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Background: The emergence of ceftriaxone-resistant Neisseria gonorrhoeae poses a significant threat to existing treatment regimens. Our study aimed to assess the efficacy of antimicrobials that could be combined with ceftriaxone to reduce the probability of ceftriaxone resistance emerging and spreading in N. gonorrhoeae ., Methods and Results: Broth microdilution was used to determine the minimal inhibitory concentrations (MICs) for a panel of ceftriaxone-resistant (WHO X, Y, Z) and ceftriaxone-susceptible (WHO L, N, P) N. gonorrhoeae WHO reference strains for the following antimicrobials: ceftriaxone, doxycycline, azithromycin, zoliflodacin, fosfomycin, pristinamycin, ramoplanin, gentamicin and NAI-107. The MICs for zoliflodacin and pristinamycin for all strains were lower than or equal to the available breakpoints. A checkerboard assay was used to determine the drug-drug combination effect, which showed either an indifferent or an additive effect for all the combinations tested with ceftriaxone., Conclusions: The low MICs of zoliflodacin and pristinamycin for the three ceftriaxone-resistant strains suggest that these antimicrobials could be used as partner drugs with ceftriaxone to reduce the probability of ceftriaxone resistance spreading in areas with a high prevalence of ceftriaxone resistance., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The 2022 mpox epidemic reached a peak in Belgium and the rest of Europe in July 2022, after which it unexpectedly subsided. This study investigates epidemiological, behavioral, and immunological factors behind the waning of the epidemic in Belgium., Methods: We investigated temporal evolutions in the characteristics and behavior of mpox patients using national surveillance data and data from a prospective registry of mpox patients in the Institute of Tropical Medicine (Antwerp). We studied behavioral changes in the population at risk using a survey among HIV-preexposure prophylaxis (PrEP) users. We determined the seroprevalence of anti-orthopoxvirus antibodies among HIV-PrEP users across four-time points in 2022., Results: Mpox patients diagnosed at the end of the epidemic had less sexual risk behavior compared to those diagnosed earlier: they engaged less in sex at mass events, had fewer sexual partners, and were less likely to belong to the sexual network's central group. Among HIV-PrEP users there were no notable changes in sexual behavior. Anti-orthopoxvirus seroprevalence did not notably increase before the start of national vaccination campaigns., Conclusion: The observed changes in group immunity and behavior in the population at greater risk of exposure to mpox seem unable to explain the waning of the mpox epidemic. A change in the profile of mpox patients might have contributed to the decline in cases., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: We aimed to assess the awareness, willingness to use and use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR)., Methods: Cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organisations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with χ 2 or Fisher's exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR., Results: 875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32-48), 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the previous 6 months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with reporting ≥1 sexually transmitted infection (STI) in the previous 12 months, engagement in chemsex, HIV status and pre-exposure prophylaxis use, and education level.About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use decreased to 60% and concerns of side effects/AMR increased to around 70%., Conclusions: Approximately 1 in 10 MSM in Belgium reported using doxyPEP. A recent history of STIs and STI risk factors were positively associated with doxyPEP use. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction. Commensal Neisseria spp. are highly prevalent in the oropharynx as part of the healthy microbiome. N. meningitidis can colonise the oropharynx too from where it can cause invasive meningococcal disease. To identify N. meningitidis , clinical microbiology laboratories often rely on Matrix Assisted Laser Desorption/Ionisation Time of Flight Mass Spectrometry (MALDI-TOF MS). Hypothesis/Gap statement. N. meningitidis may be misidentified by MALDI-TOF MS. Aim. spp. in order to: (i) verify MALDI-TOF MS species identification, and (ii) characterize commensal Neisseria spp. in order to: (i) verify MALDI-TOF MS species identification, and (ii) characterize commensal Neisseria spp. genomes. Methodology. We analysed whole genome sequence (WGS) data from 119 Neisseria spp. in Belgium. Different species identification methods were compared: (i) MALDI-TOF MS, (ii) Ribosomal Multilocus Sequence Typing (rMLST) and (iii) Neisseria spp. in Belgium. Different species identification methods were compared: (i) MALDI-TOF MS, (ii) Ribosomal Multilocus Sequence Typing (rMLST) and (iii) rplF gene species identification. WGS data were used to further characterize Neisseria species found with supplementary analyses of Neisseria cinerea genomes. Results. Based on genomic species identification, isolates from the oropharyngeal Neisseria surveilence study were composed of the following species: N. meningitidis ( n =23) , N. subflava ( n =61), N. mucosa ( n =15), N. oralis ( n =8), N. cinerea ( n =5), N. elongata ( n =3), N. lactamica ( n =2), N. bacilliformis ( n =1) and N. polysaccharea ( n =1). Of these 119 isolates, four isolates identified as N. meningitidis ( n =3) and N. subflava ( n =1) by MALDI-TOF MS , were determined to be N. polysaccharea ( n =1) , N. cinerea ( n =2) and N. mucosa ( n =1) by rMLST. Phylogenetic analyses revealed that N. cinerea isolates from the general population ( n =3, cluster one) were distinct from those obtained from men who have sex with men (MSM, n =2, cluster two). The latter contained genomes misidentified as N. meningitidis using MALDI-TOF MS. These two N. cinerea clusters persisted after the inclusion of published N. cinerea WGS ( n =42). Both N. cinerea clusters were further defined through pangenome and Average Nucleotide Identity (ANI) analyses. Conclusion. This study provides insights into the importance of genomic genus-wide Neisseria surveillance studies to improve the characterization and identification of the Neisseria genus.

Objectives: Antimicrobial resistance poses a considerable threat in high-antimicrobial-consumption populations, such as men who have sex with men (MSM) taking HIV pre-exposure prophylaxis. While the ResistAZM trial found no increase in macrolide resistance genes in MSM with gonorrhea after azithromycin treatment, the MORDOR trial observed an increase in these genes after mass azithromycin distribution. We hypothesized that this could be due to saturation of the resistome. To test this hypothesis, we compared the abundance of macrolide resistance determinants in anorectal samples between the baselines of the two trials., Methods: Shotgun metagenome reads from the anorectal baseline samples from the ResistAZM (n = 42) and MORDOR (n = 30) trials were analyzed using AMRPlusPlus. Nonhost reads were mapped to the MEGARes database to detect antibiotic resistance genes (ARG). Antimicrobial resistance (AMR) was normalized using cumulative sum scaling, and ARG abundance was estimated., Results: Macrolide, lincosamides, and streptogramins determinants were approximately 10-fold more abundant in the ResistAZM than the MORDOR samples (P ≤ 0.001)., Conclusion: The findings are compatible with our hypothesis. Thus, in populations with high-antimicrobial use, the relationship between antimicrobial consumption and AMR may be diminished due to saturation. These findings are vital for future studies investigating the resistogencity of novel interventions, such as doxycycline post-exposure prophylaxis, in populations with high preceding consumption of antimicrobials., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Tetracycline and macrolide resistance are frequently linked in streptococci and other species. We aimed to assess the association between doxycycline use and azithromycin MICs in oral streptococci., Methods: Linear regression was used to assess the association between doxycycline use in the prior year and the median MIC per participant of oral streptococcal colonies isolated at the baseline visit of the ResistAZM study. The analysis controlled for receipt of other antimicrobials as well as time since antimicrobial consumption., Results: Fifty-six individual colonies confirmed to be streptococci were isolated from 19 individuals at baseline. The azithromycin MICs of these isolates varied considerably between 0.25 mg/L and >256 mg/L (median 28 mg/L; IQR 1-192 mg/L). The consumption of doxycycline in the preceding 12 months was positively associated with median streptococcal azithromycin MIC (coef. 151.6 [95% CI 10.6-292.7]; p = .037)., Conclusion: This post-hoc analysis found that doxycycline use was associated with streptococcal azithromycin susceptibility. Numerous limitations of the study design mean that this study is best considered hypothesis generating. Prospective studies are required to assess if the use of doxycycline could select for macrolide resistance in oral streptococci., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tolerance enables bacteria to survive intermittent antibiotic exposure without an increase in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone, azithromycin and ciprofloxacin, in clinical isolates and the WHO (World Health Organization) reference panel of Neisseria gonorrhoeae ., Methods: We used the modified tolerance disk (TD test) to assess for tolerance to ceftriaxone, azithromycin and ciprofloxacin in 14 WHO reference strains and 62 N. gonorrhoeae clinical isolates-evenly divided between anorectal and urogenital infections. