Prevalence of cefixime-resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021-2022.

While ceftriaxone remains the first-line treatment for gonorrhoea, the US CDC recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021-2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176) and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was the highest among women (16.4%, 10/61), followed by men-who-have-sex-with-women (6.4%, 7/109), and men-who-have-sex-with-men (5.8%, 57/982). The prevalence of cefixime-resistant N. gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; and thus, cefixime treatment would have limited benefits in Australia.

Using crowdsourcing at an academic conference to develop STI testing messaging for public dissemination.

OBJECTIVES: We provide a guide to conducting a crowdsourcing activity at an international sexually transmitted infection (STI) conference to design public messaging about STI testing and disseminating that messaging via social media. METHODS: A speaker gave a presentation at a conference plenary session on the concepts of cocreation, crowdsourcing and designathons, and the application of these participatory approaches in public health research. To illustrate one of these approaches (crowdsourcing), attendees in the audience were asked to take part in a voluntary participatory activity, in which they would pair up with a fellow attendee sitting nearby and write down an idea on a blank notecard. Dyads were given 10 min to create an entry responding to the prompt, 'Write something that inspires gonorrhoea and/or chlamydia testing (eg, picture, jingle, rhyme)'. Each entry was judged by at least four independent judges on a scale of 0 (lowest quality) to 10 (highest quality) based on their innovation and potential to promote chlamydia/gonorrhoea testing. Scores were averaged to determine the finalist entries. RESULTS: We received 32 entries. The average score was 6.41 and scores ranged from 4.5 to 8 (median 6.63, IQR 5.75, 7.06). Half of entries (n=16) were slogans, 15.6% (n=5) were poems/rhymes, 12.5% (n=4) were memes/images, 9.4% (n=3) were programme implementation ideas, 3.1% (n=1) was a song verse, and 3.1% (n=1) was a video idea. One finalist entry was a meme and received 720 impressions, 120 engagements, 27 detail expands, 19 likes, 6 reposts and 1 response on Twitter. The second finalist entry was a slogan and received 242 impressions, 16 engagements, 6 detail expands, 4 likes and 2 reposts. CONCLUSIONS: Conducting crowdsourcing activities at future conferences may be an innovative, feasible way to develop and disseminate engaging and important STI and other health messaging to the public in a short period of time.

Frequent chlamydia and gonorrhoea but very infrequent syphilis among men who have sex with men using HIV pre-exposure prophylaxis in West Africa.

OBJECTIVES: Although oral pre-exposure prophylaxis (PrEP) for HIV is being rolled out in West Africa, data on sexually transmitted infections (STIs) in PrEP users are scarce. We assessed the prevalence, incidence and determinants of bacterial STIs in men who have sex with men (MSM) taking PrEP in Burkina Faso, Côte d'Ivoire, Mali and Togo. METHODS: A prospective cohort study among MSM initiating PrEP as part of a comprehensive HIV prevention package was conducted between 2017 and 2021 in community-based clinics in the four study countries. Molecular screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was performed at months 0, 6 and 12. Serological testing for syphilis was performed every 3 months over the first year of follow-up. Determinants of CT and/or NG incidence were identified using Poisson generalised linear mixed models. RESULTS: A total of 598 participants with a median age of 24.7 years were included. Prevalence of CT and/or NG was 24.4% (95% CI 21.0 to 28.1), 22.4% (95% CI 18.4 to 26.8) and 29.0% (95% CI 24.2 to 34.1) at months 0, 6 and 12, respectively. The prevalence of syphilis ranged from 0.2% (95% CI 0.0 to 0.9) at month 0 to 0.8% (95% CI 0.2 to 2.4) at month 12. Ninety incident CT and/or NG infections occurred during a total follow-up time of 280.6 person-years (incidence rate 32.1 per 100 person-years, 95% CI 25.8 to 39.4). Three incident syphilis infections were detected during a total follow-up time of 459.7 person-years (incidence rate 0.7 per 100 person-years, 95% CI 0.1 to 1.9). CT and/or NG incidence was associated with condomless insertive anal sex (adjusted incidence rate ratio 1.96, 95% CI 1.04 to 3.71, p=0.038). CONCLUSIONS: CT and NG were frequent but syphilis was very infrequent in MSM using HIV PrEP in West Africa. HIV programme managers should integrate STI services into PrEP programmes.

