Rebound in sexually transmitted infections after the COVID-19 pandemic.

Sexually transmitted infections (STIs) have become the second in the global rating of infectious diseases after respiratory infections. Globally, over 1 million, new STI is diagnosed every day. Although four conditions are the most representative and of obligatory declaration (gonorrhea, syphilis, chlamydia, and human immunodeficiency virus [HIV]), there are many other prevalent STI, including trichomona, herpes simplex, papillomavirus, and viral hepatitis. Herein, we perform a narrative and retrospective review, analyzing information from public databases from distinct Spanish government institutions. STI significantly declined in Spain during 2020 as a result of lockdown and social isolation measures dictated in response to the COVID-19 pandemic. After releasing restrictions, a major STI rebound occurred in 2021. Increases were 49% for gonorrhea, 45% for HIV, 39% for chlamydia, and 32% for syphilis. Based on nationwide statistics, we build a narrative review of the recent STI surge after COVID-19. In summary, we propose a holistic approach to confront the current re-emergence of STI. On one hand, new innovative medical advances must be implemented, including new rapid tests, novel vaccines, pre-exposure prophylaxis beyond HIV, and long-acting antivirals. On the other hand, information to citizens needs to be reformulated with interventions aimed to build a healthier society, alike it has been undertaken with tobacco, alcohol, diet, and lifestyle. STI determines important sexual, reproductive, and maternal-child health consequences. To promote human well-being or flourishing, the education of adolescents and young adults should be aligned with human ecology. Therefore, it is urgent to address new approaches in sexual health that represent a clear benefit for individual persons and society. In this way, favoring a cultural evolution aimed to delay the age of first sexual intercourse and the avoidance of multiple sex partners should be prioritized.

Spatiotemporal Epidemiology of the Gonorrhea Epidemic in Relation to Neighborhood-level Structural Factors in an Eastern Province of China, 2016-2020.

Context: Gonorrhea, a highly communicable, sexually transmitted infection, remains a major public-health concern globally. In recent years, Zhejiang province, an eastern province, has had the highest incidence of gonorrhea in China. Objective: The study intended to identify the geographic distribution patterns and spaciotemporal clustering characteristics of the disease's incidence in Zhejiang between 2016 and 2020, to understand the spatial epidemiology of gonorrhea and to pinpoint the locations with relatively high risks of gonorrhea, the hotspots, which could be the key areas for disease prevention and control. Design: The research team performed a retrospective, spaciotemporal-clustering analysis of data about newly reported gonorrhea cases from January 2016 to December 2020 in Zhejiang province, using the China Information System for Disease Control and Prevention. Setting: The study took place at the Zhejiang Provincial Institute of Dermatology in Huzhou, China. Outcome Measures: The research team: (1) used the Geographic Information System software-ArcGIS 10.8 software to draw statistical maps; (2) conducted a spatial-pattern clustering analysis at the district or county level; (3) performed an autocorrelation analysis using Getis-Ord (Gi*) statistics to detect spatial patterns and the hotspots of gonorrhea incidence; and (4) used SaTScan9.7 to analyze the space-time clusters. Results: Zhejiang province reported 85 904 gonorrhea cases from 2016 to 2020, with a male to female ratio of 3.81:1. The average annual incidence rate of gonorrhea was 30.50 per 100 000 individuals in the population, ranging from 22.73 cases to 39.65 cases, and the annual incidence showed a significant downward trend over the five years (χ2 = 16.142, P < .001). The northern and central areas had a higher incidence than the southern area did. Autocorrelation analysis showed that the gonorrhea incidence had a significantly clustered distribution (Moran's I from 0.197 to 0.295, Z score from 4.749 to 6.909, P < .001). The high-high cluster areas were mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing. The Gi* statistics further indicated that the hotspots of gonorrhea were mainly in Hangzhou, Jiaxing, and Huzhou. The Kuldorff's scan identified two clusters, mainly composed of 36 counties or districts in northern Zhejiang, such as Hangzhou and Jiaxing, and central Zhejiang, such as Jinhua and Shaoxing. Conclusions: The gonorrhea incidence rates in northern and central Zhejiang from 2016 to 2020 were higher than those in southern Zhejiang. An area of relatively higher risk for gonorrhea existed mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing, Jinhua, and Shaoxing. In the future, the research team plans to focus on strengthening the prevention and control measures against gonorrhea in those areas.