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disk for 20 h of incubation (Step I), followed by the replacement of the antibiotic disk with a nutrient disk for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III)., Results: A total of 4 of the 62 clinical anorectal isolates and none of the urogenital isolates exhibited tolerance to azithromycin ( p = 0.033). Tolerance to ceftriaxone and ciprofloxacin was observed in eight and four isolates, respectively, with no difference between infection sites. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO reference strains, with varying patterns of tolerance to ceftriaxone ( n = 8), ciprofloxacin ( n = 2) and azithromycin ( n = 1)., Conclusions: This study identified ceftriaxone, azithromycin and ciprofloxacin tolerance in clinical and WHO reference N. gonorrhoeae isolates. Azithromycin tolerance was more common in anorectal than urogenital infections.

Introduction and Objectives: The HepHIV 2023 Conference, held in Madrid in November 2023, highlighted how Europe is not on track to meet the United Nations (UN) sustainable development goals and Joint UN Programme on HIV/AIDS (UNAIDS) targets. This article presents the outcomes of the conference, which focus on ways to improve testing and linkage to care for HIV, viral hepatitis, and other sexually transmitted infections. HIV-related stigma and discrimination, a major barrier to progress, was a key concept of the conference and on the agenda of the Spanish Presidency of the European Union., Methods: The HepHIV 2023 organizing committee, alongside the Spanish Ministry of Health, oversaw the conference organization and prepared the scientific programme based on abstract rankings. Key outcomes are derived from conference presentations and discussions., Results: Conference presentations covered the obstacles that HIV-related stigma and discrimination continue to pose to access to services, models for data collection to better monitor progress in the future, and examples of legislative action that can be taken at national levels. Diversification of testing approaches was also highlighted, to reach key populations, (e.g. migrant populations), to increase testing offered in healthcare settings (e.g. emergency departments), and to account for different stages of epidemics across the region., Conclusion: With a strong call for intensified action to address the impact of HIV-related stigma and discrimination on testing uptake, the conference concluded that strengthened collaboration is required between governments and implementers around testing and linkage to care. There is also an ongoing need to ensure sustainable political commitment and appropriate resource allocation to address gaps and inequalities in access for key populations and to focus on the implementation of integrated responses to HIV, viral hepatitis, and sexually transmitted infections., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objectives: The burden of HIV and other sexually transmitted infections (STIs) remains high in sex workers globally, calling for strengthening targeted prevention strategies, including HIV pre-exposure prophylaxis (PrEP). The study's objective was to assess HIV and STI burden among female, male and transgender sex workers in Flanders, Belgium, to guide targeting of PrEP strategies for sex workers., Methods: We conducted a retrospective analysis of routine data collected between January 2016 and December 2019 by community-based organisations providing sexual healthcare services for sex workers in Flanders. HIV prevalence stratified by gender was assessed and associations with sociodemographic characteristics were explored using bivariable and multivariable logistic regression. Positivity rates of chlamydia, gonorrhoea and syphilis tests were used as proxy indicators for STI burden., Results: The study included a total of 6028 sex workers, comprising 5617 (93.2%) female, 218 (3.6%) male and 193 (3.2%) transgender sex workers. The HIV prevalence was 0.3% among female, 8.9% among male and 12.3% among transgender sex workers. Engaging in escort sex work and originating from South America or Sub-Saharan Africa were associated with a higher likelihood of having acquired HIV. The positivity rate for gonorrhoea was higher among male sex workers (5.2% vs 2.2%) and syphilis was more frequently detected among male and transgender sex workers (3.0% and 6.1% vs 0.5%), all compared with female sex workers., Conclusions: HIV combination prevention, including improved access to PrEP, should be strengthened among sex workers in Flanders, with particular attention to male and transgender sex workers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: CL has received a travel grant and fees for a meeting from Gilead Sciences. The other authors have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We aimed to assess whether a self-collected oral rinse was non-inferior to clinician-collected oropharyngeal swabs to detect Neisseria gonorrhoeae (Ng) using culture and nucleic acid amplification tests (NAAT) among men who have sex with men (MSM), and whether Ng may still be detected in oral rinses for a minimum of 5 days after collection., Methods: MSM with a positive Ng result in an oropharyngeal or pooled sample (oropharynx, urethra and anorectum) were approached. Clinician-collected oropharyngeal swabs and oral rinses (15 mL sterile water) were taken. Ng culture and NAAT (Abbott 2000m RealTime System CT/NG assay and in-house PCR) were performed. Diagnostic accuracy was assessed using sensitivity and specificity, and agreement between both techniques using Cohen's kappa statistic. Aliquots of positive oral rinses were left at room temperature for a minimum of 5 days and reanalysed using NAAT. Lastly, participants filled in a questionnaire to explore perceptions of both methods., Results: We included 100 participants between June 2022 and October 2023. 45 individuals (45 of 100) had a positive Ng result in either the oral rinses (42 of 45, 93%) or the swabs (36 of 45, 80%). Sensitivity was higher for oral rinses than swabs (sensitivity=0.93/0.80, specificity=1.0/1.0, respectively) and agreement between both techniques was good (kappa=0.75, p<0.001). Of the 42 positive oral rinses, 37 remained positive after a minimum of 5 days (88.1%). Using culture, 18 individuals had a positive Ng result in either the oral rinses (8 of 18, 44%) or the swabs (16 of 18, 88%). Most participants found the oral rinse easy or very easy to use and would be willing to use the oral rinse for home-based sampling., Conclusion: We detected more oropharyngeal Ng infections via NAAT using oral rinses than swab samples. However, swabs were better than oral rinses for culturing Ng. Oral rinses might allow for home-based self-sampling to detect oropharyngeal Ng., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The introduction of female-initiated drug-delivery methods, including vaginal rings, have proven to be a promising avenue to address sexually transmitted infections and unintended pregnancies, which disproportionally affects women and girls in sub-Saharan Africa. Efficient uptake of existing and new technologies such as vaginal rings requires in depth understanding of product adherence. This remains a major challenge as data on adherence to vaginal rings from African countries is limited. In this study, we explored adherence of contraceptive vaginal ring (NuvaRing®) use in Kigali, Rwanda using a mixed methods approach., Methods: We collected quantitative and qualitative data at multiple time points from women participating in a clinical trial exploring the safety and acceptability of either intermittent or continuous use of the NuvaRing®. Various adherence categories were used including monthly and cumulative adherence measurement. The quantitative data were analysed using R and the qualitative data were analysed using a deductive, content-analytical approach based on categories related to the quantitative adherence measures. All data were compared and triangulated., Results: Data from 120 enrolled participants showed that self-reported adherence was high at every study visit in both study groups. At first study visit 80% of the intermittent ring users and 79.7% of the continuous ring users reported perfect adherence (assessed as "the ring was never out"). Reporting of ring expulsions and removals were highest (28.3%) at the beginning of the trial. Self-reported perfect ring adherence increased during the study and reports of ring expulsions and removals declined as familiarity with this contraceptive method increased. The percentage of women with perfect cumulative adherence was non-significantly higher in the intermittent (61.7%) than in the continuous use group (54.3%). The low rate of discrepant adherence data after triangulation (6%) is in line with the perception of the participants as adherent throughout the study., Conclusions: Self-reported adherence in both study groups was high with removals and expulsions being within the expected product range. Comprehensive adherence data triangulation allowed for a deeper understanding of context-driven behaviour that shaped adherence patterns and challenges. Our data categorisation and triangulation approach has shown potential for implementation in future vaginal ring studies aiming to better understand and measure adherence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kestelyn, Van Nuil, Umulisa, Umutoni, Uwingabire, De Baetselier, Uwineza, Agaba, Crucitti, Delvaux and van de Wijgert.)

