Urogenital Gonorrhea Research Articles

Gonorrhea and Chlamydia Opt-Out Screening of Justice-Involved Females During Intake at the Los Angeles County Jail: The Pivotal Role of Correctional Health Systems.

Chlamydia and gonorrhea are two of the most common sexually transmitted infections (STIs) worldwide, presenting major public health challenges and resulting in billions of dollars in direct medical costs in the U.S. Incarcerated females have a particularly elevated risk of these infections, which can result in serious sequelae if left untreated. On December 13, 2021, the Los Angeles County Jail system began offering opt-out urogenital chlamydia and gonorrhea screening to all newly incarcerated females. We retrospectively analyzed electronic health record data for completed urogenital chlamydia/gonorrhea screening among newly incarcerated females between December 13, 2021, and May 31, 2023. We used multivariable logistic regression to examine the association of STIs and treatment non-initiation outcomes with various demographic and self-reported variables. Of the 13,739 female entrants offered STI testing, 10,717 (78%) completed screening, with 1151 (11%) having a chlamydial infection, 788 (7%) having a gonococcal infection, and 1626 (15%) having >1 infection. STI positivity was associated with age 18-34, reported houselessness, amphetamine use, and history of a positive prior treponemal antibody test. STI treatment non-initiation was associated with shorter jail stay for both chlamydial ([aOR] = 87.4, 95% CI (34.2, 223.2)) and gonococcal ([aOR] = 9.0, 95% CI (5.2, 15.7)) infections. The STI prevalence among female detainees tested was manyfold higher than that of the general population. The implementation of routine opt-out STI screening in carceral settings provides a unique opportunity to benefit the health of both the correctional population and potentially that of the surrounding community.

Interactions between Zoliflodacin and Neisseria gonorrhoeae Gyrase and Topoisomerase IV: Enzymological Basis for Cellular Targeting.

Gyrase and topoisomerase IV are the cellular targets for fluoroquinolones, a critically important class of antibacterial agents used to treat a broad spectrum of human infections. Unfortunately, the clinical efficacy of the fluoroquinolones has been curtailed by the emergence of target-mediated resistance. This is especially true for Neisseria gonorrhoeae, the causative pathogen of the sexually transmitted infection gonorrhea. Spiropyrimidinetriones (SPTs), a new class of antibacterials, were developed to combat the growing antibacterial resistance crisis. Zoliflodacin is the most clinically advanced SPT and displays efficacy against uncomplicated urogenital gonorrhea in human trials. Like fluoroquinolones, the primary target of zoliflodacin in N. gonorrhoeae is gyrase, and topoisomerase IV is a secondary target. Because unbalanced gyrase/topoisomerase IV targeting has facilitated the evolution of fluoroquinolone-resistant bacteria, it is important to understand the underlying basis for the differential targeting of zoliflodacin in N. gonorrhoeae. Therefore, we assessed the effects of this SPT on the catalytic and DNA cleavage activities of N. gonorrhoeae gyrase and topoisomerase IV. In all reactions examined, zoliflodacin displayed higher potency against gyrase than topoisomerase IV. Moreover, zoliflodacin generated more DNA cleavage and formed more stable enzyme-cleaved DNA-SPT complexes with gyrase. The SPT also maintained higher activity against fluoroquinolone-resistant gyrase than topoisomerase IV. Finally, when compared to zoliflodacin, the novel SPT H3D-005722 induced more balanced double-stranded DNA cleavage with gyrase and topoisomerase IV from N. gonorrhoeae, Escherichia coli, and Bacillus anthracis. This finding suggests that further development of the SPT class could yield compounds with a more balanced targeting against clinically important bacterial infections.

