Molecular investigation of Treponema pallidum strains associated with ocular syphilis in the United States, 2016-2020.

Ocular syphilis is a serious complication of Treponema pallidum infection that can occur at any stage of syphilis and affect any eye structure. It remains unknown if certain T. pallidum strains are associated with ocular infections; therefore, we performed genotyping and whole genome sequencing (WGS) to characterize strains from patients with ocular syphilis. Seventy-five ocular or non-ocular specimens from 55 ocular syphilis patients in 14 states within the United States were collected between February 2016 and November 2020. Sufficient T. pallidum DNA was available from nine patients for genotyping and three for WGS. Genotyping was done using the augmented Centers for Disease Control and Prevention typing scheme, and WGS was performed on Illumina platforms. Multilocus sequence typing allelic profiles were predicted from whole genome sequence data. T. pallidum DNA was detected in various specimens from 17 (30.9%) of the 55 patients, and typing was done on samples from 9 patients. Four complete strain types (14d10/g, 14b9/g, 14d9/g, and 14e9/f) and five partial types were identified. WGS was successful on samples from three patients and all three strains belonged to the SS14 clade of T. pallidum. Our data reveal that multiple strain types are associated with ocular manifestations of syphilis. While genotyping and WGS were challenging due to low amounts of T. pallidum DNA in specimens, we successfully performed WGS on cerebrospinal fluid, vitreous fluid, and whole blood.IMPORTANCESyphilis is caused by the spirochete Treponema pallidum. Total syphilis rates have increased significantly over the past two decades in the United States, and the disease remains a public health concern. In addition, ocular syphilis cases has also been on the rise, coinciding with the overall increase in syphilis rates. We conducted a molecular investigation utilizing traditional genotyping and whole genome sequencing over a 5-year period to ascertain if specific T. pallidum strains are associated with ocular syphilis. Genotyping and phylogenetic analysis show that multiple T. pallidum strain types are associated with ocular syphilis in the United States.

CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024.

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.

Early Tecovirimat Treatment for Mpox Disease Among People With HIV.

Importance: Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations. Objective: To evaluate if PWH with mpox who were treated with tecovirimat within 7 days of symptom onset were less likely to have mpox disease progression. Design, Setting, and Participants: This cohort study included PWH diagnosed with mpox at 4 hospitals in Atlanta, Georgia, between June 1 and October 7, 2022. Patients were grouped according to whether they were treated with tecovirimat within 7 days of mpox symptom onset (early tecovirimat cohort) or they did not receive tecovirimat or received the drug 7 or more days after symptom onset (late or no tecovirimat cohort). Multivariable logistic regression models were used to identify factors associated with progression of mpox disease. The 2 cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared. Exposures: Treatment with tecovirimat within 7 days of mpox symptom onset. Main Outcome and Measures: Progression of mpox disease, defined as the development of at least 1 severe mpox criterion established by the US Centers for Disease Control and Prevention, after symptom day 7. Results: After propensity score matching, a total of 112 PWH were included in the analysis; 56 received tecovirimat within 7 days of mpox symptom onset (early tecovirimat group) and 56 were either treated later or did not receive tecovirimat (late or no tecovirimat group). In the early tecovirimat group, the median (IQR) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black individuals, and 10 (17.9%) were individuals of other races (American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or White) or unknown race. In the late or no tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black individuals, and 7 (12.5%) were individuals of other races or unknown race. Mpox disease progression occurred in 3 PWH (5.4%) in the early tecovirimat group and in 15 PWH (26.8%) in the late or no tecovirimat group (paired odds ratio, 13.00 [95% CI, 1.71-99.40]; P = .002). Conclusion and Relevance: Results of this cohort study support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is warranted to confirm these findings.

Diagnosis and Management of Trichomonas vaginalis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

Evaluation of HIV-1 reservoir size and broadly neutralizing antibody susceptibility in acute antiretroviral therapy-treated individuals.

OBJECTIVE: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. METHODS: Four cohorts with participants who initiated ART during acute infection or during chronic infection were enrolled in a cross-sectional, noninterventional study. Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIV DNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. RESULTS: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. CONCLUSION: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.

Sexually Transmitted Infections Treatment Guidelines, 2021.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.

Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020.

