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A vaginal panel assay could improve diagnostic accuracy for vaginitis and facilitate appropriate and timely treatment., OBJECTIVE: To compare the performance of vaginitis diagnosis based on clinical assessment to molecular detection of organisms associated with bacterial vaginosis, vulvovaginal candidiasis, and Trichomonas vaginalis using a vaginal panel assay. METHODS: This cross-sectional diagnostic accuracy study included 489 enrolled participants from five collection sites where those with vaginitis symptoms had a vaginal assay swab collected during their visit and a clinical diagnosis made. The swab was later sent to a separate testing site to perform the vaginal panel assay. Outcome measures include positive, negative, and overall percent agreement (and accompanying 95% CIs) of clinical assessment with the vaginal panel assay. P

Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded before enrollment because of bacterial sexually transmitted infection coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) was common. Study findings highlight the need for comprehensive bacterial sexually transmitted infection screening in patients with syphilis.

Prospective cohort studies of sexually transmitted infections (STIs) are logistically impractical owing to time and expenses. In schools, students are readily available for school-related follow-ups and monitoring. Capitalizing on the logistics that society already commits to ensure regular attendance of adolescents in school, a school-based STI screening in New Orleans made it possible to naturally observe the occurrence of chlamydia and to determine its incidence among 14-19-year-old adolescents. Among participants screened repeatedly, we calculated incidence rates, cumulative incidence, and incidence times. Male (n = 3820) and female (n = 3501) students were observed for 6251 and 5143 person-years, respectively, during which 415 boys and 610 girls acquired chlamydia. Incidence rates per 100 person-years were 6.6 cases for boys and 11.9 cases for girls. In multivariable analysis, the adjusted hazard ratio was 5.34 for boys and 3.68 for girls if the student tested positive for gonorrhea during follow-up, and 2.76 for boys and 1.59 for girls if at first participation the student tested positive for chlamydia, and it increased with age among boys but not among girls. In joinpoint trend analysis, the annual percentage change in the incidence rate was 6.6% for boys (95% CI: -1.2%, 15.1%) and 0.1% for girls (95% CI: -5.3%, 5.7%). Annual cumulative incidence was 5.5% among boys and 8.6% among girls. Median incidence time was 9.7 months for boys and 6.9 months for girls. Our findings can be used to refine assumptions in mathematical modeling and in cost analysis studies of

Specialised sexual health clinics (SHCs) play an important role in addressing the staggering rates of STIs seen in many high-income nations. Despite increasing healthcare coverage in the US and nationalised health care in some countries, there is a continued need for SHCs to meet the needs of patients and the community, especially for high-priority populations: those at high risk of STI acquisition and/or groups historically marginalised and underserved in the traditional healthcare system. We need to mobilise resources to support a stronger clinical infrastructure in specialised SHCs. This review describes the importance of SHCs, their future role, and some of the innovative programs housed within SHCs in the US, Australia, and the Netherlands to address both STI and HIV prevention for the populations they serve.

A study including female and male participants across 12 US clinics found that a triplex assay, BD CTGCTV2, performed on the benchtop BD MAX instrument, shows good performance for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Supplemental digital content is available in the text., Background Diagnostic options to combat the increasing rates of sexually transmitted infections recorded throughout the world increasingly include multiplex assays. Here we describe the estimated sensitivity and specificity of a triplex molecular assay that simultaneously detects Chlamydia trachomatis (CT), Neisseria gonorrhoeae (or gonococci [GC]), and Trichomonas vaginalis (TV). Methods Participants (2547 women and 1159 men) were recruited from 12 clinics in the United States. BD CTGCTV2 for BD MAX System assay (CTGCTV2) results were obtained from vaginal and endocervical swabs, endocervical samples in cytology medium, and female and male urine. Results were compared with infection standards that were sample type and pathogen dependent. Results Female specimen sensitivity estimates ranged from 92.7% to 98.4%, 92.9% to 100%, and 86.6% to 100% for CT, GC and TV, respectively. Male urine sensitivity estimates were 96.7%, 99.2%, and 97.9% for CT, GC, and TV, respectively. Specificity estimates were >98.7% for all sample types. Conclusions BD CTGCTV2 performed well using a variety of sample types. As a true triplex assay, performed using a benchtop instrument, BD CTGCTV2 may be useful in settings where no testing is currently performed and in settings, such as reference laboratories, where testing turnaround time may be several days. Use of this assay at local laboratories may result in greater access to testing and a shorter time to result, which are important steps for improving our ability to combat sexually transmitted infections.