The Territorial Distribution of Incidence with Urogenital Chlamydia, Gonorrhea, and their Associated Complications in the Russian Federation

Relevance. Urogenital chlamydia is one of the most common sexually transmitted infections. Chlamydia often presents with minimal or no symptoms. However, it can be a major cause of pelvic inflammatory disease (PID), infertility, and ectopic pregnancy in women, as well as epididymitis, orchitis, and infertility in men. Aim. To study the territorial patterns of incidence of urogenital chlamydia, gonorrhea, and their associated complications in the Russian Federation in 2011 to 2019. Materials and methods. Official statistics on the incidence of urogenital chlamydia, gonorrhea, PID, female and male infertility in the Russian Federation were analyzed. Statistical analysis, graphing, table creation, data visualization, and research results analysis were conducted using Microsoft Excel 2010 and IBM SPSS Statistics 22 software. GIS mapping was performed using the GIS «Axioma». Results and discussion. From 2011 to 2019, the Russian Federation observed a decrease in the incidence of urogenital chlamydia, gonorrhea, and PID, while there was an increase in the incidence of male and female infertility. The geographical distribution remained stable, with areas characterized by consistently low and high incidence rates. A correlation was found between the incidence of urogenital chlamydia, gonorrhea, and their complications. The association between gonorrhea and PID was found to be more significant than the association between chlamydia and PID, possibly due to the higher risk of complications associated with gonorrhea. However, no correlation was found between gonorrhea and infertility, possibly because this complication manifests with a time delay and has multifactorial causes. Conclusions. Based on the presented data, it can be concluded that the incidence of urogenital chlamydia and gonorrhea affects the frequency of male and female infertility. Therefore, the implementation of screening examinations for sexually active individuals of reproductive age using appropriate laboratory diagnostic methods, along with the development of preventive measures for sexually transmitted infections, including urogenital chlamydia, is justified and should be widely practiced.

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

PurposeSingle 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.MethodsAntimicrobial susceptibility of three N. gonorrhoeae reference strains and 152 clinical isolates was assessed using standard disk diffusion, agar dilution, and epsilometer tests.ResultsGentamicin 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.ConclusionSelectively 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.

Anorectal Neisseria gonorrhoeae infections in women with and without reported anal sex and sex workers in sexual health centres in the Netherlands: a retrospective cohort study

Control of Neisseria gonorrhoeae infection (gonorrhoea) depends on effective testing strategies. Anorectal testing in women is often done on indication of anal sex; however, anorectal infections are seen with and without anal exposure, possibly caused by autoinoculation. This study aims to enhance understanding of anorectal infections in women, by identifying risk factors for anorectal diagnosis. In this retrospective cohort study we used national surveillance data from Dutch sexual health centres from Jan 1, 2016, to Dec 31, 2021. We included cisgender women having sex with men who were tested urogenitally and anorectally for gonorrhoea. Due to different testing policies, we identified three groups: women who had not reported recent anal sex (in the past 6 months), women who had reported recent anal sex, and sex workers. Extracted data for analyses included demographics, sexual behaviour, and diagnosis of a sexually transmitted infection (STI). Per group, multivariable models using Firth's penalised maximum likelihood logistic regression were constructed, identifying determinants of anorectal gonorrhoea among all women and among gonorrhoea-positive women only. Variables included in model construction were age, education level, migration background, number of partners, condom use, partner notification, STI symptoms, having a partner who has sex with men (MSM) or a migrant partner, previous STI test, anal sex, and chlamydia and gonorrhoea diagnoses per anatomical location. In total, 117 693 women were included: 43 757 women without reported recent anal sex, 51 728 women with reported recent anal sex, and 22 208 sex workers. In all three groups, around 2% of women were gonorrhoea positive, and 70% or more of women had an anorectal infection. The strongest determinant of anorectal gonorrhoea was a concurrent urogenital gonorrhoea diagnosis (adjusted odds ratios [aOR] 782 [95% CI 605-1018]) among women without reported recent anal sex (612 [490-768] among women with reported recent anal sex, and 464 [335-652] among sex workers). Among gonorrhoea-positive women, determinants of anorectal gonorrhoea were urogenital and anorectal chlamydia co-infection (aOR 2·03 [95% CI 1·38-3·02], for women without reported anal sex) and migration background (1·44 [1·02-2·06], for women with reported anal sex). Determinants among sex workers were condomless sex (2·43 [1·55-3·82]), anal sex (1·71 [1·10-2·66]), MSM or migrant partner (1·78 [1·13-2·79]), and urogenital and anorectal chlamydia co-infection (2·28 [1·11-5·14]). These findings support the possibility of an autoinoculation process from the urogenital to the anorectal location due to the very strong correlation between urogenital and anorectal gonorrhoea, and due to the similarity of results across all three groups. Current testing strategies could miss anorectal infections, which should be considered when developing gonorrhoea prevention and control guidelines. None.