Sexually transmitted infections (STIs) caused by the bacteria Neisseria gonorrhoeae (gonococcal infections) have increased 63% since 2014 and are a cause of sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility and can facilitate transmission of human immunodeficiency virus (HIV) (1,2). Effective treatment can prevent complications and transmission, but N. gonorrhoeae's ability to acquire antimicrobial resistance influences treatment recommendations and complicates control (3). In 2010, CDC recommended a single 250 mg intramuscular (IM) dose of ceftriaxone and a single 1 g oral dose of azithromycin for treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum as a strategy for preventing ceftriaxone resistance and treating possible coinfection with Chlamydia trachomatis (4). Increasing concern for antimicrobial stewardship and the potential impact of dual therapy on commensal organisms and concurrent pathogens (3), in conjunction with the continued low incidence of ceftriaxone resistance and the increased incidence of azithromycin resistance, has led to reevaluation of this recommendation. This report, which updates previous guidelines (5), recommends a single 500 mg IM dose of ceftriaxone for treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydial infection has not been excluded, concurrent treatment with doxycycline (100 mg orally twice a day for 7 days) is recommended. Continuing to monitor for emergence of ceftriaxone resistance through surveillance and health care providers' reporting of treatment failures is essential to ensuring continued efficacy of recommended regimens.

Evidence Review for Centers for Disease Control and Prevention Guidance Development on Laboratory Testing to Detect Treponema pallidum Infection (Syphilis).

The articles in this supplement address key questions on syphilis diagnostics, provide reference tables of test performances, and discuss optimal specimens and knowledge gaps. Laboratory-developed genetic direct detection tests could be most useful at the point of care and add to the currently available serologic methods of nontreponemal and treponemal tests.

Evaluation of the National Sexually Transmitted Disease Curriculum: Reach, Utilization, and Engagement.

BACKGROUND: With increasing rates of sexually transmitted infections in the United States, there is a critical need to educate health professionals on the prevention, diagnosis, and treatment of sexually transmitted infections. The National Sexually Transmitted Disease Curriculum (NSTDC, https://www.std.uw.edu) is a free, online curriculum, funded by the Centers for Disease Control and Prevention. The purpose of this article is to evaluate the reach, utilization, and engagement of users with the curriculum. METHODS: Data on NSTDC utilization was collected for 24 months after the February 1, 2017 launch. For all users, Google Analytics was used to determine total number of users, geographic location, age and sex, and average session duration. For registered users, additional data analysis included work-role, demographics, and completion of self-study modules, check-on-learning questions, and question banks. User satisfaction was measured on a 5-point Likert scale. RESULTS: During the evaluation period, 136,270 individual users accessed the NSTDC, including 24,652 registered users. Among all registered users, 10,660 (43.2%) were registered nurses, 2810 (11.4%) physicians, 4942 (20.1%) Advanced Practice Nurses and Physician Assistants, and 6213 (25.2%) nonclinicians. Among registered users, 18,533 (75.2%) completed at least 1 module, 7898 (32.0%) completed all 7 modules, and 19,804 (80.4%) answered optional check-on-learning questions. Median satisfaction with the content was (5) very satisfied (interquartile range, 4-5). CONCLUSIONS: The NSTDC is a free, guideline-based, online curriculum with novel dual functionality that has achieved extensive reach with a broad array of health professionals who engage deeply with the material. The wide usage of NSTDC demonstrates the need for high-quality, unbiased, free content in user-focused formats.

Trichomonas vaginalis in Pregnancy: Patterns and Predictors of Testing, Infection, and Treatment.