Evaluating preanalytical sample storage parameters for nucleic acid-based detection of Neisseria gonorrhoeae.

OBJECTIVES: To ensure accurate diagnosis of infectious diseases, preanalytical factors should be considered when assessing specimen quality and subsequent test result. Accordingly, we aimed to systematically assess the effect of storage time, temperature and buffer on the analytical sensitivity of detecting the sexually transmitted pathogen, Neisseria gonorrhoeae across multiple molecular diagnostic platforms. METHODS: Cultured N. gonorrhoeae was spiked into generic and commercial storage buffers and stored at four temperatures and five time points, ranging from -20°C to 37°C, over 30 days. Samples were processed using the Alinity m STI, Xpert CT/NG and Aptima Combo 2 nucleic acid amplification assays and an in-house quantitative PCR assay. A reduction in analytical sensitivity was defined as a significant (p<0.05) increase in cycle threshold (Ct) value relative to control samples. RESULTS: In total, 2756 samples were processed, with N. gonorrhoeae detected in 99.2% of samples. With respect to time, analytical sensitivity was maintained from day 2 (113/120; 94.2%) up to day 30 (110/120; 91.7%) relative to baseline samples. With respect to temperature, analytical sensitivity was maintained from -20°C (147/150; 98.0%) up to 37°C (136/150; 90.7%) relative to baseline samples. Generic buffers, Viral Transport Medium and Amies Liquid Media showed a reduction in analytical sensitivity compared with their commercial counterparts, Aptima Multitest Swab Transport Media and Abbott Alinity transport buffer using select diagnostic assays; this reduction appeared temperature dependent, with the largest differences in median Ct values observed at 37°C (p<0.05). CONCLUSIONS: Increased prevalence of sample self-collection for sexually transmitted infections (STIs) warrants an evaluation of preanalytical sample storage variables on diagnostic testing performance. Here, across a range of time points, temperatures and storage buffers, N. gonorrhoeae was successfully detected, supporting flexibility in sample storage, and by extension the feasibility of analysing self-collected samples to improve access to STI testing.

Unnecessary antibiotic use in men who have sex with men (MSM) with anogenital symptoms attending a sexual health clinic: a retrospective analysis.

OBJECTIVES: To quantify the amount of unnecessary antibiotics, in particular ceftriaxone, given to men who have sex with men (MSM) with anogenital symptoms as part of presumptive management in an urban sexual health clinic and examine factors associated with unnecessary ceftriaxone. METHODS: This is a retrospective cross-sectional analysis of electronic records from all visits involving MSM reporting symptoms of bacterial sexually transmitted infection (STI) and who received presumptive antibiotics at Sydney Sexual Health Centre. The following variables were extracted: demographic and sexual behaviour data, presenting symptoms, prior STI diagnoses, use of anoscopy, use of point-of-care microscopy, prescriptions of antibiotics and subsequent nucleic acid amplification testing (NAAT) results for chlamydia and gonorrhoea in all anatomical sites (urethra, pharynx and rectum). We defined unnecessary antibiotic as an agent prescribed to treat an STI organism that was subsequently not detected. RESULTS: Among 1061 visits in this analysis, 41.8% yielded negative NAAT results for both chlamydia and gonorrhoea in all anatomical sites. There were 44.3% of visits which had positive gonorrhoea NAAT result in at least one anatomical site. There were 187 courses of ceftriaxone prescribed in patients who tested negative for gonorrhoea in all anatomical sites and therefore were unnecessary. Unnecessary ceftriaxone prescribing occurred in 50.2% of visits with anorectal symptoms, 19.6% of scrotal symptoms and 7.3% of urethral symptoms. Microscopy was associated with significantly less unnecessary ceftriaxone in urethral but not anorectal or scrotal presentations. In multivariable analysis, the following factors were associated with a higher likelihood of unnecessary ceftriaxone use: anorectal symptoms, scrotal symptoms, gonorrhoea in the preceding year, contact of a bacterial STI and living with HIV. CONCLUSIONS: This study highlights the significant amount of unnecessary ceftriaxone used for STI symptoms in MSM. A new pathway incorporating rapid point-of-care molecular testing in symptomatic patients may improve the precision of antibiotic prescribing and reduce unnecessary use.