Background: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP., Methods: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed., Findings: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported., Interpretation: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population., Funding: Belgian Health Care Knowledge Centre., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

BackgroundAntimicrobial resistance (AMR) of Mycoplasma genitalium (MG) is a growing concern worldwide and surveillance is needed. In Belgium, samples are sent to the National Reference Centre of Sexually Transmitted Infections (NRC-STI) on a voluntary basis and representative or robust national AMR data are lacking.AimWe aimed to estimate the occurrence of resistant MG in Belgium.MethodsBetween July and November 2022, frozen remnants of MG-positive samples from 21 Belgian laboratories were analysed at the NRC-STI. Macrolide and fluoroquinolone resistance-associated mutations (RAMs) were assessed using Sanger sequencing of the 23SrRNA and parC gene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioural variables via Fisher's exact test and logistic regression analysis.ResultsOf the 244 MG-positive samples received, 232 could be sequenced for macrolide and fluoroquinolone RAMs. Over half of the sequenced samples (55.2%) were resistant to macrolides. All sequenced samples from men who have sex with men (MSM) (24/24) were macrolide-resistant. Fluoroquinolone RAMs were found in 25.9% of the samples and occurrence did not differ between socio-demographic and sexual behaviour characteristics.ConclusionAlthough limited in sample size, our data suggest no additional benefit of testing MG retrieved from MSM for macrolide resistance in Belgium, when making treatment decisions. The lower occurrence of macrolide resistance in other population groups, combined with emergence of fluoroquinolone RAMs support macrolide-resistance testing in these groups. Continued surveillance of resistance in MG in different population groups will be crucial to confirm our findings and to guide national testing and treatment strategies.

One of the most promising new treatments for gonorrhoea currently in phase 3 clinical trials is zoliflodacin. Studies have found very little resistance to zoliflodacin in currently circulating N. gonorrhoeae strains, and in-vitro experiments demonstrated that it is difficult to induce resistance. However, zoliflodacin resistance may emerge in commensal Neisseria spp., which could then be transferred to N. gonorrhoeae via transformation. In this study, we investigated this commensal-resistance-pathway hypothesis for zoliflodacin. To induce zoliflodacin resistance, ten wild-type susceptible isolates belonging to 5 Neisseria species were serially passaged for up to 48 h on gonococcal agar plates containing increasing zoliflodacin concentrations. Within 7 to 10 days, all strains except N. lactamica, exhibited MICs of ≥ 4 µg/mL, resulting in MIC increase ranging from 8- to 64-fold. The last passaged strains and their baseline were sequenced. We detected mutations previously reported to cause zoliflodacin resistance in GyrB (D429N and S467N), novel mutations in the quinolone resistance determining region (QRDR) (M464R and T472P) and mutations outside the QRDR at amino acid positions 28 and 29 associated with low level resistance (MIC 2 µg/mL). Genomic DNA from the laboratory evolved zoliflodacin-resistant strains was transformed into the respective baseline wild-type strain, resulting in MICs of ≥ 8 µg/mL in most cases. WGS of transformants with decreased zoliflodacin susceptibility revealed presence of the same zoliflodacin resistance determinants as observed in the donor strains. Two inter-species transformation experiments were conducted to investigate whether zoliflodacin resistance determinants of commensal Neisseria spp. could be acquired by N. gonorrhoeae. N. gonorrhoeae strain WHO P was exposed to (i) pooled genomic DNA from the two resistant N. mucosa strains and (ii) a gyrB amplicon of the resistant N. subflava strain 45/1&#95;8. Transformants of both experiments exhibited an MIC of 2 µg/mL and whole genome analysis revealed uptake of the mutations detected in the donor strains. This is the first in-vitro study to report that zoliflodacin resistance can be induced in commensal Neisseria spp. and subsequently transformed into N. gonorrhoeae., (© 2024. The Author(s).)