OBJECTIVE: To identify factors associated with testing for and diagnosis of trichomoniasis in pregnancy and to describe patterns of treatment and tests of reinfection or persistence. METHODS: We conducted a retrospective cohort study of women who delivered from July 2016 to June 2018 at one institution. Testing for Trichomonas vaginalis infection was done by wet mount microscopy or by nucleic acid amplification testing for routine prenatal testing or symptomatic visits. Poisson regression was used to identify factors associated with testing for trichomoniasis and testing positive in pregnancy. Treatment and re-testing patterns also were assessed. RESULTS: Among 3,265 pregnant women, 2,489 (76%) were tested for T vaginalis infection. Of the total sample, 1,808 (55%) were tested by wet mount microscopy, 1,661 (51%) by nucleic acid amplification testing, and 980 (30%) by both modalities. The sensitivity for microscopy compared with nucleic acid amplification testing was 26%, with a specificity of 99%. Factors associated with increased likelihood of being tested included younger age (adjusted risk ratio [aRR] 0.99, 95% CI 0.99-1.00) and bacterial vaginosis (aRR 1.17, 95% CI 1.01-1.37). Prevalence of trichomoniasis was 15% among those tested by any modality (wet mount or nucleic acid amplification testing). Risk factors for trichomoniasis included younger age (aRR 0.97, P<.01), being of black race (aRR 2.62, P<.01), abnormal vaginal discharge (aRR 1.45, P<.01), and chlamydia during the current pregnancy (aRR 1.70, P<.01). Women diagnosed by microscopy had a shorter time to treatment compared with those diagnosed by nucleic acid amplification testing. Most (75%) women with positive infections had a test of reinfection; 29% of these were positive. Bacterial vaginosis was associated with decreased risk of a positive test of reinfection. CONCLUSION: Although testing for and treatment of trichomoniasis during pregnancy is not routinely recommended, the high burden of infection among some pregnant women demonstrates a need to further understand patterns of T vaginalis testing and infection. Opportunities exist for improving timely treatment of trichomoniasis and test of reinfection.

Successful isolation of Treponema pallidum strains from patients' cryopreserved ulcer exudate using the rabbit model.

Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation.

Recommendations for Providing Quality Sexually Transmitted Diseases Clinical Services, 2020.

This report (hereafter referred to as STD QCS) provides CDC recommendations to U.S. health care providers regarding quality clinical services for sexually transmitted diseases (STDs) for primary care and STD specialty care settings. These recommendations complement CDC's Sexually Transmitted Diseases Treatment Guidelines, 2015 (hereafter referred to as the STD Guidelines), a comprehensive, evidence-based reference for prevention, diagnosis, and treatment of STDs. STD QCS differs from the STD Guidelines by specifying operational determinants of quality services in different types of clinical settings, describing on-site treatment and partner services, and indicating when STD-related conditions should be managed through consultation with or referral to a specialist. These recommendations might also help in the development of clinic-level policies (e.g., standing orders, express visits, specimen panels, and reflex testing) that can facilitate implementation of the STD Guidelines. CDC organized the recommendations for STD QCS into eight sections: 1) sexual history and physical examination, 2) prevention, 3) screening, 4) partner services, 5) evaluation of STD-related conditions, 6) laboratory, 7) treatment, and 8) referral to a specialist for complex STD or STD-related conditions.CDC developed the recommendations by synthesizing relevant, evidence-based guidelines and recommendations issued by other experts; reviewing current practice in the United States; soliciting Delphi ratings by subject matter experts on STD care in primary care and STD specialty care settings; discussing the scientific evidence supporting the proposed recommendations at a consultation meeting of experts and institutional stakeholders held November 20, 2015, in Atlanta, Georgia; conducting peer reviews of draft recommendations and supporting evidence; and discussing draft recommendations and supporting evidence during meetings of the CDC/Health Resources and Services Administration Advisory Committee on HIV, Viral Hepatitis, and STD Prevention and Treatment STD Work Group. These recommendations are intended to help health care providers in primary care or STD specialty care settings offer STD services at their clinical settings and to help the persons seeking care live safer, healthier lives by preventing and treating STDs and related complications.

Efficacy and Safety of Single-Dose Oral Delafloxacin Compared With Intramuscular Ceftriaxone for Uncomplicated Gonorrhea Treatment: An Open-Label, Noninferiority, Phase 3, Multicenter, Randomized Study.