Single-dose cefixime 800 mg plus doxycycline 100 mg twice a day for 7 days compared with single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g for treatment of urogenital, rectal, and pharyngeal gonorrhoea: a randomised clinical trial

ObjectivesTo evaluate the efficacy and tolerability of a single dose of oral cefixime 800 mg plus oral doxycycline 100 mg twice a day for 7 days, compared with a recommended single dose of ceftriaxone plus single dose of oral azithromycin, for treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhoea. MethodsA noninferiority, open-label, multicentre randomized controlled trial was conducted in Prague, Czech Republic. Some 161 patients, 18–65 years of age diagnosed with uncomplicated urogenital, rectal, or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomized to treatment with single dose of cefixime 800 mg plus doxycycline 100 mg twice a day for 1 week or a single dose of ceftriaxone 1 g intramuscularly plus single dose of azithromycin 2 g. The primary outcome was the number of participants with negative culture and NAAT at 1 week and 3 weeks, respectively, after treatment initiation. ResultsIn all, 161 patients were randomized and 152 were included in per-protocol analyses. All 76 (100%; 95% CI, 0.95–1.00) patients treated with ceftriaxone plus azithromycin achieved negative cultures and NAAT after treatment. In the cefixime plus doxycycline arm at week 1, culture was negative in all 76 (100%) patients; at week 3, culture was negative in 70 of the 76 patients (92%; 95% CI, 0.84–0.97) and NAAT negative in 66 of the 76 patients (87%; 95% CI, 0.77–0.94). At week 3, culture and NAAT were negative in 65 of the 76 patients (86%; 95% CI, 0.76–0.93). Per-protocol risk difference was 14.5%; 95% CI, 6.56–22.38. All treatment failures observed in the cefixime arm were pharyngeal gonorrhoea cases. DiscussionThe combination of cefixime and doxycycline did not achieve noninferiority to ceftriaxone and azithromycin for treatment of gonorrhoea when including pharyngeal gonorrhoea. It did, however, show high efficacy for urogenital and rectal gonorrhoea.

Efficacy and Safety of Gepotidacin as Treatment of Uncomplicated Urogenital Gonorrhea (EAGLE-1): Design of a Randomized, Comparator-Controlled, Phase 3 Study.

Gonorrhea, caused by Neisseria gonorrhoeae (NG), is the second most common bacterial sexually transmitted infection (STI). Rates of antimicrobial resistance to standard care are increasing worldwide, with many antibiotic classes now ineffective against NG. Gepotidacin is a first-in-class,bactericidal, triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by inhibition of two enzymes, where a single target-specific mutation does not significantly impact susceptibility. Gepotidacin confers activity against NG, including most strains resistant to marketed antibiotics. Here, we describe the design of a phase 3 clinical trial (EAGLE-1; NCT04010539) evaluating gepotidacin for the treatment of uncomplicated urogenital gonorrhea. This phase 3, randomized, multicenter, sponsor-blinded, noninferiority study across six countries is comparing the efficacy of gepotidacin with ceftriaxone plus azithromycin in 400 patients with uncomplicated urogenital gonorrhea (microbiological intent-to-treat population) and assessing the safety of gepotidacin in approximately 600 patients (intent-to-treat population). Eligible participants 12years of age or older with clinical suspicion of urogenital gonococcal infection and a NG-positive urogenital sample and/or purulent discharge are randomized 1:1 to receive oral gepotidacin (2 × 3000mg 10-12h apart) or ceftriaxone (500mg, intramuscular) plus azithromycin (1g, oral). The primary endpoint is culture-confirmed bacterial eradication of NG from the urogenital site at the test-of-cure (days 4-8) visit. This trial was designed in accordance with US Food and Drug Administration (2015) and European Medicines Agency (2011) guidance, particularly the primary endpoint and microbiological evaluability requirements. This study will help characterize the risk-benefit profile of gepotidacin for treating uncomplicated urogenital gonorrhea. Gepotidacin is an important potential treatment for gonorrhea to help address the urgent unmet need of multidrug resistance and the increasingly limited number of oral treatment options. ClinicalTrials.gov identifier, NCT04010539.

