title: Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011.
abstract: BACKGROUND
  Effective treatment of gonorrhoea is fundamental to public health control; however, the ability of Neisseria gonorrhoeae to successively develop resistance to different treatments has hampered control efforts. The extended-spectrum cephalosporins--cefixime and ceftriaxone--have been recommended in the UK for treatment of gonorrhoea since 2005. We looked at surveillance data from England and Wales to ascertain the current usefulness of these drugs and to inform changes to national treatment guidelines.
  
  
  METHODS
  We obtained data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) for patients attending 26 genitourinary medicine clinics in England and Wales between 2007 and 2011. We did analyses with univariate and multivariable logistic regression methods to identify trends in susceptibility to cephalosporins and risk factors associated with infection with isolates with decreased susceptibility to cefixime, and we assessed changes in prescribing practices. We did molecular typing to investigate genetic relatedness of non-susceptible isolates.
  
  
  RESULTS
  The prevalence of decreased susceptibility to both cefixime and ceftriaxone rose between 2007 and 2010 but was more noticeable for cefixime (an increase from 1·5% in 2007 to 17·1% in 2010), with a bimodal distribution of minimum inhibitory concentration recorded between 2009 and 2010. By multivariable analysis, isolates with decreased susceptibility to cefixime were associated with infection in men who have sex with men (odds ratio 5·47, 95% CI 3·99-7·48; p<0·0001) and year of isolation (in 2010, 13·08, 7·49-22·8; p<0·0001). Such isolates had a largely clonal population, with most belonging to genogroup G1407 and harbouring the penA mosaic gene. Data from 2011 showed a significant decline in prevalence of isolates with decreased cefixime susceptibility, falling from 17·1% in 2010 to 10·8% in 2011 (p<0·0001), concomitant with the change in prescribing practice in 2010 from cefixime to ceftriaxone plus azithromycin.
  
  
  CONCLUSIONS
  Guidance for treatment of gonorrhoea in England and Wales was changed in 2010 to prolong the use of cephalosporins. The decline in prevalence of isolates with decreased cefixime susceptibility cannot be attributed unequivocally to this change in prescribing practice; however, the association is striking.
  
  
  BACKGROUND
  Department of Health (England), Public Health England.
authors.affiliation: Sexually Transmitted Bacteria Reference Unit, Microbiological Services, Public Health England, London, UK. Catherine.Ison@phe.gov.uk
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Ison
authors.forename: Katy
authors.initials: K
authors.lastname: Town
authors.forename: Chinelo
authors.initials: C
authors.lastname: Obi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chisholm
authors.forename: Gwenda
authors.initials: G
authors.lastname: Hughes
authors.forename: David M
authors.initials: DM
authors.lastname: Livermore
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Lowndes
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020682:Cefixime / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004739:England / Q000453:epidemiology; D005260:Female; D005798:Genes, Bacterial; D006069:Gonorrhea / Q000453:epidemiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D018272:Porins / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D012725:Sexual Behavior; D014852:Wales / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018272:Porins; C057699:porin protein, Neisseria; D002443:Ceftriaxone; D020682:Cefixime