Background Antimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the United States or about its associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and posttreatment symptom persistence. Methods We enrolled men presenting with urethritis symptoms to 6 US sexually transmitted disease (STD) clinics during June 2017–July 2018; men with urethritis were eligible for follow-up contact and, if they had persistent symptoms or MG, a chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S ribosomal ribonucleic acid (rRNA) loci (macrolide resistance–associated mutations [MRMs]) and in parC and gyrA (quinolone-associated mutations) were detected by targeted amplification/Sanger sequencing. Results Among 914 evaluable participants, 28.7% (95% confidence interval [CI], 23.8–33.6) had MG. Men with MG were more often Black (79.8% vs 66%, respectively), Conclusions MG infection was common among men with urethritis; the MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men both with and without MG.

Research using nucleic acid amplification tests (NAATs) have repeatedly found rectal and oropharyngeal infections with Chlamydia trachomatis and Neisseria gonorrhoeae to be common and potentially more difficult to treat than genital infections. Unfortunately, public health and patient care efforts have been hampered by the lack of FDA-cleared NAATs with claims for anorectal or oropharyngeal samples. At the time of the initiation of this study, no commercially available assays had these claims. We formed a novel partnership among academic institutions and diagnostic manufacturers to address this public health need. From May 2018 through August 2019, we recruited 1108 women, 1256 men, and 26 transgender persons each of whom provided 3 anal and 3 oropharyngeal swab specimens. The 3 anal swabs were pooled into a single transport tube as were the 3 oropharyngeal swabs. The performance of each of three study assays was estimated by comparison to the composite result and relative to one another. Percent positivity for chlamydia was 5.9 and 1.2% from anal and oropharyngeal specimens, respectively, compared to 4.2 and 4.1% for gonorrhea. Sensitivity for chlamydia detection ranged from 81.0 to 95.1% and 82.8 to 100% for anal and oropharyngeal specimens, respectively. Gonorrhea sensitivity ranged from 85.9 to 99.0% and 74.0 to 100% for anal and oropharyngeal samples, respectively. Specificity estimates were ≥ 98.9% for all assays, organisms, and sample types. Although there was heterogeneity between sensitivity estimates, these assays offer better ability to detect extragenital infections than culture and potential solutions for providing appropriate sexual health care for populations in which these infections are of concern.

Summary Background Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. Methods We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov , NCT04492475 . Findings Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87–1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3–7%) in the interferon beta-1a plus remdesivir group and 3% (2–6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69–2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. Interpretation Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. Funding The National Institute of Allergy and Infectious Diseases (USA).

BACKGROUND We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through the Centers for Disease Control and Prevention's enhanced Gonococcal Isolate Surveillance Project and Strengthening the US Response to Resistant Gonorrhea. METHODS During the period January 1, 2018-December 31, 2019, 12 enhanced Gonococcal Isolate Surveillance Project and 8 Strengthening the US Response to Resistant Gonorrhea sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in sexually transmitted disease clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs), and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS Participating clinics collected 3974 urethral, 1553 rectal, and 1049 pharyngeal isolates from 5456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared with anogenital isolates (P < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 μg/mL) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (P < 0.05). CONCLUSIONS Based on data collected from multijurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of Neisseria gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