Bacterial sexually transmitted infections are concentrated in subpopulations of men who have sex with men using HIV pre-exposure prophylaxis.

Studies have shown varying trends in incidence of sexually transmitted infections (STIs) among individuals using HIV pre-exposure prophylaxis (PrEP). Characterization of individuals at increased risk for STIs may offer an opportunity for targeted STI screening. Group-based trajectory modeling. We screened participants from the AMPrEP demonstration project (2015-2020) for urogenital, anal, and pharyngeal chlamydia and gonorrhea, and syphilis every 3 months and when needed. We identified trajectories of STI incidence within individuals over time and determinants of belonging to a trajectory group. We calculated cumulative proportions of STIs within STI trajectory groups. Three hundred and sixty-six participants with baseline and at least one screening visit during follow-up were included (median follow-up time = 3.7 years [interquartile range, IQR = 3.5-3.7]). We identified three trajectories of STI incidence: participants with a mean of approximately 0.1 STIs per 3 months ('low overall', 52% of the population), participants with a mean 0.4 STI per 3 months ('medium overall', 43%), and participants with high and fluctuating (between 0.3 and 1 STIs per 3 months) STI incidence ('high and fluctuating', 5%). Participants in the 'low overall' trajectory were significantly older, and reported less chemsex and condomless anal sex with casual partners than participants in the other trajectories. Participants in the 'high and fluctuating' and 'medium overall' groups accounted for respectively 23 and 64% of all STIs observed during follow-up. STI incidence was concentrated in subpopulations of PrEP users who were younger, had more chemsex and condomless anal sex. Screening frequency for STIs could be reduced for subpopulations with low risk for incident STIs.

Epidemiological Overview of Urogenital Gonorrhea in Mexico (2003-2020).

In Mexico, urogenital gonorrhea (UG) is one of the main sexually transmitted diseases notifiable by health systems around the world. Epidemiological data on sexually transmitted infections (STIs) in Mexico indicated that UG was "under control" until 2017. However, international epidemiological reports indicate the increase in incidence due to several factors, including an increase during the first year of the COVID-19 pandemic. These factors suggest that this phenomenon may occur in developing countries, including Mexico. Therefore, the aim of this study was to analyze national surveillance data on UG from 2003-2019 and the first year of the COVID-19 pandemic. An epidemiological study of cases and incidence of UG (2003-2020) was performed in the annual reports issued by the General Directorate Epidemiology in Mexico. Cases and incidence were classified and analyzed by year, sex, age group, and seasons (by temperature). Distribution of UG was carried out using heat maps for the whole country. Ultimately, a seasonal and correlation analysis was performed for UG cases versus temperature. The results showed that the distribution of cases and incidence by sex showed that there was no variation over 14 years. From 2016 onward, a significant increase in UG was observed before the pandemic. During the first year of the pandemic, a significant increase was observed in females aged 24-44 years. A heterogeneous distribution of UG was identified; however, border states were ranked among the top states with elevated incidences and cases. Lastly, the occurrence of UG was associated with temperature, related to summer. The information presented is intended to be useful to promote prevention and to contribute to visualize the distribution of UG over the last 18 years for decision making, and to show one of the consequences of the collapse of epidemiological surveillance of UG during the first year of the COVID-19 pandemic.

Gepotidacin: a novel, oral, 'first-in-class' triazaacenaphthylene antibiotic for the treatment of uncomplicated urinary tract infections and urogenital gonorrhoea.

The ongoing spread of antimicrobial resistance has made the treatment of uncomplicated urinary tract infections (UTIs) and urogenital gonorrhoea increasingly difficult. New oral treatment options are urgently needed. Gepotidacin (previously GSK2140944) is a novel, bactericidal, oral, 'first-in-class' triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by blocking two essential topoisomerase enzymes. Mutations in both enzymes would likely be necessary for resistance to occur, thus raising hopes that the drug will be able to maintain long-term effectiveness. Data from Phase II clinical trials of gepotidacin in UTIs and urogenital gonorrhoea appear promising, and Phase III trials are underway. In this review we summarize the development of gepotidacin and discuss its potential role in clinical practice. If approved, gepotidacin will be the first new oral antibiotic for UTIs in more than 20 years.