Randomized controlled trial of the relative efficacy of high-dose intravenous ceftriaxone and oral cefixime combined with doxycycline for the treatment of Chlamydia trachomatis and Neisseria gonorrhoeae co-infection.

OBJECTIVES: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the commonest bacterial causes of sexually transmitted infections in humans with high incidence of co-infection. Treatment with high doses of ceftriaxone (CRO) and cefixime (CFM) is strongly recommended due to the reduced drug susceptibility of NG. However, their safety and efficacy have not been confirmed. We compared the safety and efficacy of a single 1 g intravenous (IV) dose of ceftriaxone (CRO) plus doxycycline (DOX) versus a single 800 mg oral dose of cefixime (CFM) plus DOX for the treatment of NG-CT co-infection. METHODS: An open-label randomized controlled trial was conducted on 125 individuals aged > 18 years with untreated gonorrhea and chlamydia to compare a single 1 g intravenous dose of CRO + DOX and a single 800 mg oral dose of CFM + DOX. The primary outcome was the clearance of NG from all the initially infected sites. Secondary outcomes included symptom resolution, changes in the serum clearance levels, glomerular filtration rate, and antibiotic minimum inhibitory concentrations. RESULTS: Both regimens were highly effective in treating gonorrhea with success rates of 96.7% (95% confidence interval [CI] 88.8-99.1%) for CRO and 95.3% (95% CI 87.1-98.4%) for CFM. However, CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection (odds ratio 4.41, 95% CI 1.11-25.7). The safety profiles of the two regimens were similar. CONCLUSIONS: CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection. CFM + DOX may be indicated in patients with CRO allergy and in settings where CRO is unavailable. Trial registration ClinicalTrials.gov (NCT05216744) on 31/01/22.

Sexually Transmitted Infection Testing, Prevalence, and Treatment Among Individuals Receiving HIV Preexposure Prophylaxis Within an Integrated Healthcare Delivery System.

BACKGROUND: Initial and follow-up sexually transmitted infection (STI) and human immunodeficiency virus (HIV) testing are recommended when taking HIV preexposure prophylaxis (PrEP). We assessed STI services before and after PrEP initiation among persons 18 years or older. METHODS: We conducted this retrospective cohort study at a US integrated healthcare delivery system. We measured HIV/STI testing rates, STI prevalence and treatment at 3 time points: (1) at PrEP initiation, (2) at 120 days, and (3) at 210 days. RESULTS: Of 685 PrEP initiators, 67.2% continued PrEP use at 120 days and 49.5% at 210 days. Of PrEP users, HIV and STI testing were greater than 85% and greater than 80%, respectively, at all 3 time points. Prevalence for any chlamydia, rectal chlamydia, and any gonorrhea, rectal gonorrhea, or pharyngeal gonorrhea was always high at the 120 days and 210 days (eg, 6.9%, 10.5%, 6.7%, 5.0%, and 5.2%, respectively, at the 120 days for continuous PrEP users). Over 90% of all individuals who tested positive for chlamydia and gonorrhea received antibiotic pharmacy fills within 7 days at 120 and 210 days. Monthly PrEP-related pharmacy cost was about $2259 to $2659. The proportion of the total medical cost that was PrEP-related pharmacy was about 82% for PrEP continuous users. CONCLUSIONS: Although HIV/STI testing rates were high, they can still be improved during HIV PrEP management. High STI prevalence after PrEP initiation in this study suggests that patients taking PrEP are at risk of acquiring an STI. Interventions to improve STI services during PrEP management are continuously needed.

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.

We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.

Management of Neisseria gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines.