Innovative delivery strategies are needed to facilitate access to HIV pre-exposure prophylaxis (PrEP). The objective of this study was to evaluate a navigator-facilitated PrEP referral process from a sexual health center (SHC) to a co-located PrEP clinic as an alternative delivery model. Electronic health record (EHR) data were used to calculate the number of clients seen at the SHC in 2019. Charts were manually reviewed to determine whether a PrEP clinic referral was made and document type of referral method: face-to-face appointment scheduling with the navigator (warm handoff), EHR messaging to navigator to schedule the appointment at a later time (EHR message), or provision of navigator's contact information to the client (card only). In 2019, 2481 unique potentially PrEP-eligible clients were seen at the SHC; 220 (9%) received a PrEP referral. Of referred clients, median age was 30 years (interquartile range, 24-34), 182 (83%) were male, 89 (40%) were non-Hispanic Black, and 24 (11%) were Latinx. In total, 94/220 (43%) referred clients attended an initial PrEP visit with a provider, and the proportion attending by referral method was 81%, 36%, and 27% for warm handoff, EHR message, and card only, respectively (p

Trichomonas vaginalis is a prevalent sexually transmitted infection (STI). Diagnosis has historically relied on either microscopic analysis or culture, the latter being the previous gold standard. However, these tests are not readily available for male diagnosis, generally only perform well for symptomatic women, and are not as sensitive as nucleic acid amplification tests (NAATs). Men are largely asymptomatic but carry the organism and transmit to their sexual partners. This multicenter, prospective study evaluated the performance of the cobas T. vaginalis/Mycoplasma genitalium (TV/MG) assay for detection of T. vaginalis DNA compared with patient infection status (PIS) defined by a combination of commercially available NAATs and culture using urogenital specimens. A total of 2,064 subjects (984 men and 1,080 women, 940 [45.5%] symptomatic, 1,124 [54.5%] asymptomatic) were evaluable. In women, sensitivity ranged from 99.4% (95% confidence interval [CI] 96.8 to 99.9%) using vaginal samples to 94.7% (95% CI 90.2 to 97.2%) in PreservCyt samples. Specificity ranged from 98.9 to 96.8% (95% CI 95.4 to 97.8%). In men, the cobas TV/MG assay was 100% sensitive for the detection of T. vaginalis in both male urine samples and meatal swabs, with specificity of 98.4% in urine samples and 92.5% in meatal swabs. The cobas TV/MG is a suitable diagnostic test for the detection of T. vaginalis, which could support public health efforts toward infection control and complement existing STI programs.

Background Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. Methods Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5–10 days post-treatment. Results Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5–100%). Conclusions Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. Clinical Trials Registration NCT02961751.

Gonorrhea remains a major public health challenge, and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetic and pharmacodynamic contributors to effective therapy, the prevention of antimicrobial resistance, and newer designs for clinical trials. They are hampered by the requirement to utilize combination ceftriaxone/azithromycin therapy as the comparator regimen in noninferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints hinder the enrollment of those populations at the greatest risk for gonorrhea (adolescents, women, and persons infected with antibiotic-resistant Neisseria gonorrhoeae). This article summarizes a recent meeting on the evaluation process for antimicrobials for urogenital gonorrhea treatment and encourages the consideration of new designs for the evaluation of gonorrhea therapy.

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.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.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 MICs0.008 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.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.

Background: Here we compare the performance of the high-throughput BD COR System (COR) to the Viper LT System (Viper) using the BD Onclarity HPV assay. Research Design and Methods: Remnant clinical specimens, contrived specimens in SurePath (BD) and PreservCyt (Hologic) media, and prospective clinical specimens in BD Cervical Brush Diluent (CBD) were tested. Outcomes included intra-laboratory agreement of Onclarity results on COR and inter-system agreement between COR and Viper. Results: Onclarity reproducibility on COR resulted in standard deviation and correlation of variation of Ct values ranging from 0.14 to 1.98 and 0.49% to 2.15%, respectively, for contrived specimens, and 0.9–3.08 and 2.89–9.21%, respectively, for clinical specimens. In the COR and Viper clinical agreement study, OPA for Onclarity ranged from 97.1%-98.9%, depending on the collection media type. PPA values for pooled, HPV(+) specimens at low positive (C95), and moderate positive (3XC95) target concentrations were ≥95.0% and 100%, respectively; PPA values associated with HPV 16, 18, 31, 45, 33/58, 52, 35/39/68, 51, and 56/59/66, individually, ranged from 93.8%-100%. Conclusions: Onclarity performance on COR is equivalent to Viper, and is accurate and reproducible for detection of all high-risk HPV genotypes, with a throughput of 330 results from a single 8-hour shift.