Evaluation of a Statewide Online, At-Home Sexually Transmitted Infection and Human Immunodeficiency Virus Screening Program.

Innovative approaches such as online, at-home programs may address important barriers to sexually transmitted infection (STI) and human immunodeficiency virus (HIV) screening in the United States. This study evaluated the first year of an online, at-home program offering HIV and triple-site (urogenital, rectal, and pharyngeal) gonorrhea (GC) and chlamydia (CT) testing in Colorado. Test Yourself Colorado (TYC) is an online, at-home program that provides free mailed HIV tests and/or GC/CT tests to Colorado adults. Program use and outcomes between 1 June 2021 and 31 May 2022 were analyzed. A total of 1790 unique clients utilized TYC. Of 1709 clients who ordered HIV tests, 508 (29.7%) were men who have sex with men (MSM), and 41.3% (210/508) of these clients reported having never been tested for HIV before or were not tested in the prior year. Hispanic clients had lower STI test return rates (37.1%; 134/361) compared with non-Hispanic clients (45.9%; 518/1128) (P = .003). Positive STI tests were identified in 9.6% (68/708) of clients. Positive STI tests were more common in MSM clients (15.7%; 34/216) compared with all other sexual orientations (6.9%; 34/492) (P < .001). STI treatment was confirmed in 80.9% (55/68) of clients. The TYC online, home testing portal is a scalable tool that reaches clients at risk of STIs and HIV and navigates those with positive STI tests to treatment. HIV/STI home testing programs need to further assess and address utilization and outcomes for disparities by race and ethnicity to assure programs equitably benefit all at-risk communities.

Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 2022.

We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC-199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.

Assessing the National Representativeness of Estimates of Antimicrobial-Resistant Urogenital Neisseria gonorrhoeae in US Men, Gonococcal Isolate Surveillance Project, 2008-2018.

The percentage of Neisseria gonorrhoeae (GC) isolates with resistance or elevated minimum inhibitory concentrations to antimicrobials has steadily increased. Current estimates are based on the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance study of male GC in the United States. This analysis seeks to assess for adjustment before treating aggregated GISP estimates as nationally representative of all reported male urogenital infections. We used multilevel regression with poststratification (MRP) to compute national estimates of the proportion of antimicrobial resistance (AMR) (defined as exceeding minimum inhibitory concentration thresholds) in male GC using data from 2008 to 2018 GISP and case reports. Sensitivity analyses investigated the impact of analysis assumptions and unmeasured variables. We additionally produced estimates of 2018 AMR GC cases among US men. National estimates were consistent with unweighted estimates. The estimated proportion of incident AMR GC infections in men with urogenital GC in 2018 was 51.5% (95% confidence interval [CI], 50.1%-52.9%), equating to an estimated 366,300 incident AMR GC infections in US men aged 15 to 39 years. Estimates of AMR for tested antimicrobials in male GC infections in 2018 ranged from 0.16% (95% CI, 0.08%-0.24%) for ceftriaxone to 29.9% (95% CI, 28.6%-31.1%) for ciprofloxacin. Sensitivity analyses revealed that unmeasured data on sex of sex partners could substantially impact weighted estimates. Antimicrobial resistance among reported incident male urogenital GC infections remains rare for ceftriaxone, the current standard of care. Aggregated GISP data are generally representative of men in the US who are reported with urogenital gonorrhea.

Pharmacokinetic, Safety, and Tolerability Evaluations of Gepotidacin (GSK2140944) in Healthy Japanese Participants.

Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic in late-phase development for uncomplicated urinary tract infection and uncomplicated urogenital gonorrhea. Two clinical studies were conducted to assess the pharmacokinetics (PK) and interethnic comparisons of oral gepotidacin (free-base and to-be-marketed mesylate formulations) administered as single doses ranging from 1500 to 3000mg in fed and fasted states, and as 2×3000-mg doses given 12hours apart under fed conditions in healthy participants of Japanese ancestry. Dose proportionality was observed in plasma exposures, and comparable area under the concentration-time curve (AUC) and maximum concentration were observed in fed and fasted states. Interethnic comparisons for Japanese versus non-Japanese participant data showed slightly higher plasma maximum concentration (7%-30%) yet similar plasma AUCs; slightly lower urine AUCs (11%-18%) were observed. The slightly higher plasma exposures in healthy Japanese versus White participants in the same study were attributed to lower mean body weights (64kg versus ≈80kg). Adverse events were primarily gastrointestinal, and when administered with food, gastrointestinal tolerability was improved. Overall, the gepotidacin PK and safety-risk profiles in healthy Japanese support potential evaluation of the global clinical doses in future studies.