Background: commensal Neisseria species are part of the oropharyngeal microbiome and play an important role in nitrate reduction and protecting against colonization by pathogenic bacteria. They do, however, also serve as a reservoir of antimicrobial resistance. Little is known about the prevalence of these species in the general population, how this varies by age and how antimicrobial susceptibility varies between species., Methods: we assessed the prevalence and antimicrobial susceptibility of commensal Neisseria species in the parents (n = 38) and children (n = 50) of 35 families in Belgium., Results: various commensal Neisseria (n = 5) could be isolated from the participants. Most abundant were N. subflava and N. mucosa. Neisseria subflava was detected in 77 of 88 (87.5%) individuals and N. mucosa in 64 of 88 (72.7%). Neisseria mucosa was more prevalent in children [41/50 (82%)] than parents [23/38 (60.5%); P < .05], while N. bacilliformis was more prevalent in parents [7/36 (19.4%)] than children [2/50 (4%); P < .05]. Neisseria bacilliformis had high ceftriaxone minimum inhibitory concentrations (MICs; median MIC 0.5 mg/l; IQR 0.38-0.75). The ceftriaxone MICs of all Neisseria isolates were higher in the parents than in the children. This could be explained by a higher prevalence of N. bacilliformis in the parents., Interpretation: the N. bacilliformis isolates had uniformly high ceftriaxone MICs which warrant further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Neisseria gonorrhoeae is a bacterial pathogen that causes gonorrhoea, a sexually transmitted infection. Increasing antimicrobial resistance in N. gonorrhoeae is providing motivation to develop new treatment options. In this study, we investigated the effectiveness of the antibiotic ramoplanin as a treatment for N. gonorrhoeae infection. We tested the effectiveness of ramoplanin in vitro against 14 World Health Organization (WHO) reference strains of N. gonorrhoeae and found that it was active against all 14 strains tested. Furthermore, in a Galleria mellonella infection model of N. gonorrhoeae WHO P, we demonstrated that ramoplanin was active in vivo without any evidence of toxicity. This suggests that ramoplanin might be a new promising antibiotic treatment for gonorrhoea.

Importance: We screened 66 bacteriocins to see if they exhibited anti-gonococcal activity. We found 12 bacteriocins with anti-gonococcal effects, and 4 bacteriocins showed higher anti-gonococcal activity. Three bacteriocins, lacticin Z, lacticin Q, and Garvicin KS (ABC), showed in vitro anti-gonococcal activity but no in vivo inhibitory effects against the Neisseria gonorrhoeae (WHO-P) isolate. On the other hand, NAI-107 showed in vivo anti-gonococcal activity. The findings suggest that NAI-107 is a promising alternative to treat gonorrhea infections., Competing Interests: The authors declare no conflict of interest.

