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Is previous azithromycin treatment associated with azithromycin resistance in Neisseria gonorrhoeae? A cross-sectional study using national surveillance data in England
  1. Soazig Clifton1,
  2. Katy Town2,
  3. Martina Furegato2,
  4. Michelle Cole2,
  5. Hamish Mohammed2,
  6. Sarah C Woodhall2,
  7. J Kevin Dunbar2,
  8. Helen Fifer2,
  9. Gwenda Hughes2
    1. 1 Centre for Population Research in Sexual Health and HIV, Institute for Global Health, University College London, London, UK
    2. 2 National Infection Service, Public Health England, London, UK
    1. Correspondence to Soazig Clifton, Centre for Population Research in Sexual Health and HIV, Institute for Global Health, University College London, London WC1E 6BT, UK; S.Clifton{at}


    Objectives It has been suggested that treatment of STIs with azithromycin may facilitate development of azithromycin resistance in Neisseria gonorrhoeae (NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectal Chlamydia trachomatis (CT), non-gonococcal urethritis (NGU) or NG (proxies for azithromycin exposure) in sexual health (GUM) services was associated with susceptibility of NG to azithromycin.

    Methods Azithromycin susceptibility data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2013–2015, n=4606) and additional high-level azithromycin-resistant isolates (HL-AziR) identified by the Public Health England reference laboratory (2013–2016, n=54) were matched to electronic patient records in the national GUMCAD STI surveillance dataset (2012–2016). Descriptive and regression analyses were conducted to examine associations between history of previous CT/NGU/NG and subsequent susceptibility of NG to azithromycin.

    Results Modal azithromycin minimum inhibitory concentration (MIC) was 0.25 mg/L (one dilution below the resistance breakpoint) in those with and without history of previous CT/NGU/NG (previous 1 month/6 months). There were no differences in MIC distribution by history of CT/NGU (P=0.98) or NG (P=0.85) in the previous 1 month/6 months or in the odds of having an elevated azithromycin MIC (>0.25 mg/L) (Adjusted OR for CT/NGU 0.97 (95% CI 0.76 to 1.25); adjusted OR for NG 0.82 (95% CI: 0.65 to 1.04)) compared with those with no CT/NGU/NG in the previous 6 months. Among patients with HL-AziR NG, 3 (4%) were treated for CT/NGU and 2 (3%) for NG in the previous 6 months, compared with 6% and 8%, respectively for all GRASP patients.

    Conclusions We found no evidence of an association between previous treatment for CT/NGU or NG in GUM services and subsequent presentation with an azithromycin-resistant strain. As many CT diagnoses occur in non-GUM settings, further research is needed to determine whether azithromycin-resistant NG is associated with azithromycin exposure in other settings and for other conditions.

    • antimicrobial resistance
    • neisseria gonorrhoea
    • azithromycin
    • surveillance

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    • Handling editor Khalil G Ghanem

    • Contributors This paper was conceived by HF, GH, KT and MF. SC conducted all data management and statistical analyses, with support from KT and MF. SC wrote the first draft of the article, with further contributions from KT, MF, MC, HM, SW, JKD, HF and GH. All authors interpreted data, reviewed successive drafts and approved the final version of the article.

    • Funding GRASP has been funded totally (2000–2004) and partly (2005–2010) by the Department of Health (England) and by Public Health England. SC was funded to undertake independent research supported by the National Institute for Health Research (NIHR Research Methods Programme, Fellowships and Internships, NIHR-RMFI-2014-05-28).

    • Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

    • Competing interests HF is on the Scientific Advisory Board for Discuva Ltd. The other authors have no competing interests to declare.

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

    • Data sharing statement Data sharing is per PHE HIV/STI department data sharing guidance (

    • Collaborators GRASP Steering Group: DM Livermore, C Bignell, H Donaldson, B Macrae, K Templeton, J Shepherd, P French, M Portman , AP Johnson, J Paul, A Robinson, J Ross, J Wade, C Ison, G Hughes, K Town, N Woodford, R Mulla, T Sadiq, H Fifer, A Andreasen, M Cole. Collaborating centres: Birmingham (M David, J Ross), Bristol (O M Williams, P Horner), Brighton (M Cubbon, G Dean), Cambridge (N Brown, C Carne), Cardiff (R Howe, J Nicholls), Gloucester (P Moore, A DeBurgh-Thomas), Homerton (A Jepson, M Nathan), Kings (J Wade, C McDonald, M Brady), 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 (R Mulla, T Balachandran), Manchester (A Qamruddin, A Sukthankar), Newcastle (M Valappil, K N 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, M Portman, E Jungmann), Wolverhampton (D Dobie, A Tariq) and Woolwich (M Dall’Antonia, J Russell).