In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides.

PURPOSE: Single doses of gentamicin have demonstrated clinical efficacy in the treatment of urogenital gonorrhea, but lower cure rates for oropharyngeal and anorectal gonorrhea. Formulations selectively enriched in specific gentamicin C congeners have been proposed as a less toxic alternative to gentamicin, potentially permitting higher dosing to result in increased plasma exposures at the extragenital sites of infection. The purpose of the present study was to compare the antibacterial activity of individual gentamicin C congeners against Neisseria gonorrhoeae to that of other aminoglycoside antibiotics. METHODS: Antimicrobial susceptibility of three N. gonorrhoeae reference strains and 152 clinical isolates was assessed using standard disk diffusion, agar dilution, and epsilometer tests. RESULTS: Gentamicin C1, C2, C1a, and C2a demonstrated similar activity against N. gonorrhoeae. Interestingly, susceptibility to the 1-N-ethylated aminoglycosides etimicin and netilmicin was significantly higher than the susceptibility to their parent compounds gentamicin C1a and sisomicin, and to any other of the 25 aminoglycosides assessed in this study. Propylamycin, a 4'-propylated paromomycin analogue, was significantly more active against N. gonorrhoeae than its parent compound, too. CONCLUSION: Selectively enriched gentamicin formulations hold promise for a less toxic but equally efficacious alternative to gentamicin. Our study warrants additional consideration of the clinically established netilmicin and etimicin for treatment of genital and perhaps extragenital gonorrhea. Additional studies are required to elucidate the mechanism behind the advantage of alkylated aminoglycosides.

45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

Epidemiology of gonorrhoea: systematic review, meta-analyses, and meta-regressions, World Health Organization European Region, 1949 to 2021.

BackgroundEpidemiology of Neisseria gonorrhoeae (NG) infection remains inadequately understood.AimWe aimed to characterise NG epidemiology in Europe.MethodsWe used Cochrane and PRISMA guidelines to systematically review, report, synthesise and analyse NG prevalence data from 1949 to 30 September 2021. Random-effects meta-analyses estimated pooled prevalence. Meta-regression analyses investigated associations and sources of heterogeneity.ResultsThe 844 included publications yielded 1,573 prevalence measures. Pooled prevalence of current urogenital infection was 1.0% (95% CI: 0.7-1.2%) among general populations, 3.2% (95% CI: 1.8-4.8%) among female sex workers, 4.9% (95% CI: 4.2-5.6%) among sexually transmitted infection clinic attendees and 12.1% (95% CI: 8.8-15.8%) among symptomatic men. Among men who have sex with men, pooled prevalence was 0.9% (95% CI: 0.5-1.4%), 5.6% (95% CI: 3.6-8.1%), and 3.8% (95% CI: 2.5-5.4%), respectively, for current urogenital, anorectal or oropharyngeal infection. Current urogenital, anorectal or oropharyngeal infection was 1.45-fold (95% CI: 1.19-1.77%), 2.75-fold (95% CI: 1.89-4.02%) and 2.64-fold (95% CI: 1.77-3.93%) higher among men than women. Current urogenital infection declined 0.97-fold (95% CI: 0.96-0.98%) yearly, but anorectal and oropharyngeal infection increased (1.02-fold; 95% CI: 1.01-1.04% and 1.02-fold; 95% CI: 1.00-1.04%), respectively.ConclusionsNeisseria gonorrhoeae epidemiology in Europe has distinct and contrasting epidemiologies for vaginal sex transmission in heterosexual sex networks vs anal and oral sex transmission in MSM sexual networks. Increased transmission may facilitate drug-resistant strain emergence. Europe is far from achieving the World Health Organization target of 90% incidence reduction by 2030.

Gonorrhoea on the rise in Denmark since 2022: distinct clones drive increase in heterosexual individuals.

A surge in gonorrhoea in Denmark has occurred since 2022, a 46% increase from 2021. National surveillance, leveraging mandatory reporting and epidemiological data, highlights three distinct clades linked to heterosexual transmission. Despite the rise, these exhibit high susceptibility, contrasting MSM-associated strains. Geographical hotspots and age-specific patterns further illuminate transmission dynamics. The combination of genomic and epidemiological data provides novel insights into the evolving landscape of gonorrhoea, indicating potential shifts in infection dynamics and transmissibility.