Background: Four randomized controlled trials have now established that doxycycline post exposure (sex) prophylaxis (PEP) can reduce the incidence of chlamydia and syphilis in men who have sex with men. These studies have concluded that the risk of selecting for antimicrobial resistance is low. We evaluated this risk in vitro and in vivo using a Galleria mellonella infection model., Methods: We evaluated how long it took for doxycycline resistance to emerge during passage on doxycycline containing agar plates in 4 species - Escherichia coli , Klebsiella pneumoniae , Neisseria gonorrhoeae and Neisseria subflava . We then assessed if K. pneumoniae could acquire resistance to doxycycline (and cross resistance to other antimicrobials) during intermittent exposure to doxycycline in a Galleria mellonella model of doxycycline PEP., Results: In our passage experiments, we found that resistance first emerged in K. pneumoniae . By day 7 the K. pneumoniae MIC had increased from 2 mg/L to a median of 96 mg/L (IQR 64-96). Under various simulations of doxycycline PEP in the G. mellonella model, the doxycycline MIC of K. pneumoniae increased from 2 mg/L to 48 mg/L (IQR 48-84). Ceftriaxone and ciprofloxacin MICs increased over ten-fold. Whole genome sequencing revealed acquired mutations in ramR which regulates the expression of the AcrAB-TolC efflux pump., Conclusion: Doxycycline PEP can select for doxycycline, ceftriaxone and ciprofloxacin resistance in K. pneumoniae in a G. mellonella model. The emergent ramR mutations were similar to those seen in circulating strains of K. pneumoniae . These findings suggest that we need to assess the effect of doxycycline PEP on resistance induction on a broader range of bacterial species than has hitherto been the case., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kenyon, Gestels, Vanbaelen, Abdellati, Van Den Bossche, De Baetselier, Xavier and Manoharan-Basil.)

Introduction: Daily and event-driven oral pre-exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use irrespective of the chosen PrEP regimens among men who have sex with men (MSM)., Methods: Using data from a mobile, web-based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be-PrEP-ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event-driven oral PrEP every 3 months. We used group-based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories., Results: We included 516 MSM (n = 322 AMPrEP; n = 194 Be-PrEP-ared), of whom 24% chose event-driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow-up (median = 508 days [IQR = 429-511]). Four distinct PrEP use trajectories were identified: ≤2 tablets per week ("low frequency," 12% of the total population), 4 tablets per week ("variable," 17%), "almost daily" (31%) and "always daily" (41%). Compared to participants with "low frequency" PrEP use, participants with "variable" (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.04-4.60) and "almost daily" PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27-5.49). "Almost daily" PrEP users were more often employed (OR = 6.76, 95% CI = 2.10-21.75) and were younger compared to participants with "low frequency" PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with "low frequency" PrEP use compared to the other groups (all p<0.001). Compared to "low frequency" PrEP users, the incidence rates of chlamydia and gonorrhoea were higher for participants with "almost daily" and "always daily" PrEP use., Conclusions: We uncovered four distinct PrEP use trajectories, pointing to different patterns of PrEP use in practice beyond the two-regimen dichotomy. These trajectories were related to sexual behaviour and rates of sexually transmitted infection. Tailoring PrEP care according to different PrEP use patterns could be an important strategy to improve efficient PrEP delivery., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Abstract: The Treponema pallidum strain distribution among men who have sex with women were similar to the strain distribution men who have sex with men. The most prevalent strains and percentage of strains belonging to the Nichols lineage are similar to previous studies in Amsterdam focusing on men who have sex with men., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: Phenotypic studies have found high levels of antimicrobial resistance to cephalosporins, macrolides and fluoroquinolones in commensal Neisseria species in the oropharynx of men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP). These species include Neisseria subflava and Neisseria mucosa. This may represent a risk to pathogens like Neisseria gonorrhoeae which tend to take up antibiotic resistance genes (ARGs) from other bacteria. We aimed to explore to what extent the oropharyngeal resistome of MSM using PrEP differed from the general population., Methods: We collected oropharyngeal swabs from 