INTRODUCTION: Neisseria gonorrhoeae has developed resistance to all first-line recommended therapies, making gonococcal antimicrobial resistance a major public health concern given limited antibiotic options currently and an even smaller antimicrobial development pipeline. Since the release of the Centers for Disease Control and Prevention (CDC) 2015 STD Treatment Guidelines, azithromycin, part of the 2015 dual-drug treatment regimen, has had a rapid rise in resistance. The 2020 CDC Gonorrhea Treatment Recommendations and the 2021 Sexually Transmitted Infections (STI) Treatment Guidelines were developed weighing the priorities of treating the individual, protecting the population, and preventing antimicrobial resistance. METHODS: Gonorrhea subject matter experts (SME) generated 8 key questions and conducted a literature review of updated data from 2013 to 2019 on gonorrhea antimicrobial resistance, treatment failures, clinical trials, and other key topics. More than 2200 abstracts were assessed, and 248 clinically relevant articles were thoroughly reviewed. SMEs also evaluated N gonorrhoeae antimicrobial resistance data from the Gonococcal Isolate Surveillance Project (GISP). EVIDENCE: Although there have been reports of ceftriaxone treatment failures internationally, GISP data suggest that ceftriaxone minimal inhibitory concentrations (MICs) have remained stable in the United States, with < 0.1% exhibiting an "alert value" MIC (> 0.25 mcg/mL). However, GISP documented a rapid rise in the proportion of isolates with an elevated MIC (≥ 2.0 mcg/mL) to azithromycin-nearly 5% in 2018. At the same time, new pharmacokinetic/pharmacodynamic data are available, and there is greater recognition of the need for antimicrobial stewardship. SUMMARY: The 2021 CDC STI Treatment Guidelines now recommend 500mg ceftriaxone intramuscularly once for the treatment of uncomplicated gonorrhea at all anatomic sites. If coinfection with chlamydia has not been excluded, cotreatment with doxycycline 100mg twice daily for 7 days should be added. Few alternative therapies exist for persons with cephalosporin allergies; there are no recommended alternative therapies for N gonorrhoeae infection of the throat.

Markedly Increasing Antibiotic Resistance and Dual Treatment of Neisseria gonorrhoeae Isolates in Guangdong, China, from 2013 to 2020.

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

Antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium isolates from the private healthcare sector in South Africa: A pilot study.

BACKGROUND: Reports have emerged globally of antimicrobial resistance (AMR) in Neisseria gonorrhoeae and Mycoplasma genitalium infections. In South Africa (SA), there are substantial differences between private and public healthcare with regard to antimicrobial drug prescribing practice, which could affect AMR patterns of private and public healthcare patients. OBJECTIVES: To perform a pilot study to determine the frequency of AMR of N. gonorrhoeae and M. genitalium in patients accessing SA's private healthcare sector. METHODS: In this cross-sectional study, N. gonorrhoeae-positive cultures and M. genitalium DNA samples were collected from a private healthcare reference laboratory from August 2018 to August 2019. In N. gonorrhoeae-positive cultures, antimicrobial susceptibility testing was performed, followed by N. gonorrhoeae multiantigen sequence typing (NG-MAST) to determine genetic relatedness of the isolates. To determine macrolide and fluoroquinolone resistance rates, M. genitalium-positive samples were analysed by sequencing the 23S rRNA, gyrA and parC genes. RESULTS: Twenty-one N. gonorrhoeae- and 27 M. genitalium-positive specimens were included in this analysis. High rates of resistance were detected among gonococcal isolates, with 90% resistance to tetracycline, 86% to penicillin and 62% to ciprofloxacin, but no resistance to azithromycin, cefixime and ceftriaxone. NG-MAST revealed genetically diverse isolates with 83% novel NG-MAST sequence types. Macrolide and fluoroquinolone resistance-associated mutations were detected in 18.5% (n=5/27) and 7.4% (n=2/27) of M. genitalium strains, respectively. CONCLUSIONS: We observed high frequencies of ciprofloxacin, penicillin and tetracycline resistance in N. gonorrhoeae and macrolide resistance-associated mutations in M. genitalium in private healthcare sector patients in SA. This finding highlights the need to use diagnostics for sexually transmitted infections and to include the private healthcare sector in antimicrobial surveillance and stewardship programmes.

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and syndromic treatment of men with urethral discharge in Kingston, Jamaica, 2018-19.