Sharp increase in gonorrhoea notifications among young people, EU/EEA, July 2022 to June 2023.

Gonorrhoea cases increased steeply in women aged 20 to 24 years across 15 EU/EEA countries in July to December 2022 and January to June 2023 with, respectively, 73% and 89% more cases reported than expected, based on historical data from 2015 to 2019. Smaller increases among men due to heterosexual transmission were observed in nine EU/EEA countries. Interventions to raise awareness among young people about sexually transmitted infection risks are needed, emphasising the benefit of safe sexual practices and testing.

Questioning risk compensation: pre-exposure prophylaxis (PrEP) and sexually transmitted infections among men who have sex with men, capital region of Denmark, 2019 to 2022.

BackgroundPre-exposure prophylaxis (PrEP) effectively prevents HIV, but its association with sexually transmitted infections (STIs) has raised concerns about risk compensation, potentially impacting the expansion of PrEP programmes.AimWe examined the relationship between PrEP and the incidence of chlamydia, gonorrhoea and syphilis.MethodsIn this prospective cohort study, we compared STI rates before and after PrEP initiation among users in the capital region of Denmark (2019-2022), calculating incidence rate ratios adjusted for age and testing frequency (aIRR). To pinpoint when increases began, we plotted weekly STI rates, adjusting the timeline to correspond with PrEP initiation.ResultsThe study included 1,326 PrEP users with a median age of 35 years. The STI incidence rate per 100,000 person-years rose from 35.3 before to 81.2 after PrEP start, with an aIRR of 1.35 (95% CI: 1.18-1.56). Notably, this increase preceded PrEP initiation by 10-20 weeks. Specific aIRR for chlamydia, gonorrhoea and syphilis were 1.23 (95% CI: 1.03-1.48), 1.24 (95% CI: 1.04-1.47) and 1.15 (95% CI: 0.76-1.72), respectively. In subanalyses for anatomical sites aIRR was 1.26 (95% CI: 1.01-1.56) for rectal chlamydia and 0.66 (95% CI: 0.45-0.96) for genital gonorrhoea.ConclusionWe found a 35% increase in STI incidence associated with PrEP use. It started before PrEP initiation, challenging the assumption that PrEP leads to risk compensation. Instead, the data suggest that individuals seek PrEP during periods of heightened sexual risk-taking. Consequently, PrEP programmes should include sexual health consultations, STI testing, treatment and prevention strategies to prevent HIV and improve sexual health.

Gonorrhoea in Poland in 2021. / Rzezaczka w Polsce w 2021 roku.

BACKGROUND: The incidence of gonorrhoea at the European level increased over 2012-2019, decreased in 2020, and then reached higher values in 2021 than in 2019. OBJECTIVE: Analysis in the descriptive epidemiology scheme of gonorrhoea notification in surveillance in Poland in 2021 (being the second year of the COVID-19 pandemic). MATERIAL AND METHODS: Case-base data from surveillance of gonorrhoea were used: confirmed case (meeting laboratory criteria), probable (meeting clinical criteria and contact with confirmed case) and possible (only in Poland - physician diagnosed gonorrhoea, no information available for proper classification). Statistic Poland data was used to calculate the indicators. Data on patients treated in dermatology-venereology clinics between 2019-2021 were taken from the Bulletins of the Ministry of Health. RESULTS: The incidence of gonorrhoea in Poland in 2021 was only a fraction of recorded in the EU/EEA (0.74 vs. 13.7/100000)-similar to the first pandemic year and were about half of those notified in the 2019 (the peak year; 281 vs. 522 cases). There were 15.5 men per one female (incidence: 1.6/100000 men, 0.1/100000 women). Every second case was among aged 25-34 (49.62%), every fourth-aged 35-44 (23.11%). Under 15, no cases were reported. The predominant site was the genitourinary (excluding missing data: 85.3%). The cases with missing information on transmision increased (49.1%; aged 45+: 72.0%, women: 76.5%). Delays in reporting data were identified (greater than in 2019, however, less than in 2020), ~17% cases were from 2019-2020. Dermatology-venerology clinics treated 385 people - less than in 2020, however, more than reported in epidemiological surveillance (vs. 281). CONCLUSIONS: The COVID-19 pandemic has influenced on the surveillance system in Poland. There are difficulties in interpreting the epidemiological trend. It is necessary to: 1) intensify systemic solutions in the area of prevention, including sexual partners; 2) raise the awareness of healthcare professionals and sanitary inspection workers on the role of collecting epidemiological information.

