High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure

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Published in	Antimicrobial Agents and Chemotherapy Vol. 56; no. 3; pp. 1273 - 1280
Main Authors	Unemo, Magnus, Golparian, Daniel, Nicholas, Robert, Ohnishi, Makoto, Gallay, Anne, Sednaoui, Patrice
Format	Journal Article
Language	English
Published	Washington, DC American Society for Microbiology 01.03.2012
Subjects	Alleles Amino Acid Sequence Anti-Bacterial Agents Anti-Bacterial Agents - administration & dosage Antibiotics. Antiinfectious agents. Antiparasitic agents Bacterial diseases Bacterial diseases of the genital system Biological and medical sciences Biomarkers - analysis Cefixime Cefixime - administration & dosage Ceftriaxone Ceftriaxone - administration & dosage Cephalosporin Resistance Cephalosporin Resistance - drug effects Cephalosporin Resistance - genetics Epidemiology. Vaccinations France General aspects Gonorrhea Gonorrhea - drug therapy Gonorrhea - microbiology Human bacterial diseases Humans Infectious diseases Male Mechanisms of Resistance Medical sciences Microbial Sensitivity Tests Middle Aged Molecular Sequence Data Mosaicism Multilocus Sequence Typing Neisseria gonorrhoeae Neisseria gonorrhoeae - drug effects Neisseria gonorrhoeae - genetics Neisseria gonorrhoeae - isolation & purification Pharmacology. Drug treatments Population Surveillance Porins - analysis Porins - genetics Treatment Failure France Europe Clonality β-Lactams Neisseriaceae Ceftriaxone Infection Resistance Cephalosporin derivatives Allele Antibiotic Sexually transmitted disease Gonococcal infection Neisseria gonorrhoeae Treatment Bacteriosis Bacteria Micrococcales Genetics Mosaicism Antibacterial agent Cefixime Failure Clone International
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Abstract	Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: AAC
AbstractList	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. Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: AAC 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. 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.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.
Author	Robert Nicholas Anne Gallay Makoto Ohnishi Magnus Unemo Daniel Golparian Patrice Sednaoui
Author_xml	– sequence: 1 givenname: Magnus surname: Unemo fullname: Unemo, Magnus organization: WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden – sequence: 2 givenname: Daniel surname: Golparian fullname: Golparian, Daniel organization: WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden – sequence: 3 givenname: Robert surname: Nicholas fullname: Nicholas, Robert organization: Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA – sequence: 4 givenname: Makoto surname: Ohnishi fullname: Ohnishi, Makoto organization: National Institute of Infectious Diseases, Tokyo, Japan – sequence: 5 givenname: Anne surname: Gallay fullname: Gallay, Anne organization: Institut de Veille Sanitaire, Saint-Maurice, France – sequence: 6 givenname: Patrice surname: Sednaoui fullname: Sednaoui, Patrice organization: Institut Alfred Fournier, Centre National de Référence des Gonocoques, Paris, France
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25557366$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22155830$$D View this record in MEDLINE/PubMed
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Snippet	Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit... Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the... Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the...
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SubjectTerms	Alleles Amino Acid Sequence Anti-Bacterial Agents Anti-Bacterial Agents - administration & dosage Antibiotics. Antiinfectious agents. Antiparasitic agents Bacterial diseases Bacterial diseases of the genital system Biological and medical sciences Biomarkers - analysis Cefixime Cefixime - administration & dosage Ceftriaxone Ceftriaxone - administration & dosage Cephalosporin Resistance Cephalosporin Resistance - drug effects Cephalosporin Resistance - genetics Epidemiology. Vaccinations France General aspects Gonorrhea Gonorrhea - drug therapy Gonorrhea - microbiology Human bacterial diseases Humans Infectious diseases Male Mechanisms of Resistance Medical sciences Microbial Sensitivity Tests Middle Aged Molecular Sequence Data Mosaicism Multilocus Sequence Typing Neisseria gonorrhoeae Neisseria gonorrhoeae - drug effects Neisseria gonorrhoeae - genetics Neisseria gonorrhoeae - isolation & purification Pharmacology. Drug treatments Population Surveillance Porins - analysis Porins - genetics Treatment Failure
Title	High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure
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