OBJECTIVES: To quantitatively determine the antimicrobial susceptibility of clinical Neisseria gonorrhoeae isolates from men with urethral discharge in Jamaica and to describe the syndromic treatment therapies administered. METHODS: Urethral eSwabs (Copan) were collected from 175 men presenting with urethral discharge to the Comprehensive Health Centre STI Clinic, Kingston, Jamaica. Clinical information was collected and MICs of eight antimicrobials were determined for N. gonorrhoeae isolates (n = 96) using Etest and interpreted using CLSI criteria. RESULTS: The median age of the subjects was 28 years (range: 18-73 years) with a median of 2 sexual partners (range: 1-25) per male in the previous 3 months. All examined N. gonorrhoeae isolates were susceptible to ceftriaxone (96/96), azithromycin (91/91), cefixime (91/91) and spectinomycin (91/91). For ciprofloxacin and gentamicin, respectively, 98.9% (91/92) and 91.3% (84/92) of the isolates were susceptible and 1.1% (1/92) and 8.7% (8/92) showed intermediate susceptibility/resistance. For tetracycline and benzylpenicillin, respectively, 38.0% (35/92) and 22.0% (20/91) of the isolates were susceptible, 52.2% (48/92) and 74.7% (68/91) showed intermediate susceptibility/resistance and 9.8% (9/92) and 3.3% (3/91) were resistant. Syndromic treatment was administered as follows: 93.1% received 250 mg of ceftriaxone intramuscularly plus 100 mg of doxycycline orally q12h for 1-2 weeks and 6.9% received 500 mg of ciprofloxacin orally plus 100 mg of doxycycline orally q12h for 1 week. CONCLUSIONS: Ceftriaxone (250 mg) remains appropriate for gonorrhoea treatment in the examined population of men in Kingston, Jamaica. Surveillance of N. gonorrhoeae AMR should be expanded in Jamaica and other Caribbean countries to guide evidence-based treatment guidelines.

Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009-2019.

BACKGROUND: Limited antimicrobial resistance (AMR) data for Neisseria gonorrhoeae are available in Eastern Europe. We investigated AMR in N. gonorrhoeae isolates in the Republic of Belarus from 2009 to 2019, antimicrobial treatment recommended nationally, and treatment given to patients with gonorrhoea. METHODS: N. gonorrhoeae isolates (n = 522) cultured in three regions of Belarus in 2009-2019 were examined. Determination of minimum inhibitory concentrations (MICs) of eight antimicrobials was performed using Etest. Resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing were applied where available. A Nitrocefin test identified ß-lactamase production. Gonorrhoea treatment for 1652 patients was also analysed. Statistical significance was determined by the Z-test, Fisher's exact test, or Mann-Whitney U test with p-values of < 0.05 indicating significance. RESULTS: In total, 27.8% of the N. gonorrhoeae isolates were resistant to tetracycline, 24.7% to ciprofloxacin, 7.0% to benzylpenicillin, 2.7% to cefixime, and 0.8% to azithromycin. No isolates were resistant to ceftriaxone, spectinomycin, or gentamicin. However, 14 (2.7%) isolates had a ceftriaxone MIC of 0.125 mg/L, exactly at the resistance breakpoint (MIC > 0.125 mg/L). Only one (0.2%) isolate, from 2013, produced ß-lactamase. From 2009 to 2019, the levels of resistance to ciprofloxacin and tetracycline were relatively high and stable. Resistance to cefixime was not identified before 2013 but peaked at 22.2% in 2017. Only sporadic isolates with resistance to azithromycin were found in 2009 (n = 1), 2012 (n = 1), and 2018-2019 (n = 2). Overall, 862 (52.2%) patients received first-line treatment according to national guidelines (ceftriaxone 1 g). However, 154 (9.3%) patients received a nationally recommended alternative treatment (cefixime 400 mg or ofloxacin 400 mg), and 636 (38.5%) were given non-recommended treatment. CONCLUSIONS: The gonococcal resistance to ciprofloxacin and tetracycline was high, however, the resistance to azithromycin was low and no resistance to ceftriaxone was identified. Ceftriaxone 1 g can continuously be recommended as empiric first-line gonorrhoea therapy in Belarus. Fluoroquinolones should not be prescribed for treatment if susceptibility has not been confirmed by testing. Timely updating and high compliance with national evidence-based gonorrhoea treatment guidelines based on quality-assured AMR data are imperative. The need for continued, improved and enhanced surveillance of gonococcal AMR in Belarus is evident.

