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Original article
Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales
  1. K Town1,
  2. C Obi1,
  3. N Quaye2,
  4. S Chisholm2,
  5. G Hughes1
  6. on behalf of the GRASP Collaborative Group
    1. 1HIV/STI Department, National Infection Service, Public Health England, London, UK
    2. 2Sexually Transmitted Bacteria Reference Unit, National Infection Service, Public Health England, London, UK
    1. Correspondence to K Town, HIV/STI Department, National Infection Service, Public Health England, PHE Colindale, 61 Colindale Avenue, London NW9 5EQ, UK; Katy.town{at}phe.gov.uk

    Abstract

    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.

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    Footnotes

    • Handling editor Jackie A Cassell

    • Collaborators The GRASP collaborative steering group (DM Livermore, C Bignell, K Eastick, A Johnson, J Paul, A Robinson, J Ross, J Wade, C Ison, N Woodford, R Mulla, T Sadiq, H Fifer, A Andreasen) and the collaborating centers—Birmingham (M David, J Ross), Bristol (OM Williams, P Horner), Brighton (M Cubbon, G Dean), Cambridge (N Brown, C Carne), Cardiff (R Howe, R Drayton), Gloucester (P Moore, A DeBurgh-Thomas), Homerton (A Jepson, M Nathan), Kings (J Wade, M Tenant-Flowers), Leeds (M Denton, J Clarke), Liverpool (J Anson, M Bradley), London Charing Cross, Chelsea and Westminster (K McLean, A McOwan, G Paul, H Donaldson), Luton ( T Balachandran), Manchester (A Qamruddin, A Sukthankar), Newcastle (M Valappil, KN Sankar), Newport (S Majumdar, H Birley), Northampton (M Minassian, L Riddell), Nottingham (V Weston, C Bignell, M Pammi), Reading (G Wildman, S Iyer), Sheffield (L Prtak, C Bowman, C Dewnsap), St George's (P Riley, P Hay), St Mary's (D Wilkinson), University College Hospital (B Macrae, A Robinson, E Jungmann), Wolverhampton (D Dobie, A Tariq) and Woolwich (M Dall'Antonia, J Russell). GRASP has been funded totally (2000–2004) and partly (2005–2010) by the Department of Health (England) and by Public Health England.

    • Contributors KT, SC and GH collaborated in the writing of the manuscript. CO and NQ reviewed drafts. KT, SC, GH and CO were involved in the design of the study. KT conducted all analyses. CO collected clinical data and completed preliminary analyses. NQ and SC conducted MIC testing on samples.

    • Funding GRASP and authors of this study are funded by Public Health England.

    • Competing interests GH is a STI surveillance consultant for the Swiss government and has received grants for the National Institute of Health Research (NIHR) for Health Protection Research Units and also from NIHR for the Health Technologies Assessment Programme. SC has received grants from the European Centre for Disease Prevention and Control for the European Network for STI Microbiology and also a grant from the NIHR for a randomised controlled trial to compare the clinical effectiveness and safety of gentamicin and ceftriaxone in the treatment of gonorrhoea. In addition, SC was involved in small evaluations of other/novel antimicrobial compounds conducted for the following companies who provided funds to cover costs: Merck, Wockhardt Ltd and PTC Therapeutics.

    • Ethics approval Public Health England has permission to handle data obtained by GRASP under section 251 of the UK National Health Service Act of 2006 (previously section 60 of the Health and Social Care Act of 2001), which was renewed annually by the ethics and confidentiality committee of the National Information Governance Board (now the HRA Confidentiality Advisory Group).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data sharing is per PHE HIV/STI department data sharing guidance (https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/423828/20150424_PHE_HIV_STI_Data_Sharing_Policy_v4.1.pdf).

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