The clinical performance of the BD Veritor System for Rapid Detection of SARS-CoV-2 nucleocapsid antigen (Veritor), a chromatographic immunoassay used for SARS-CoV-2 point-of-care testing, was evaluated using nasal specimens from individuals with COVID-19 symptoms. Two studies were completed to determine clinical performance. In the first study, nasal specimens and either nasopharyngeal or oropharyngeal specimens from 251 participants with COVID-19 symptoms (≤7 days from symptom onset [DSO], ≥18 years of age) were utilized to compare Veritor with the Lyra SARS-CoV-2 PCR assay (Lyra). In the second study, nasal specimens from 361 participants with COVID-19 symptoms (≤5 DSO, ≥18 years of age) were utilized to compare performance of Veritor to that of the Sofia 2 SARS Antigen FIA test (Sofia 2). The positive, negative, and overall percent agreement (PPA, NPA, and OPA, respectively) were the primary outcomes. In study 1, the PPA for Veritor, compared to Lyra, ranged from 81.8 to 87.5% across the 0 to 1 and 0 to 6 DSO ranges. In study 2, Veritor had PPA, NPA, and OPA values of 97.4, 98.1, and 98.1%, respectively, with Sofia 2. Discordant analysis showed one Lyra positive missed by Veritor and five Lyra positives missed by Sofia 2; one Veritor positive result was negative by Lyra. Veritor met FDA emergency use authorization (EUA) acceptance criteria for SARS-CoV-2 antigen testing for the 0 to 5 and 0 to 6 DSO ranges (PPA values of 83.9% and 82.4%, respectively). Veritor and Sofia 2 showed a high degree of agreement for SARS-CoV-2 detection. The Veritor test allows for more rapid COVID-19 testing utilizing easy-to-collect nasal swabs but demonstrated

The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV., The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV. Finally, specimens were collected using either the Cervex-Brush or Cytobrush (or Cytobrush/spatula) for comparison of HPV results. Contrived specimens showed >95% concordance with the expected results, and pooled clinical specimens had standard deviations and coefficients of variation ranging from 0.87 to 1.86 and 2.9% to 5.6%, respectively. For precytology and postcytology aliquot analyses, specimens showed >98.0% overall agreement and mean differences in cycle threshold (CT) scores for HPV ranging from −0.07 to 0.31. Positivity rates were close between the Cervex-Brush and Cytobrush/spatula for all age groups tested. Onclarity results are reproducible and reliable, regardless of sample collection before or after cytology aliquoting. Onclarity performs well regardless of the method of specimen collection (Cervex-Brush or Cytobrush/spatula) for cervical cancer screening.

The clinical performance of the BD Veritor System for Rapid Detection of SARS-CoV-2 nucleocapsid antigen (Veritor), a chromatographic immunoassay used for SARS-CoV-2 point-of-care testing, was evaluated using nasal specimens from individuals with COVID-19 symptoms. Two studies were completed to determine clinical performance. In the first study, nasal specimens and either nasopharyngeal or oropharyngeal specimens from 251 participants with COVID-19 symptoms (≤7 days from symptom onset [DSO], ≥18 years of age) were utilized to compare Veritor with the Lyra SARS-CoV-2 PCR assay (Lyra). In the second study, nasal specimens from 361 participants with COVID-19 symptoms (≤5 DSO, ≥18 years of age) were utilized to compare performance of Veritor to that of the Sofia 2 SARS Antigen FIA test (Sofia 2). The positive, negative, and overall percent agreement (PPA, NPA, and OPA, respectively) were the primary outcomes. In study 1, the PPA for Veritor, compared to Lyra, ranged from 81.8 to 87.5% across the 0 to 1 and 0 to 6 DSO ranges. In study 2, Veritor had PPA, NPA, and OPA values of 97.4, 98.1, and 98.1%, respectively, with Sofia 2. Discordant analysis showed one Lyra positive missed by Veritor and five Lyra positives missed by Sofia 2; one Veritor positive result was negative by Lyra. Veritor met FDA emergency use authorization (EUA) acceptance criteria for SARS-CoV-2 antigen testing for the 0 to 5 and 0 to 6 DSO ranges (PPA values of 83.9% and 82.4%, respectively). Veritor and Sofia 2 showed a high degree of agreement for SARS-CoV-2 detection. The Veritor test allows for more rapid COVID-19 testing utilizing easy-to-collect nasal swabs but demonstrated100% PPA compared to PCR.