Chlamydia trachomatis, Neisseria gonorrhoea, and Trichomonas vaginalis infections among pregnant women and male partners in Dutch midwifery practices: prevalence, risk factors, and perinatal outcomes.

BACKGROUND: Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI. METHODS: Cross-sectional study. Pregnant women aged ≤ 30 years (n = 548) and male partners (n = 425) were included at 30 midwifery practices during 2012-2016. Participants provided a self-collected vaginal swab (women) or urine sample (men) and completed a questionnaire. Perinatal data were derived from pregnancy cards. APO was defined as premature rupture of membranes, preterm delivery, low birthweight, stillbirth, neonatal conjunctival and respiratory infections. Data were analysed by logistic regression. RESULTS: STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of young women (≤ 20 years), 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age (≤ 20 years vs ≥ 21 years) (adjusted OR 6.52, CI 95%: 1.11-38.33), male non-Western vs Western background (aOR 9.34, CI 2.34-37.21), and female with ≥ 2 sex partners < 12 months vs 0-1 (aOR 9.88, CI 2.08-46.91). APO was not associated with STI, but was associated with female low education (aOR 3.36, CI 1.12-10.09), complications with previous newborn (aOR 10.49, CI 3.21-34.25 vs no complications) and short duration (0-4 years) of relationship (aOR 2.75, CI 1.41-5.39 vs ≥ 5 years). Small-for-gestational-age was not associated with STI, but was associated with female low education (aOR 7.81, 2.01-30.27), female non-Western background (aOR 4.41, 1.74-11.17), and both parents smoking during pregnancy (aOR 2.94, 1.01-8.84 vs both non-smoking). CONCLUSIONS: Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO, which is probably due to low prevalence of STI, small study sample, and presumed treatment for STI.

Antenatal screening for HIV, syphilis and HBV has been successfully implemented in The Netherlands, but data on other STI among pregnant women or male partners are limited. Our objectives were: (i) to assess the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among pregnant women and male partners, (ii) to identify risk factors for these STI during pregnancy, and (iii) to identify adverse perinatal outcomes (APO) associated with STI.Pregnant women aged ≤ 30 years and male partners were included at 30 midwifery practices. Women provided a vaginal swab, partners a urine sample; both completed a questionnaire. Perinatal data were derived from midwives.STI were present in 2.4% of pregnant women (CT 1.8%, NG 0.4%, TV 0.4%), and in 2.2% of male partners (CT 2.2%, NG 0.2%, TV 0%). Of women ≤ 20 years, 12.5% had a CT infection. Prevalent STI during pregnancy was associated with female young age, male non-Western background, and female with ≥ 2 sex partners < 12 months. APO was not associated with STI, but was associated with female low education, complications with previous newborn, and short duration of the relationship. Small-for-gestational-age was not associated with STI, but was associated with female low education, female non-Western background, and both parents smoking during pregnancy.Prevalence of STI was low among pregnant women and male partners in midwifery practices, except for CT among young women. The study could not confirm previously observed associations between STI and APO. Probably due to low prevalence of STI, small study sample, and presumed treatment for STI.

Developing a model to predict individualised treatment for gonorrhoea: a modelling study.

OBJECTIVE: To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone. DESIGN: A modelling study. SETTING: England and Wales. PARTICIPANTS: Individuals accessing sentinel health services. INTERVENTION: Developing an Excel model which uses participants' demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015-2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme. MAIN OUTCOME MEASURES: Estimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation. RESULTS: Between 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%-51%) and penicillin (range: 6%-33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment. CONCLUSIONS: Using demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.

Epidemiology, Treatments, and Vaccine Development for Antimicrobial-Resistant Neisseria gonorrhoeae: Current Strategies and Future Directions.

Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection in the world after Chlamydia trachomatis. The pathogen has developed resistance to every antibiotic currently approved for treatment, and multidrug-resistant strains have been identified globally. The current treatment recommended by the World Health Organization is ceftriaxone and azithromycin dual therapy. However, resistance to azithromycin and ceftriaxone are increasing and treatment failures have been reported. As a result, there is a critical need to develop novel strategies for mitigating the spread of antimicrobial-resistant N. gonorrhoeae through improved diagnosis and treatment of resistant infections. Strategies that are currently being pursued include developing molecular assays to predict resistance, utilizing higher doses of ceftriaxone, repurposing older antibiotics, and developing newer agents. In addition, efforts to discover a vaccine for N. gonorrhoeae have been reignited in recent years with the cross-protectivity provided by the N. meningitidis vaccine, with several new strategies and targets. Despite the significant progress that has been made, there is still much work ahead to combat antimicrobial-resistant N. gonorrhoeae globally.

Efficacy of 1 g Ceftriaxone Monotherapy Compared to Dual Therapy With Azithromycin or Doxycycline for Treating Extragenital Gonorrhea Among Men Who Have Sex With Men.

BACKGROUND: Evidence on efficacy of high-dose ceftriaxone monotherapy for extragenital Neisseria gonorrhoeae (NG) infection is lacking. METHODS: A cohort of men who have sex with men (MSM) were tested for NG/Chlamydia trachomatis (CT) every 3 months, in a single-center observational study in Tokyo, Japan. MSM aged > 19 years diagnosed with extragenital NG infection between 2017 and 2020 were included. A single dose of 1 g ceftriaxone monotherapy was provided, while dual therapy with a single oral dose of 1 g azithromycin or 100 mg doxycycline administered orally twice daily for 7 days were given, for those coinfected with CT, according to infected sites. Efficacy of these treatments was calculated by the number of NG-negative subjects at test-of-cure divided by the number of subjects treated. Fisher exact tests were used to compare the efficacy between the 2 groups. RESULTS: Of 320 cases diagnosed with extragenital NG, 208 were treated with monotherapy and 112 were treated with dual therapy. The efficacy against total, pharyngeal, and rectal infections was 98.1% (204/208, 95% confidence interval [CI]: 95.2-99.3%), 97.8% (135/138, 95% CI: 93.8-99.4%), and 98.6% (69/70, 95% CI: 92.3-99.9%), respectively, in the monotherapy group, whereas the corresponding efficacy in the dual therapy was 95.5% (107/112, 95% CI: 90.0-98.1%), 96.1% (49/51, 95% CI: 86.8-99.3%), and 95.1% (58/61, 95% CI: 86.5-98.7%), respectively. No significant difference in the corresponding efficacy was observed between the two groups (P = .29, P = .61, P = .34, respectively). CONCLUSIONS: High-dose ceftriaxone monotherapy is as effective as dual therapy for extragenital NG among MSM.

Associations between antimicrobial susceptibility/resistance of Neisseria gonorrhoeae isolates in European Union/European Economic Area and patients' gender, sexual orientation and anatomical site of infection, 2009-2016.

BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae, nationally and internationally, is a serious threat to the management and control of gonorrhoea. Limited and conflicting data regarding the epidemiological drivers of gonococcal AMR internationally have been published. We examined the antimicrobial susceptibility/resistance of gonococcal isolates (n = 15,803) collected across 27 European Union/European Economic Area (EU/EEA) countries in 2009-2016, in conjunction to epidemiological and clinical data of the corresponding patients, to elucidate associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection. METHODS: In total, 15,803 N. gonorrhoeae isolates from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 2009-2016, were examined. Associations between gonococcal susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection were investigated using univariate and multivariate logistic regression analysis. Statistical significance was determined by Pearson χ2-test or Fisher's exact test with two-tailed p-values of < 0.05 indicating significance. RESULTS: The overall gonococcal resistance from 2009 to 2016 was 51.7% (range during the years: 46.5-63.5%), 7.1% (4.5-13.2%), 4.3% (1.8-8.7%), and 0.2% (0.0-0.5%) to ciprofloxacin, azithromycin, cefixime, and ceftriaxone, respectively. The level of resistance combined with decreased susceptibility to ceftriaxone was 10.2% (5.7-15.5%). Resistance to cefixime and ciprofloxacin, and resistance combined with decreased susceptibility to ceftriaxone were positively associated with urogenital infections and heterosexual males, males with sexual orientation not reported and females (except for ciprofloxacin), i.e. when compared to men-who-have-sex-with-men (MSM). Azithromycin resistance was positively associated with heterosexual males, but no association was significant regarding anatomical site of infection. CONCLUSIONS: Overall, sexual orientation was the main variable associated with gonococcal AMR. Strongest positive associations were identified with heterosexual patients, particularly males, and not MSM. To provide evidence-based understanding and mitigate gonococcal AMR emergence and spread, associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection need to be further investigated in different geographic settings. In general, these insights will support identification of groups at increased risk and targeted public health actions such as intensified screening, 3-site testing using molecular diagnostics, sexual contact tracing, and surveillance of treatment failures.