32 individuals of the general population and from 64 MSM using PrEP. Thirty-two MSM had consumed antibiotics in the previous six months, whereas none of the other participants had. Samples underwent shotgun metagenomic sequencing. Sequencing reads were mapped against MEGARes 2.0 to estimate ARG abundance. ARG abundance was compared between groups by zero-inflated negative binomial regression., Findings: ARG abundance was significantly lower in the general population than in MSM (ratio 0.41, 95% CI 0.26-0.65). More specifically, this was the case for fluoroquinolones (0.33, 95% CI 0.15-0.69), macrolides (0.37, 95% CI 0.25-0.56), tetracyclines (0.41, 95% CI 0.25-0.69), and multidrug efflux pumps (0.11, 95% CI 0.03-0.33), but not for beta-lactams (1.38, 95% CI 0.73-2.61). There were no significant differences in ARG abundance between MSM who had used antibiotics and those that had not., Interpretation: The resistome of MSM using PrEP is enriched with ARGs, independent of recent antibiotic use. Stewardship campaigns should aim to reduce antibiotic consumption in populations at high risk for STIs., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2023 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Mpox (formerly monkeypox) is a viral disease caused by the mpox virus (MPXV), endemic in Central and West Africa and currently causing a global outbreak of international concern. Much remains unknown about sample types most suited for mpox laboratory diagnosis. While it is established that high viral loads can be found in active skin lesions (currently the recommended mpox laboratory confirmation specimen type), WHO mpox testing guidelines encourage the use of oropharyngeal swabs as an additional sample type for mpox diagnosis and suggest investigating the value of other specimens like blood samples., Objective: In this study, we verified the value of select alternative specimen types for mpox laboratory confirmation., Methods: We included 25 patients with MPXV-confirmed skin lesions to compare diagnostic sensitivity of MPXV PCR testing on EDTA plasma and two upper respiratory specimens: oropharyngeal swabs and saliva., Results: In our patient cohort with MPXV-confirmed skin lesions, diagnostic sensitivity of MPXV PCR was 80% in EDTA plasma, 64% in oropharyngeal swabs, and 88% in saliva. MPXV viral loads were significantly higher in saliva compared to oropharyngeal swabs and EDTA plasma., Discussion: The WHO recommendation to collect oropharyngeal swabs as an additional specimen for mpox diagnosis might need to be revised to include saliva wherever feasible. We suggest investigating saliva as a diagnostic specimen in the absence of active skin lesions or during the phase preceding skin manifestations. Moreover, the relatively high MPXV DNA content of saliva warrants elucidating its potential role in disease transmission., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO-F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO-F WT and WHO-F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence. Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance. Conclusions:   We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 González N et al.)

Background: Antimicrobial resistance to macrolides and fluoroquinolones in Mycoplasma genitalium (MG) among men who have sex with men (MSM) is worryingly high in high-resource countries. Data in Africa are lacking. We aimed to assess the burden of MG including the presence of resistance-associated mutations (RAMs) in MG among MSM using human immunodeficiency virus preexposure prophylaxis in Burkina Faso, Côte d'Ivoire, Mali, and Togo., Methods: MSM were included in a prospective cohort study (2017-2021). Molecular detection of MG in urine, anorectal, and pharyngeal samples was performed at baseline and after 6 and 12 months. Detection of RAMs to macrolides and fluoroquinolones was performed by sequencing the 23S ribosomal RNA, parC , and gyrA genes. A sample was found to be possibly resistant to fluoroquinolones if alterations were found in ParC position 83/87., Results: Of 598 participants, 173 (28.9%) were positive at least once for MG and global point-prevalence was 19.4%. Interestingly, 238 of 250 (95.2%) infections were asymptomatic and 72 of 138 MG infections with follow-up data (52.2%) cleared during the study. Only 1 macrolide RAM was found (0.6%). Prevalence of fluoroquinolones RAMs was 11.3% overall, ranging from 2.4% in Burkina Faso to 17.5% in Mali., Conclusions: Although MG was highly prevalent in these MSM, macrolide resistance was almost nonexistent. Nevertheless, >10% of the samples were possibly resistant to fluoroquinolones. Heterogeneity in the prevalence of fluoroquinolone RAMs between countries may be explained by different antimicrobial consumption in humans and animals., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)