ObjectivesThe clinical performance of the BD Veritor™ System for Rapid Detection of SARS-CoV-2 antigen (Veritor), a chromatographic immunoassay that detects the SARS-CoV-2 nucleocapsid antigen as a point-of-care test, was evaluated on nasal specimens from individuals with COVID-19 symptoms.Methods and MaterialsTwo studies were completed to determine clinical performance. In the first study, nasal specimens and either nasopharyngeal or oropharyngeal specimens from 251 participants with COVID-19 symptoms (≤7 days from symptom onset [DSO]), ≥18 years of age, were utilized to compare Veritor with the Lyra®SARS-CoV-2 PCR Assay (Lyra). In the second study, nasal specimens from 361 participants with COVID-19 symptoms (≤5 DSO), ≥18 years of age, were utilized to compare performance of Veritor to that of the Sofia®2 SARS Antigen FIA test (Sofia 2). Positive, negative, and overall percent agreement (PPA, NPA, and OPA, respectively) were the primary outcomes.ResultsIn study 1, PPA for Veritor, compared to Lyra, ranged from 81.8%-87.5% for 0-1 through 0-6 DSO ranges. In study 2, Veritor had a PPA, NPA, and OPA of 97.4%, 98.1%, and 98.1%, respectively, with Sofia 2. Discordant analysis showed one Lyra positive missed by Veritor and five Lyra positives missed by Sofia 2; one Veritor positive result was negative by Lyra.ConclusionsVeritor met FDA-EUA acceptance criteria for SARS-CoV-2 antigen testing (≥80% PPA point estimate) for the 0-5 and 0-6 DSO ranges. Veritor and Sofia 2 showed a high degree of agreement for SARS-CoV-2 detection. The Veritor test should facilitate rapid and reliable results for COVID-19 diagnosis utilizing easy-to-collect nasal swabs.SummaryThe BD Veritor SARS-CoV-2 antigen test met FDA-EUA acceptance criteria for SARS-CoV-2 antigen testing for subjects with COVID-19 symptoms (0-5 days post-onset). BD Veritor and Quidel Sofia 2 antigen tests had good agreement for SARS-CoV-2 detection; discordant analysis favored Veritor.

Data from a large prospective multicenter clinical validation study of a nucleic acid amplification in vitro diagnostic test for Mycoplasma genitalium were analyzed to describe the prevalence of M. genitalium infection, risk factors, and disease associations in female and male patients seeking care in diverse geographic regions of the United States. Among 1,737 female and 1,563 male participants, the overall prevalence of M. genitalium infection was 10., Data from a large prospective multicenter clinical validation study of a nucleic acid amplification in vitro diagnostic test for Mycoplasma genitalium were analyzed to describe the prevalence of M. genitalium infection, risk factors, and disease associations in female and male patients seeking care in diverse geographic regions of the United States. Among 1,737 female and 1,563 male participants, the overall prevalence of M. genitalium infection was 10.3% and was significantly higher in persons ages 15 to 24 years than in persons ages 35 to 39 years (for females, 19.8% versus 4.7% [odds ratio {OR} = 5.05; 95% confidence interval {CI} = 3.01 to 8.46]; for males, 16.5% versus 9.4% [OR = 1.91; 95% CI = 1.20 to 3.02]). The risk for M. genitalium infection was higher in black than in white participants (for females, 12.0% versus 6.8% [OR = 1.88; 95% CI = 1.30 to 2.72]; for males, 12.9% versus 6.9% [OR = 2.02; 95% CI = 1.38 to 2.96]) and higher in non-Hispanic than in Hispanic participants (for females, 11.2% versus 6.0% [OR = 1.97; 95% CI = 1.25 to 3.10]; for males, 11.6% versus 6.8% [OR = 1.80; 95% CI = 1.14 to 2.85]). Participants reporting urogenital symptoms had a significantly elevated risk of M. genitalium infection compared to that for asymptomatic individuals (for females, OR = 1.53 [95% CI = 1.09 to 2.14]; for males, OR = 1.42 [95% CI = 1.02 to 1.99]). Women diagnosed with vaginitis and cervicitis had a higher prevalence of M. genitalium infection than women without those diagnoses, although this was statistically significant only for vaginitis (for vaginitis, OR = 1.88 [95% CI = 1.37 to 2.58]; for cervicitis, OR = 1.42 [95% CI = 0.61 to 2.96]). A diagnosis of urethritis in men was also significantly associated with M. genitalium infection (OR = 2.97; 95% CI = 2.14 to 4.13). Few characteristics distinguished asymptomatic from symptomatic M. genitalium infections. These results from persons seeking care in the United States suggest that M. genitalium infection should be considered in young persons presenting with urogenital symptoms.