Gonorrhoea treatment combined with population-level general cephalosporin and quinolone consumption may select for Neisseria gonorrhoeae antimicrobial resistance at the levels of NG-MAST genogroup: An ecological study in Europe.

OBJECTIVES: The prevalence of Neisseria gonorrhoeae NG-MAST genogroup G1407, associated with decreased susceptibility to extended-spectrum cephalosporins and fluoroquinolone resistance, has declined in Europe and it switched from circulating predominantly in men who have sex with men (MSM) in 2009-2010 to heterosexuals in 2013. We hypothesise that changes to gonorrhoea treatment guidelines combined with differences in country-level consumption of cephalosporins and quinolones contributed to this shift. METHODS: Linear regression was used to evaluate the association between changes in prevalence of G1407 between 2009-2010 and 2013 and country-level consumption of quinolones and cephalosporins in 2011/12 in 20 European countries. RESULTS: Whilst the prevalence of G1407 declined between 2009-2010 and 2013 in the EU/EEA, its absolute prevalence increased by 10% or more in three countries. The national prevalence of G1407 in 2013 was positively associated with population-level general cephalosporin and quinolone consumption in the preceding 2 years. The association between the prevalence of G1407 and proportion of the national sample derived from MSM was non-significant in 2009-2010 and was negative in 2013. CONCLUSIONS: Our results are broadly compatible with the hypothesis that changes in gonorrhoea therapy to the more efficacious ceftriaxone (plus azithromycin) from 2010 to 2011 onwards resulted in a reduced prevalence of the resistance-associated G1407 overall but in MSM in particular. High population-level consumption of quinolones and cephalosporins in certain countries then contributed to the selection of G1407 predominantly in heterosexuals in these countries.

Trends in antimicrobial resistance in Neisseria gonorrhoeae in Hanoi, Vietnam, 2017-2019.

BACKGROUND: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an emerging global health threat. Surveillance of AMR in N. gonorrhoeae in the Western Pacific Region is important, as resistant strains have typically emerged from this region. There are sparse data regarding antibiotic susceptibility of N. gonorrhoeae from Vietnam. This study aimed to provide updated data on antibiotic susceptibilities in N. gonorrhoeae isolates from Hanoi, Vietnam. METHODS: From 2017 to 2019, 409 N. gonorrhoeae clinical isolates were collected at the National Hospital for Venereology and Dermatology in Hanoi, Vietnam. Antibiotic susceptibility testing was performed by disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) protocol. The zone diameters of inhibition were recorded and interpreted according to standard CLSI criteria, except for azithromycin, due to the absence of CLSI interpretation. Categorical variables were analyzed by Chi-square and Fisher's exact tests. Linear regression was used to evaluate zones of inhibition by year. RESULTS: Among the 409 isolates, no isolates were susceptible to penicillin, 98.3% were resistant to ciprofloxacin, and all isolates were susceptible to spectinomycin. There were 122/407 (30.0%) isolates resistant to azithromycin and there was an association between resistance and year (p <  0.01), ranging from 15.3% of isolates in 2017 to 46.7% of the isolates in 2018. Resistance to cefixime was found in 13/406 (3.2%) of isolates and there was no association by year (p = 0.30). Resistance to ceftriaxone occurred in 3/408 (0.7%) of isolates. Linear regression indicated the zone of inhibition diameters decreased by 0.83 mm each year for ceftriaxone (95% CI: - 1.3, - 0.4; p <  0.01) and decreased by 0.83 mm each year (95% CI: - 1.33, - 0.33; p <  0.01) for azithromycin; the association was not significant for cefixime (p = 0.07). CONCLUSIONS: We found decreasing susceptibility of N. gonorrhoeae to ceftriaxone and azithromycin, as well as a high prevalence of resistance to azithromycin, among isolates in Hanoi, Vietnam from 2017 to 2019. The trends of decreasing susceptibility to first-line treatments are concerning and highlight the urgency of addressing antimicrobial resistance in N. gonorrhoeae. Expanded surveillance efforts within the Western Pacific Region are critical to monitoring trends and informing treatment guidelines.

