title: Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000-2013.
abstract: Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance mechanisms.
  
  
  
  We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project.
  
  
  
  Reduced extended-spectrum cephalosporin susceptibility is predominantly clonal and associated with the mosaic penA XXXIV allele and derivatives (sensitivity 98% for cefixime and 91% for ceftriaxone), but alternative resistance mechanisms have sporadically emerged. Reduced azithromycin susceptibility has arisen through multiple mechanisms and shows limited clonal spread; the basis for resistance in 36% of isolates with reduced azithromycin susceptibility is unclear. Quinolone-resistant N. gonorrhoeae has arisen multiple times, with extensive clonal spread.
  
  
  
  Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance. The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea.
authors.affiliation: Department of Immunology and Infectious Diseases.|Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School.
authors.forename: Yonatan H
authors.initials: YH
authors.lastname: Grad
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Kirkcaldy
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Green
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Debora S
authors.initials: DS
authors.lastname: Marks
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton.|Department of Medicine, University of Cambridge and Addenbrookes Hospital, Cambridge, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: David
authors.initials: D
authors.lastname: Trees
authors.affiliation: Department of Immunology and Infectious Diseases.|Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005798:Genes, Bacterial; D023281:Genomics; D006069:Gonorrhea / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015995:Prevalence; D014481:United States / Q000453:epidemiology; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D018942:Macrolides
keywords: Neisseria gonorrhoeae; antibiotic resistance; cephalosporins; fluoroquinolones; genomic epidemiology; gonorrhea; macrolides; molecular diagnostics