Novel Bacterial Topoisomerase Inhibitor Gepotidacin Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats.

Fluoroquinolone use in children is limited due to its potential toxicity and negative effects on skeletal development, but the actual effects/risks of fluoroquinolones on bone growth and the mechanisms behind fluoroquinolone-driven arthropathy remain unknown. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic with a unique mechanism of action that is not anticipated to have the same risks to bone growth as those of fluoroquinolones. Gepotidacin is in phase III clinical development for uncomplicated urinary tract infections (ClinicalTrials.gov identifiers NCT04020341 and NCT04187144) and urogenital gonorrhea (ClinicalTrials.gov identifier NCT04010539) in adults and adolescents ≥12 years of age. To inform arthropathy and other potential toxicity risks of gepotidacin in pediatric studies, this nonclinical study assessed oral gepotidacin toxicity in juvenile rats from postnatal day (PND) 4 to PND 32/35 (approximately equivalent to human ages from newborn to 11 years), using both in-life assessments (tolerability, toxicity, and toxicokinetics) and terminal assessments (necropsy with macroscopic and microscopic skeletal femoral head and/or stifle joint examinations). Gepotidacin doses of ≤300 mg/kg of body weight/day were well tolerated from PND 4 to PND 21, and higher doses of ≤1,250 mg/kg/day were well tolerated from PND 22 when the dose levels were escalated to maintain systemic exposure levels up to PND 35, with no observed treatment-related clinical signs, effects on mean body weight gain, or macroscopic findings on articular surfaces. A dose of 1,000 mg/kg/day was not tolerated during the dosing period from PND 4 to 21, with effects on body weight gain, fecal consistency, and body condition. Microscopic effects on articular surfaces were evaluated after 32 days of gepotidacin treatment at the highest tolerated dose. After 32 days of treatment with the highest tolerated gepotidacin dose of 300/1,250 mg/kg/day (systemic concentrations [area under the curve {AUC} values] of 93.7 μg · h/mL [males] and 121 μg · h/mL [females]), no skeletal effects on articular surfaces of the femoral head or stifle joint were observed. The absence of treatment-related clinical signs and arthropathy in juvenile rats provides evidence to support the potential future use of gepotidacin in children.

Systematic Review and Meta-Analysis to Estimate the Treatment Effect and Inform a Noninferiority Margin for a Phase 3 Noninferiority Trial in Uncomplicated Urogenital Gonorrhea.

Active-controlled noninferiority studies are used to investigate novel agents for uncomplicated urogenital gonorrhea (uUGC) as placebo-controlled trials are unethical. A systematic literature review and meta-analysis were conducted to estimate the ceftriaxone and proxy-for-placebo microbiological treatment effect and determine an appropriate noninferiority margin for phase 3 trials. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. To account for interstudy variability, a weighted, noniterative random-effects model was fitted using "R" software to estimate the microbiological response rate and 95% confidence intervals (CIs) for ceftriaxone and proxy-for-placebo (treatment with an antibiotic the isolate was subsequently confirmed resistant to, or spontaneous resolution without treatment). I2 , τ2 , and P values were computed and included in the meta-analysis forest plot. Seventeen studies were included in the meta-analysis; 14 reported ceftriaxone response in micro-intent-to-treat and microbiologically evaluable populations, and 3 reported proxy-for-placebo treatment response in uUGC (microbiologically evaluable population only). Microbiological treatment effect was estimated by subtracting the upper end of the CI for placebo from the lower end of the CI for ceftriaxone. Overall microbiological response was 98% (95% CI, 97-99) for ceftriaxone and 44% (95% CI, 34-54) for proxy-for-placebo, resulting in a microbiological treatment effect of 43%. A noninferiority margin of 15% preserved 65% of the ceftriaxone treatment effect, exceeding the 50% recommended per US Food and Drug Administration guidance for noninferiority studies. Results of this systematic literature review and meta-analysis could help inform the design, conduct, and analysis of future clinical studies in uUGC.