Characterization of outer membrane vesicles released by clinical isolates of Neisseria gonorrhoeae.

The sexually transmitted pathogen Neisseria gonorrhoeae releases membrane vesicles including outer membrane vesicles (OMVs) during infections. OMVs traffic outer membrane molecules, such as the porin PorB and lipo-oligosaccharide (LOS), into host innate immune cells, eliciting programmed cell death pathways, and inflammation. Little is known, however, about the proteome and LOS content of OMVs released by clinical strains isolated from different infection sites, and whether these vesicles similarly activate immune responses. Here, we characterized OMVs from four N. gonorrhoeae isolates and determined their size, abundance, proteome, LOS content, and activation of inflammatory responses in macrophages. The overall proteome of the OMVs was conserved between the four different isolates, which included major outer membrane and periplasm proteins. Despite this, we observed differences in the rate of OMV biogenesis and the relative abundance of membrane proteins and LOS. Consequently, OMVs from clinical isolates induced varying rates of macrophage cell death and the secretion of interleukin-1 family members, such as IL-1α and IL-1ß. Overall, these findings demonstrate that clinical isolates of N. gonorrhoeae utilize membrane vesicles to release proteins and lipids, which affects innate immune responses.

Prevalence of STIs and people's satisfaction in a general population STI testing site in Bern, Switzerland.

OBJECTIVES: Access to affordable STI testing for asymptomatic persons is important to reduce STI transmission. Our testing site offers easily accessible and affordable STI testing for the general population irrespective of symptoms. Here we report STI prevalence and motivational factors of attendance. METHODS: Between 2017 and 2019, all participants at our STI testing site at the University Hospital Bern, Switzerland, were interviewed with a computer-based self-completion questionnaire. Pooled (oral, genital and anal) swabs were tested for Chlamydia trachomatis, Neisseria gonorrhoeae and blood samples for syphilis and HIV. People's motivational factors to attend were assessed using a standardised questionnaire. RESULTS: 5402 individuals between 17 and 82 (median 33.5) years were included. Of those, 2550 (47.2%) were between 25 and 34 years old and 3133 were heterosexual (58%), with rising attendance over the years. One-third attended because of a new sexual relationship, and one-third reported condomless sex. Among all individuals, we found 191 (3.8%) new chlamydia infections (89/191 in females and 101/191 in males) and 54 (1.1%) gonorrhoea infections (44/54 in males). In addition, 52/5125 tested individuals (0.8%) had syphilis requiring treatment.The number of sexual partners, previous bacterial STIs and condomless sex were associated with having an STI. Four heterosexual individuals were newly diagnosed with HIV. People rated a low threshold offer (through online booking or telephone) and personal counselling as most important factors to attend the service. CONCLUSION: We found many asymptomatic bacterial STIs requiring treatment. Offering easily accessible STI testing and counselling proved successful as shown by increasing rates of attendance and high levels of satisfaction.

Dose selection for a phase III study evaluating gepotidacin (GSK2140944) in the treatment of uncomplicated urogenital gonorrhoea.