BACKGROUND: We evaluated single oral dose of delafloxacin versus single intramuscular ceftriaxone in participants with uncomplicated urogenital gonorrhea (primary objective). Secondary objectives included the efficacy, safety, and tolerability of delafloxacin versus ceftriaxone for uncomplicated urogenital, rectal, and/or pharyngeal gonorrhea. METHODS: In this open-label, multicenter study, 460 participants at 25 study centers were randomized (2:1) to receive a single 900-mg oral dose of delafloxacin or 250-mg intramuscular ceftriaxone. Neisseria gonorrhoeae culture, nucleic acid amplification test, and clinical responses were evaluated. The primary efficacy end point was the urogenital microbiological cure in the urogenital microbiological intention-to-treat population; noninferiority (NI) was assessed using a 10% NI margin. RESULTS: In the urogenital microbiological intention-to-treat population, urogenital cure rates for delafloxacin were 85.1% (194/228) versus 91.0% (91/100) for ceftriaxone (95% confidence interval, -13.18% to 1.36%). Because the lower bound of the confidence interval exceeded the prespecified -10% NI margin, delafloxacin did not demonstrate NI to ceftriaxone. Treatment failures were more often associated with N. gonorrhoeae with higher delafloxacin minimum inhibitory concentration (MIC) values. In microbiologically evaluable participants, failure occurred in 1 (0.6%) of 177 urogenital infections caused by isolates with delafloxacin MICs <0.008 µg/mL and 31 (64.6%) of 48 infections caused by isolates with delafloxacin MICs ≥0.008 µg/mL. Gastrointestinal adverse events were common with 900-mg of delafloxacin and typically included mild to moderate diarrhea, flatulence, nausea, and vomiting. The most common adverse event was diarrhea in both treatment groups. CONCLUSIONS: A single 900-mg dose of delafloxacin is not a reliable treatment of uncomplicated urogenital gonorrhea. Treatment failures were common in infections caused by N. gonorrhoeae with delafloxacin MICs ≥0.008 µg/mL. Additional testing with alternative dosing regimens could be considered.ClinicalTrials.gov Identifier: NCT02015637.

Combined Intravitreal and Systemic Antibiotic Therapy in a Patient with Syphilitic Uveitis.

PURPOSE: To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis. METHODS: Case report Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1 month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. The patient denied history of genital lesions or rash, but did complain of difficulty hearing bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512 dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was made based on the clinical and laboratory findings. The patient was admitted for systemic intravenous antibiotic therapy, but was noted to have a penicillin allergy. Intravitreal ceftazidime was promptly administered bilaterally to achieve treponemacidal levels of antibiotic therapy. After penicillin desensitization protocol, the patient received 14 days of intravenous penicillin with clinical resolution. CONCLUSIONS: There are increasing reports of ocular syphilis in the United States and delay in diagnosis and management can lead to severe visual impairment and blindness. We report the first case of adjunct intravitreal antibiotic therapy in a penicillin allergic patient. As ocular syphilis is a form of bacterial endophthalmitis, combination intravitreal and systemic antibiotics may be considered.

Survey of Obstetrician-gynecologists in the United States About Trichomoniasis, 2016.

PURPOSE: Trichomoniasis is the most prevalent nonviral sexually transmitted infection (STI) in the United States. It can present with vaginitis in women and urethritis in men, but is most often asymptomatic or occurs with minimal symptoms. It is associated with other STIs, adverse pregnancy outcomes and pelvic inflammatory disease. For these reasons, health care provider awareness of trichomoniasis is of public health importance. METHODS: To assess practitioner knowledge, attitudes, and practices concerning trichomoniasis management, the American College of Obstetricians and Gynecologists conducted an online survey in 2016 of its members, and we analyzed results from 230 respondents. RESULTS: We note discrepancies between practice and recommendations among surveyed providers: a minority of respondents routinely screen human immunodeficiency virus (HIV)-positive patients for trichomoniasis (10.7%, "most of the time"; 95% confidence interval [CI], 6.7-15.8; 33.0%, "always"; 95% CI, 26.5%-40.0%), treat trichomoniasis in HIV-positive patients with the recommended dose of metronidazole 500 mg twice a day for 7 days (25.8%; 95% CI, 20.0%-32.3%), or retest patients diagnosed with trichomoniasis 3 months after treatment (9.6%; 95% CI, 6.1%-14.3%). Only 29.0% (95% CI, 23.0%-35.5%) retreat with metronidazole 500 mg twice a day for 7 days in patients who have failed prior treatment. CONCLUSIONS: Screening for and treatment of trichomoniasis in HIV-positive patients, and retesting and retreatment for trichomoniasis in the general population appear to be suboptimal. Continuing education for providers is needed for this common but "neglected" STI.

Gepotidacin for the Treatment of Uncomplicated Urogenital Gonorrhea: A Phase 2, Randomized, Dose-Ranging, Single-Oral Dose Evaluation.

Background: In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea. Methods: Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4-8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results: The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose. Conclusions: This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration: NCT02294682.