Trans-inclusive Sexual Health Questionnaire to Improve Human Immunodeficiency Virus/Sexually Transmitted Infection (STI) Care for Transgender Patients: Anatomic Site-Specific STI Prevalence and Screening.

In 2018, the municipal Sexual Health Clinic in Seattle, implemented trans-inclusive questions about sexual behavior, anatomy, gender-affirming surgeries, and sexually transmitted infection (STI) symptoms in the clinic's computer-assisted self-interview (CASI) to improve care for transgender and nonbinary (TNB) patients. We calculated test positivity, the proportion of TNB patient visits that received testing for human immunodeficiency virus (HIV); syphilis; pharyngeal, rectal, and urogenital gonorrhea (GC); and chlamydia (CT) before (5/2016-12/2018) and after (12/2018-2/2020) implementation of new CASI questions, and the proportion of asymptomatic patients who received anatomic site-specific screening based on reported exposures. There were 434 TNB patients with 489 and 337 clinic visits during each period, respectively. Nonbinary patients assigned male at birth (AMAB) had the highest prevalence of GC (10% pharyngeal, 14% rectal, 12% urogenital). Transgender women, transgender men, and nonbinary people AMAB had a high prevalence of rectal CT (10%, 9%, and 13%, respectively) and syphilis (9%, 5%, and 8%). Asymptomatic transgender women, transgender men, and nonbinary patients AMAB were more likely to receive extragenital GC/CT screening compared with nonbinary patients assigned female at birth. After implementation of trans-inclusive questions, there was a 33% increase in the number of annual TNB patient visits but no statistically significant increase in HIV/STI testing among TNB patients. TNB people had a high prevalence of extragenital STIs and syphilis. Implementation of trans-inclusive medical history questions at a clinic that serves cisgender and transgender patients was feasible and important for improving the quality of affirming and inclusive sexual healthcare.

Common treatment diagnoses in dermatological emergency services

Patients with avariety of dermatologic conditions, ranging from mild to life-threatening course of disease, present to the dermatological emergency service. The article provides an overview of prevalent conditions and recommendations for diagnosis and treatment according to guidelines. Major acute allergic diseases such as anaphylaxis, urticaria, angioedema and cutaneous drug reactions are discussed. In the field of infectious skin diseases, herpes zoster and erysipelas are common reasons for dermatological consultation. In recent years, scabies has reemerged. Educating patients properly about scabies management can prevent further treatment failures. Finally, the article focuses on sexually transmitted infections including urogenital gonorrhea and chlamydia.

Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial

Neisseria gonorrhoeae causes gonorrhoea, a common sexually transmitted infection. Emerging strains resistant to first-line ceftriaxone threaten N gonorrhoeae management. Hence, alternative treatments are needed. We aimed to evaluate the efficacy of ertapenem, gentamicin, and fosfomycin as alternative treatments for anogenital N gonorrhoeae. In a randomised, controlled, double-blind, non-inferiority trial (three experimental groups and one control group) at the Centre for Sexual Health in Amsterdam, Netherlands, we included adults aged 18 years or older, with anorectal or urogenital gonorrhoea. With random permuted blocks, participants were randomly assigned (1:1:1:1) to receive intramuscular 500 mg ceftriaxone (control group), intramuscular 1000 mg ertapenem, intramuscular 5 mg/kg gentamicin (maximum 400 mg), or oral 6 g fosfomycin. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the predefined primary infected site, 7-14 days after treatment. The primary analysis was per protocol (ie, excluding those lost to follow-up). The modified intention-to-treat analysis included all randomly assigned patients with anogenital gonorrhoea considering those lost-to-follow-up as treatment failure. Non-inferiority was established if the lower Hochberg-corrected 95% CI for difference between the experimental and control groups was greater than -10%. For the analysis of adverse events, we included all participants who received medication. The trial was registered at ClinicalTrials.gov (NCT03294395) and is complete. Between Sept 18, 2017, and June 5, 2020, from 2160 patients invited to participate, we assigned 346 (16%) participants to receive either ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), or fosfomycin (n=38). The fosfomycin group was terminated early after interim analysis revealed less than 60% efficacy. In the primary per-protocol analysis, 93 (100%) of 93 patients in the ceftriaxone group, 86 (99%) of 87 patients in the ertapenem group, 79 (93%) of 85 patients in the gentamicin group, and four (12%) of 33 patients in the fosfomycin group cleared N gonorrhoeae (risk difference vs ceftriaxone -0·01 [95% CI -0·08 to 0·05] for ertapenem and -0·07 [-0·16 to -0·01] for gentamicin). Thus, ertapenem proved non-inferior to ceftriaxone. In mITT analysis, risk differences versus ceftriaxone were -0·08 (-0·17 to 0·003) for ertapenem and -0·11 (-0·21 to -0·04) for gentamicin. We observed a higher proportion of patients with at least one adverse event in the ertapenem group (58 [56%] of 103) and fosfomycin group (36 [95%] of 38) versus the ceftriaxone group (24 [23%] of 103). Single-dose 1000 mg ertapenem is non-inferior to single-dose 500 mg ceftriaxone in gonorrhoea treatment. Yet, 5 mg/kg gentamicin (maximum 400 mg) is not non-inferior to ceftriaxone. Ertapenem is a potential effective alternative for anogenital N gonorrhoeae infections and merits evaluation for ceftriaxone-resistant infections. ZonMw and GGD-Amsterdam. For the Dutch translation of the abstract see Supplementary Materials section.