Mycoplasma genitalium (MG) infections are a growing concern within the field of sexually transmitted infections. However, diagnostic assays for M. genitalium have been limited in the United States. As most infections are asymptomatic, individuals can unknowingly pass the infection on, and the prevalence is likely to be underestimated. Diagnosis of M. genitalium infection is recommended using a nucleic acid test. This multicenter study assessed the performance of the cobas Trichomonas vaginalis (TV)/MG assay (cobas) for the detection of M. genitalium, using 22,150 urogenital specimens from both symptomatic and asymptomatic men and women collected at geographically diverse sites across the United States., Mycoplasma genitalium (MG) infections are a growing concern within the field of sexually transmitted infections. However, diagnostic assays for M. genitalium have been limited in the United States. As most infections are asymptomatic, individuals can unknowingly pass the infection on, and the prevalence is likely to be underestimated. Diagnosis of M. genitalium infection is recommended using a nucleic acid test. This multicenter study assessed the performance of the cobas Trichomonas vaginalis (TV)/MG assay (cobas) for the detection of M. genitalium, using 22,150 urogenital specimens from both symptomatic and asymptomatic men and women collected at geographically diverse sites across the United States. The performance was compared to a reference standard of three laboratory-developed tests (LDTs). The specificity of the cobas assay for M. genitalium ranged from 96.0% to 99.8% across symptomatic and asymptomatic men and women. The sensitivities in female vaginal swabs and urine samples were 96.6% (95% confidence interval [CI], 88.5 to 99.1%) and 86.4% (95% CI, 75.5 to 93.0%), respectively. The sensitivities in male urine and meatal swab samples were 100% (95% CI, 94.0 to 100%) and 85.0% (95% CI, 73.9 to 91.9%), respectively. This study demonstrated that the cobas assay was highly sensitive and specific in all relevant clinical samples for the detection of M. genitalium.