BACKGROUND: Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and is active against most strains of Neisseria gonorrhoeae (N. gonorrhoeae). Phase II data suggested higher exposures were needed for efficacy and to suppress resistance development. A translational approach using in vitro pharmacokinetic/pharmacodynamic (PK/PD) and clinical data was used to select a gepotidacin dose for a phase III study. In this narrative review of previously shown data, we summarise how a translational approach based on in vitro PK/PD and population PK modelling and simulation data was undertaken to select a dosing regimen for the ongoing phase III gepotidacin study in participants with uncomplicated urogenital gonorrhoea. METHODS: For dose selection, prior in vitro minimum inhibitory concentrations (MICs) and PK/PD data were available. PK modelling was conducted to determine a dose that would limit plasma concentrations to less than 14 µg/mL (as concentrations above this are associated with QT prolongation and effects associated with acetylcholinesterase inhibition) while maintaining ≥90% probability of target attainment (PTA) for efficacy and resistance suppression against N. gonorrhoeae isolates with gepotidacin MICs ≤1 µg/mL. RESULTS: Two 3000 mg gepotidacin doses, administered 10-12 hours apart, resulted in PTA of ≥97.5% and ≥91.7% for gepotidacin MICs ≤1 µg/mL for the ratio of the area under the free drug plasma concentration-time curve over 24 hours to the MIC (fAUC0-24/MIC) efficacy, and resistance suppression targets of 40 and 46, respectively, but limited the occurrence of maximum plasma concentrations ≥14 µg/mL. CONCLUSIONS: Two gepotidacin 3000 mg oral doses 10-12 hours apart provide ~2-fold higher systemic exposures, increase efficacy for higher gepotidacin MIC N. gonorrhoeae isolates, reduce resistance potential and limit plasma concentrations of potential safety concern, compared with higher doses.

Is there an association between previous infection with Neisseria gonorrhoeae and gonococcal AMR? A cross-sectional analysis of national and sentinel surveillance data in England, 2015-2019.

OBJECTIVES: Quarterly STI screening is recommended for high-risk gay, bisexual and other men who have sex with men (MSM) in the UK, but frequent antibiotic exposure could potentially increase the risk of antimicrobial resistance (AMR) developing in Neisseria gonorrhoeae. We investigated whether repeat diagnosis of gonorrhoea in those attending sexual health services (SHS) was associated with reduced antimicrobial susceptibility. METHODS: Antimicrobial susceptibility data relating to the most recent gonorrhoea diagnosis for each individual included in the Gonococcal Resistance to Antimicrobials Surveillance Programme (2015-2019) were matched to their historical records in the national GUMCAD STI surveillance data set (2012-2019). The number of gonorrhoea diagnoses in the previous 3 years was calculated for each SHS attendee. Logistic regression was used to examine the associations between the number of diagnoses and reduced susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) >0.03 mg/L), cefixime (MIC >0.06 mg/L) and azithromycin (MIC >0.25 mg/L) at the time of the latest diagnosis. RESULTS: Of 6161 individuals included in the analysis, 3913 (63.5%) were MSM, 1220 (19.8%) were heterosexual men and 814 (13.2%) were women. Among MSM, 2476 (63.3%) had 1 past gonorrhoea diagnosis, 1295 (33.1%) had 2-4, 140 (3.6%) 5-9, and 2 (0.1%) ≥10. Most women and heterosexual men (91.7%) had one past gonorrhoea diagnosis; none had more than four. Reduced ceftriaxone and cefixime susceptibility was more common among MSM with two to four gonorrhoea diagnoses (3.8% and 5.8%, respectively) compared with those with one (2.2% and 3.9%, respectively). After adjusting for potential confounding, this association remained (adjusted OR: 1.59, 95% CI 1.07 to 2.37, p=0.02; adjusted OR: 1.54, 95% CI 1.11 to 2.14, p=0.01). No evidence was found for any other associations. CONCLUSIONS: Among MSM, repeat diagnosis of gonorrhoea may be associated with reduced ceftriaxone and cefixime susceptibility. As these are last-line therapies for gonorrhoea, further research is needed to assess the impact of intensive STI screening on AMR.

Three-site screening for STIs in men who have sex with men using online self-testing in an English sexual health service.

