Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales.

OBJECTIVES: Treatment of Neisseria gonorrhoeae is threatened by the emergence of antimicrobial resistance. We analysed data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales to identify groups most at risk of reduced susceptibility to the currently recommended first-line therapy, ceftriaxone. METHODS: Data from GRASP between 2007 and 2013 on ceftriaxone susceptibility and strain types were analysed. Risk factors associated with isolates exhibiting a ceftriaxone minimum inhibitory concentration (MIC) of ≥0.015 mg/L (CTR ≥0.015 mg/L) were identified using logistic regression. RESULTS: One third of isolates from men who have sex with men (MSM) (1279/4203) and 9.9% from heterosexuals (458/4626) exhibited CTR ≥0.015 mg/L. Between 2007 and 2013, the modal MIC for isolates remained at 0.004 mg/L for MSM but increased from 0.002 to 0.004 mg/L for heterosexuals. Among MSM, CTR ≥0.015 mg/L was associated with Asian ethnicity (crude OR: 1.42; 95% CI 1.07 to 1.88) and previous gonorrhoea (1.34; 1.16 to 1.54). Among heterosexuals, CTR ≥0.015 mg/L was associated with older age (35+ years: 4.31; 3.34 to 5.55), ≥6 sexual partners (1.58; 1.01 to 2.44) and sex abroad (2.23; 1.71 to 2.91). CTR ≥0.015 mg/L was less likely in isolates from heterosexuals of black Caribbean or African ethnicity (0.29; 0.20 to 0.41, 0.66; 0.43 to 0.99), with a concurrent chlamydial infection (0.25; 0.19 to 0.34) or women (0.57; 0.46 to 0.71). Over 600 isolates (CTR ≥0.015 mg/L) were typed; the majority were in Genogroup 1407, containing sequence type 1407. CONCLUSIONS: The emergence and spread of gonorrhoea with reduced susceptibility to ceftriaxone seems a realistic prospect, most likely in those involved in 'rapid-transmission' or bridging sexual networks.

Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone.

Treatment of gonorrhoea is threatened by antimicrobial resistance, and decreased susceptibility and resistance to recommended therapies is emerging in Europe. Current associations between resistance and molecular type remain poorly understood. Gonococcal isolates (n=1,066) collected for the 2009 and 2010 European Gonococcal Antimicrobial Surveillance Programme were typed by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). A total of 406 sequence types (STs) were identified, 125 of which occurred in ≥two isolates. Seven major genogroups of closely related STs (varying by ≤1% at just one of the two target loci) were defined. Genogroup 1407 (G1407), observed in 20/21 countries and predominant in 13/21 countries, accounted for 23% of all isolates and was associated with decreased susceptibility to cefixime and resistance to ciprofloxacin and raised minimum inhibitory concentrations for ceftriaxone and azithromycin. Genogroup 225 (G225), associated with ciprofloxacin resistance, was observed in 10% of isolates from 19/21 countries. None of the other genogroups were associated with antimicrobial resistance. The predominance of a multidrug-resistant clone (G1407) in Europe is worrying given the recent reports of recommended third generation cephalosporins failing to treat infections with this clone. Identifying associations between ST and antimicrobial resistance aids the understanding of the dissemination of resistant clones within a population and could facilitate development of targeted intervention strategies.