Infectious vaginitis due to bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis accounts for a significant proportion of all gynecologic visits in the United States. A prospective multicenter clinical study was conducted to validate the performance of two new in vitro diagnostic transcription-mediated amplification nucleic acid amplification tests (NAATs) for diagnosis of BV, VVC, and trichomoniasis., Infectious vaginitis due to bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis accounts for a significant proportion of all gynecologic visits in the United States. A prospective multicenter clinical study was conducted to validate the performance of two new in vitro diagnostic transcription-mediated amplification nucleic acid amplification tests (NAATs) for diagnosis of BV, VVC, and trichomoniasis. Patient- and clinician-collected vaginal-swab samples obtained from women with symptoms of vaginitis were tested with the Aptima BV and Aptima Candida/Trichomonas vaginitis (CV/TV) assays. The results were compared to Nugent (plus Amsel for intermediate Nugent) scores for BV, Candida cultures and DNA sequencing for VVC, and a composite of NAAT and culture for T. vaginalis. The prevalences of infection were similar for clinician- and patient-collected samples: 49% for BV, 29% for VVC due to the Candida species group, 4% for VVC due to Candida glabrata, and 10% for T. vaginalis. Sensitivity and specificity estimates for the investigational tests in clinician-collected samples were 95.0% and 89.6%, respectively, for BV; 91.7% and 94.9% for the Candida species group; 84.7% and 99.1% for C. glabrata; and 96.5% and 95.1% for T. vaginalis. Sensitivities and specificities were similar in patient-collected samples. In a secondary analysis, clinicians’ diagnoses, in-clinic assessments, and investigational-assay results were compared to gold standard reference methods. Overall, the investigational assays had higher sensitivity and specificity than clinicians’ diagnoses and in-clinic assessments, indicating that the investigational assays were more predictive of infection than traditional diagnostic methods. These results provide clinical-efficacy evidence for two in vitro diagnostic NAATs that can detect the main causes of vaginitis.

ObjectivesInfections due to Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are among the most common bacterial sexually transmitted infections worldwide, most of which are asymptomatic. Detection of infection using a variety of specimen types in symptomatic and asymptomatic subjects is important to effectively combat CT/NG infections. The performance of the cobas CT/NG v2.0 test was assessed for urogenital swabs, urine and cervical cytology samples collected in PreservCyt Solution from 5266 symptomatic and asymptomatic women (including 202 who were pregnant), and urine from 738 men.MethodsSensitivity and specificity were estimated compared with a patient infected status determined using two US Food and Drug Administration–cleared nucleic acid amplification tests.ResultsAmong 6004 participants, 487 CT (8.1%) and 159 NG (2.6%) infections were identified. Sensitivity estimates for CT for women ranged from 91.2% to 97.6% depending on specimen type, and the estimate for male urine specimens was 98.4%. Specificity for CT ranged from 99.2% to 99.7%. Sensitivity estimates for NG ranged from 95.6% to 100.0% for women, and the estimate for men was 100.0%. Specificity for NG ranged from 99.3% to 100.0%.ConclusionsThe cobas CT/NG v2.0 test performs well using urogenital swabs, urine and cervical samples collected in PreservCyt solution.

In this phase 2 study, single oral doses of gepotidacin were ≥95% effective for bacterial eradication in culture-proven uncomplicated urogenital gonorrhea. New antibiotics for drug-resistant Neisseria gonorrhoeae are urgently needed. With additional evaluation, gepotidacin may provide an alternative therapeutic option., 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.

Background Extragenital gonococcal infections are common among men who have sex with men (MSM); however, data comparing antimicrobial susceptibilities of urogenital and extragenital Neisseria gonorrhoeae isolates are limited. We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender MSM using specimens collected through CDC’s enhanced Gonococcal Isolate Surveillance Project (eGISP) and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). Methods During January 1, 2018–December 31, 2019, 12 eGISP and 8 SURRG sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in STD clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs) and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. Results Participating clinics collected 3,974 urethral, 1,553 rectal, and 1,049 pharyngeal isolates from 5,456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared to anogenital isolates (p< 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥ 0.125 µg/ml) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (p< 0.05). Conclusion Based on data collected from multi-jurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of N. gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time. Disclosures Olusegun O. Soge, PhD, Hologic Inc. (Grant/Research Support)SpeeDx Inc. (Grant/Research Support) Stephanie N. Taylor, MD, GARDP - GC Antibiotic Development (Scientific Research Study Investigator, To my institution.)GlaxoSmithKline (Grant/Research Support, Funds to my institution.)