OBJECTIVES: Among men who have sex with men (MSM) in the UK,Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) infections commonly occur asymptomatically at extragenital sites. Therefore, MSM seeking sexual health services are offered three-site (oropharyngeal, rectal and urogenital) STI screening. To increase access to screening, some UK sexual health services enable asymptomatic service users to order free STI screening kits online for self-sampling at home. We sought to assess prevalence of overall and extragenital CT/NG infection among asymptomatic MSM who used online self-testing in Hampshire, UK. METHODS: We assessed prevalence of CT/NG infections from non-pooled samples among asymptomatic cisgender MSM using an administrative database with results from 5601 STI screening kits returned between 20 December 2016 and 31 January 2020. We compared number of diagnoses of extragenital infection with urogenital results of the same individuals to determine prevalence of infection that would have been missed with urine testing alone. RESULTS: Among 5051 valid CT and 5040 valid NG asymptomatic test results, overall prevalence was 5.9% (298/5051) and 4.5% (228/5040), respectively. Among MSM with asymptomatic CT, 71.8% (214/298) had extragenital infection only, χ2 (1, n=298)=56.71, p<0.001. Among those with asymptomatic NG, 89.9% (205/228) had extragenital infection only, χ2 (1, n=228)=145.281, p<0.001. CONCLUSIONS: Overall, most CT/NG infections among asymptomatic MSM who used online self-testing were extragenital. Given this and the likelihood of onward transmission from asymptomatic infection, it is recommended that three-site testing remain standard for MSM and free screening services be expanded in easily accessible ways.

The effectiveness of an extra-curricular lecture for STI prevention and sexual education.

While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs.

Improvement in Neisseria gonorrhoeae culture rates by bedside inoculation and incubation at a clinic for sexually transmitted infections.

BACKGROUND: Culture of Neisseria gonorrhoeae is essential for surveillance of complete antimicrobial susceptibility profiles. In 2014, the culture success rate of N. gonorrhoeae from samples taken at the clinic for sexually transmitted infections (STI clinic), Oslo University Hospital, Norway, was only 20%. The present study aimed to improve gonococcal culture rates using bedside inoculation of patient samples on gonococcal agar plates and incubation at the STI clinic. METHODS: This prospective quality improvement study was conducted by the STI clinic and the Department of Microbiology at Oslo University Hospital from May 2016 - October 2017. When culture of N. gonorrhoeae was clinically indicated, we introduced a parallel 'bedside culture' at the STI clinic and compared results with the standard culture at the microbiology department. Samples were taken from urethra, anorectum, pharynx and cervix. Culture rates were compared across symptomatic and asymptomatic anatomical sites. RESULTS: From 596 gonococcal-positive PCR samples, bedside culture had a significantly higher success rate of 57% compared to 41% with standard culture (p < 0.05). Overall, culture rate from symptomatic sites was 91% v. 45% from asymptomatic sites. The culture rates from different anatomical sites were as follows: urethra 93%, anorectum 64%, pharynx 28% and cervix 70%. Bedside culture significantly (p < 0.05) improved the culture rates for symptomatic urethral and asymptomatic pharyngeal samples. CONCLUSIONS: Where feasible, bedside inoculation on gonococcal agar plates and incubation of samples from patients with gonorrhoea is recommended. This will improve the culture diagnostics and provide additional gonococcal isolates for antimicrobial resistance surveillance.

Serine acetyltransferase from Neisseria gonorrhoeae; structural and biochemical basis of inhibition.

Serine acetyltransferase (SAT) catalyzes the first step in the two-step pathway to synthesize l-cysteine in bacteria and plants. SAT synthesizes O-acetylserine from substrates l-serine and acetyl coenzyme A and is a key enzyme for regulating cellular cysteine levels by feedback inhibition of l-cysteine, and its involvement in the cysteine synthase complex. We have performed extensive structural and kinetic characterization of the SAT enzyme from the antibiotic-resistant pathogen Neisseria gonorrhoeae. Using X-ray crystallography, we have solved the structures of NgSAT with the non-natural ligand, l-malate (present in the crystallization screen) to 2.01 Šand with the natural substrate l-serine (2.80 Å) bound. Both structures are hexamers, with each monomer displaying the characteristic left-handed parallel ß-helix domain of the acyltransferase superfamily of enzymes. Each structure displays both extended and closed conformations of the C-terminal tail. l-malate bound in the active site results in an interesting mix of open and closed active site conformations, exhibiting a structural change mimicking the conformation of cysteine (inhibitor) bound structures from other organisms. Kinetic characterization shows competitive inhibition of l-cysteine with substrates l-serine and acetyl coenzyme A. The SAT reaction represents a key point for the regulation of cysteine biosynthesis and controlling cellular sulfur due to feedback inhibition by l-cysteine and formation of the cysteine synthase complex. Data presented here provide the structural and mechanistic basis for inhibitor design and given this enzyme is not present in humans could be explored to combat the rise of extensively antimicrobial resistant N. gonorrhoeae.