom metadata
                sequence 1

                Keywords: gonorrhoeae,treatment failure,antimicrobial resistance,antimicrobial treatment,whole-genome sequencing
                Data availability:
                Keywords: gonorrhoeae, treatment failure, antimicrobial resistance, antimicrobial treatment, whole-genome sequencing

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