1358. A Real-World Study of the Burden of Illness and Treatment Patterns Among Patients with Uncomplicated Urogenital Gonorrhea in the United States

BackgroundGonorrhea (GC) is a major public health threat in the US. The Centers for Disease Control and Prevention (CDC) estimated direct healthcare costs of &271 million in 2018. CDC 2015 guidelines (applicable up to December 18, 2020) recommended cephalosporin plus azithromycin for GC. We used real-world data to assess patterns of inappropriate or suboptimal (IA/SO) or appropriate and optimal (AP&OP) antibiotic (AB) prescription (by CDC 2015 guidelines), and related healthcare costs, in US patients with uncomplicated urogenital GC (uUGG) diagnosed from July 1, 2013–June 30, 2018.MethodsA retrospective cohort study of IBM MarketScan data (commercial/Medicare claims) in patients ≥ 12 years old with uUGG. Eligible patients had an AB prescription ±5 days of uUGG diagnosis (index date) and continuous health-plan enrollment with ≥ 6 months’ baseline/≥ 12 months’ follow-up data. Patients with complicated urogenital GC were excluded. Patients were stratified by AB prescription (IA/SO or AP&OP; defined in Table 1) during the first uUGG episode (ie, within 30 days of index). Generalized linear models were used for multivariate analysis.Table 1. Definitions of appropriateness of AB prescriptions ResultsOf 2847 patients with uUGG (58.5% male), 77.1% had an IA/SO prescription (mostly due to IA AB class [~82.0%] and duration [24.0%]), while only 22.9% had an AP&OP prescription; uUGG episodes were more frequent with IA/SO (n=2386) than AP&OP (n=714) prescriptions during follow-up. Patients with IA/SO prescriptions had higher GC-related total adjusted costs per patient (PP) per index episode (&196) vs those with AP&OP prescriptions (&124, p < 0.0001; Figure). Patients with IA/SO prescriptions also had higher GCrelated total adjusted costs PP during follow-up (&220) vs those with AP&OP prescriptions (&148, p < 0.0001), mostly driven by higher outpatient ambulatory and emergency room (ER) adjusted costs with IA/SO (&148 and &71, respectively) vs AP&OP prescriptions (&129 and &12, respectively, p ≤ 0.0152; Figure). ER visits PP at index and during follow-up were higher with IA/SO vs AP&OP prescriptions (p < 0.0001; Table 2).Figure. GC-related costs per patient with uUGG, stratified by appropriateness of AB prescription* Table 2. GC-related HRU per patient with uUGG, stratified by AB prescription ConclusionMost patients with uUGG were not prescribed treatments in accordance with CDC 2015 guidelines. High IA/SO AB prescriptions and associated healthcare costs suggest an unmet need for improved prescribing practices for uUGG in the US.Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Ziyu Lan, MSc, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)