Assuring Adequate Treatment for Persons Diagnosed With Gonorrhea in New York State.

BACKGROUND: From November 2014 to May 2016, 57 local health departments in New York State (NYS) excluding New York City were offered a performance incentive (PI) to promote adherence to federally recommended treatment guidelines for gonorrhea. The rationale of the PI was to delay antibiotic resistance and disrupt transmission through attaining a high percentage of treatment adherence. METHODS: Surveillance data from the NYS Communicable Disease Electronic Surveillance System were used for analysis. We evaluated adherence per Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines for persons 12 years and older reported with uncomplicated gonorrhea during 4 time frames: Pre-PI, PI One, PI Two, and Post-PI. We measured adherence per the Centers for Disease Control and Prevention sexually transmitted disease treatment guidelines during each respective time frame and conducted χ tests to test for the association between treatment adequacy and time frame. RESULTS: During the Pre-PI, treatment was adequate in 82.0% of persons diagnosed with gonorrhea. After program implementation, treatment adequacy increased significantly (92.1% of diagnosed persons during PI One, 90.4% during PI Two, and 90.5% during the Post-PI; P ≤ 0.0001). The most common reason for inadequate or missing treatment was patient lost to follow-up. CONCLUSIONS: Public health intervention by the NYS Department of Health improved local health department adherence to federally recommended gonorrhea treatment guidelines, and improvements were maintained after the completion of the PI.

Plasmid mediated penicillin and tetracycline resistance among Neisseria gonorrhoeae isolates from Kenya.

BACKGROUND: Treatment of gonorrhea is complicated by the development of antimicrobial resistance in Neisseria gonorrhoeae (GC) to the antibiotics recommended for treatment. Knowledge on types of plasmids and the antibiotic resistance genes they harbor is useful in monitoring the emergence and spread of bacterial antibiotic resistance. In Kenya, studies on gonococcal antimicrobial resistance are few and data on plasmid mediated drug resistance is limited. The present study characterizes plasmid mediated resistance in N. gonorrhoeae isolates recovered from Kenya between 2013 and 2018. METHODS: DNA was extracted from 36 sub-cultured GC isolates exhibiting varying drug resistance profiles. Whole genome sequencing was done on Illumina MiSeq platform and reads assembled de-novo using CLC Genomics Workbench. Genome annotation was performed using Rapid Annotation Subsystem Technology. Comparisons in identified antimicrobial resistance determinants were done using Bioedit sequence alignment editor. RESULTS: Twenty-four (66.7%) isolates had both ß-lactamase (TEM) and TetM encoding plasmids. 8.3% of the isolates lacked both TEM and TetM plasmids and had intermediate to susceptible penicillin and tetracycline MICs. Twenty-six (72%) isolates harbored TEM encoding plasmids. 25 of the TEM plasmids were of African type while one was an Asian type. Of the 36 isolates, 31 (86.1%) had TetM encoding plasmids, 30 of which harbored American TetM, whereas 1 carried a Dutch TetM. All analyzed isolates had non-mosaic penA alleles. All the isolates expressing TetM were tetracycline resistant (MIC> 1 mg/L) and had increased doxycycline MICs (up to 96 mg/L). All the isolates had S10 ribosomal protein V57M amino acid substitution associated with tetracycline resistance. No relation was observed between PenB and MtrR alterations and penicillin and tetracycline MICs. CONCLUSION: High-level gonococcal penicillin and tetracycline resistance in the sampled Kenyan regions was found to be mediated by plasmid borne blaTEM and tetM genes. While the African TEM plasmid, TEM1 and American TetM are the dominant genotypes, Asian TEM plasmid, a new TEM239 and Dutch TetM have emerged in the regions.