Are sex norms the norm in gonococcal surveillance?
Authors: C R Robert George, Ratan L Kundu, David M Whiley, Monica M Lahra
Journal: The Lancet Microbe (2020)

Therapeutic guidelines and public health strategies for controlling Neisseria gonorrhoeae rely heavily on antimicrobial resistance (AMR) surveillance data.1Wi T Lahra MM Ndowa F et al.Antimicrobial resistance in Neisseria gonorrhoeae: global surveillance and a call for international collaborative action.PLoS Med. 2017; 14e1002344Crossref PubMed Scopus (287) Google Scholar, 2George CRR Enriquez RP Gatus BJ et al.Systematic review and survey of Neisseria gonorrhoeae ceftriaxone and azithromycin susceptibility data in the Asia Pacific, 2011 to 2016.PLoS One. 2019; 14e0213312Crossref PubMed Scopus (13) Google Scholar, 3Lahra MM Ward A Trembizki E et al.Treatment guidelines after an outbreak of azithromycin-resistant Neisseria gonorrhoeae in South Australia.Lancet Infect Dis. 2017; 17: 133-134Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar Historically, many international AMR surveillance reports have collected AMR data exclusively from males.4Kidd S Moore PC Kirkcaldy RD et al.Comparison of antimicrobial susceptibility of urogenital Neisseria gonorrhoeae isolates obtained from women and men.Sex Transm Dis. 2015; 42: 434-439Crossref PubMed Scopus (7) Google Scholar, 5Weston EJ Wi T Papp J Strengthening global surveillance for antimicrobial drug-resistant Neisseria gonorrhoeae through the enhanced gonococcal antimicrobial surveillance program.Emerg Infect Dis. 2017; 23: S47-S52Google Scholar, 6Latif AS Gwanzura L Machiha A et al.Antimicrobial susceptibility in Neisseria gonorrhoeae isolates from five sentinel surveillance sites in Zimbabwe, 2015-2016.Sex Transm Infect. 2018; 94: 62-66Crossref PubMed Scopus (8) Google Scholar, 7Bazzo ML Golfetto L Gaspar PC et al.First nationwide antimicrobial susceptibility surveillance for Neisseria gonorrhoeae in Brazil, 2015–16.J Antimicrob Chemother. 2018; 73: 1854-1861Crossref PubMed Scopus (20) Google Scholar, 8Hamasuna R Yasuda M Ishikawa K et al.The second nationwide surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae from male urethritis in Japan, 2012–2013.J Infect Chemother. 2015; 21: 340-345Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 9Nacht C Agingu W Otieno F Odhiambo F Mehta SD Antimicrobial resistance patterns in Neisseria gonorrhoeae among male clients of a sexually transmitted infections clinic in Kisumu, Kenya.Int J STD AIDS. 2020; 31: 46-52Crossref PubMed Scopus (1) Google Scholar Given the data suggesting that N gonorrhoeae clones circulating in men who have sex with men versus heterosexual populations potentially differ,10Town K Bolt H Croxford S et al.Neisseria gonorrhoeae molecular typing for understanding sexual networks and antimicrobial resistance transmission: a systematic review.J Infect. 2018; 76: 507-514Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar we investigated differences in susceptibility based on sex. Surveillance of a cohort of 14 312 gonococcal clinical isolates from New South Wales, Australia, derived from the Australian Gonococcal Surveillance Programme from 2015 to 2019 were analysed. The statistical program R (version 3.5.3; packages DescTools 0.99.31, ggplot2 3.2.1, Rmisc 1.5) was used to establish whether the gonococcal AMR profiles of male versus female populations differ. The endpoints of interest were proportional resistance for penicillin (minimum inhibitory concentration [MIC] ≥0·75 mg/L), ciprofloxacin (MIC ≥0·75 mg/L), azithromycin (MIC ≥0·75 mg/L), or proportional decreased susceptibility for ceftriaxone (MIC ≥0·047 mg/L). Binomial proportion CIs (95% CI; 5% significance level) were calculated by means of the Clopper–Pearson statistic, and annual totals, a 3-year moving window, and the cumulative multiannual total were plotted. Significant differences in proportional resistance and proportional decreased susceptibility were identified from gonococcal isolates derived from males versus females for all antimicrobial classes assessed (appendix). For both penicillin and ciprofloxacin, resistance was predominantly higher in females versus males, with cumulative proportional resistance in females 1·35 times higher for penicillin (proportional resistance 36·6% for females vs 27·1% for males); and 1·2 times higher for ciprofloxacin (proportional resistance 32·6% for females vs 27·1% for males). Conversely, for azithromycin, proportional resistance was 1·7 times higher in males versus females (proportional resistance 7·0% for males vs 4·1% for females). Regarding ceftriaxone, lower case numbers probably prevented separation of CIs for specific years. However, the potential for significant differences in ceftriaxone decreased susceptibility between males and females is shown with the 3-year moving window from 2016 to 2019, which shows significantly higher proportional decreased susceptibility in females versus males (1·8 times; proportional decreased susceptibility 2·4% for females vs 1·3% for males). In this large cohort analysis, we showed that AMR in Neisseria gonorrhoeae is frequently significantly different between male and female populations. The difference probably reflects differences in circulating strains in males versus females. The analysis suggests that surveillance systems that exclude gonococcal AMR data from females will misrepresent overall rates of AMR, and this poses risks in terms of optimal management of antibiotic resources. In this era of multiply and extensively drug-resistant Neisseria gonorrhoeae, optimising surveillance to inform guidelines, and for similar situation analysis, must be considered an operational imperative. This is part of the work of the National Neisseria Network, Australia. The National Neisseria Network and its programmes are funded by the Australian Government Department of Health. CRRG, RLK, and MML report no competing interests. DMW reports research funding from SpeeDx unrelated to the current study. Download .pdf (.18 MB) Help with pdf files Supplementary appendix