The BD Max CT/GC/TV (MAX) assay is a true multiplex assay for simultaneous detection of chlamydia (CT), gonorrhea (GC), and trichomonas (TV). We evaluated assay performance for women using endocervical and vaginal swabs as well as urine specimens. A total of 1,143 women were tested for CT, GC, and TV and, subsequently, another 847 (1,990 total women) for CT and GC only, with positivity rates for CT, GC, and TV of 7.1%, 2.3%, and 13.5%, respectively. In men, the performance for CT and GC was determined using only urine specimens. TV performance was not assessed in male urine samples. Among men, 181/830 (21.8%) and 108/840 (12.9%) chlamydia and gonorrhea infections, respectively, were identified. Comparator assays included BD ProbeTec Chlamydia trachomatis Q x (CTQ)/ Neisseria gonorrhoeae Q x (GCQ), Hologic Aptima Combo 2 (AC2) and Aptima TV (ATV), trichomonas microscopy, and culture. MAX CT sensitivity was 99.3% (95% confidence interval [CI], 96.1% to 99.9%), 95.7% (90.8% to 98.0%), 91.5% (85.8% to 95.1%), and 96.1% (92.2% to 98.1%) for vaginal swabs, endocervical swabs, female urine samples, and male urine samples, respectively. MAX GC sensitivity was 95.5% (84.9% to 98.7%), 95.5% (84.9% to 98.7%), 95.7% (85.5% to 99.8%), and 99.1% (94.9% to 99.8%) in the same order. MAX TV sensitivity was 96.1% (91.7% to 98.2%) for vaginal swabs, 93.4% (88.3% to 96.4%) for endocervical swabs, and 92.9% (87.8% to 96.0%) for female urine samples. Specificity for all organisms across all sample types was ≥98.6%. Performance estimates for the MAX assays were consistent with estimates calculated for the comparator assays (all P values were >0.1). The availability of a CT/GC/TV multiplexed assay on a benchtop instrument with a broad menu has the potential to facilitate local sexually transmitted infection (STI) testing at smaller laboratories and may encourage expanded screening for these highly prevalent infections.

A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium., A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium. Seven urogenital specimen types (n = 11,556) obtained from 1,778 females, aged 15 to 74 years, and 1,583 males, aged 16 to 82 years, were tested with the Aptima Mycoplasma genitalium assay, an investigational transcription-mediated amplification (TMA) NAAT for the detection of M. genitalium 16S rRNA. Infected status for enrolled subjects was established using results obtained from testing either self-collected vaginal swab or clinician-collected male urethral swab specimens with a composite reference method consisting of three transcription-mediated amplification NAATs targeting unique regions of M. genitalium 16S or 23S rRNA. M. genitalium prevalence was 10.2% in females and 10.6% in males; prevalence was high in both symptomatic and asymptomatic subjects for both sexes. Compared to the subject infected status standard, the investigational test had sensitivity and specificity estimates, respectively, of 98.9% and 98.5% for subject-collected vaginal swabs, 92.0% and 98.0% for clinician-collected vaginal swabs, 81.5% and 98.3% for endocervical swabs, 77.8% and 99.0% for female urine, and 98.2% and 99.6% for male urethral swabs, 88.4% and 97.8% for self-collected penile meatal swabs, and 90.9% and 99.4% for male urine specimens. For all seven specimen types, within-specimen positive and negative agreements between the investigational test and the composite reference standard ranged from 94.2% to 98.3% and from 98.5 to 99.9%, respectively. These results provide clinical efficacy evidence for the first FDA-cleared NAAT for M. genitalium detection in the United States.

Background Mycoplasma genitalium (MG) is an emerging cause of urethritis. Although an FDA-approved MG diagnostic test is now available in the U.S., syndromic management of urethritis remains widespread. Little is known about the geographic distribution of MG resistance in the U.S. and associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, antimicrobial susceptibility of MG, and post-treatment symptom persistence. Methods We enrolled men presenting with urethritis symptoms to 6 U.S. STD clinics during June 2017–July 2018. Participants with urethritis confirmed on stained urethral smear were eligible for a follow-up phone call 14–17 days post-enrollment and chart review. Urethral specimens were tested locally for N. gonorrhoeae and C. trachomatis. CDC tested specimens for MG and T. vaginalis. MG resistance mutations were detected by targeted amplification/Sanger sequencing of 23S rRNA loci (macrolide resistance mutations [MRM]) and parC and gyrA (quinolone resistance mutations). Results Among 914 participants with evaluable MG results, MG was detected in 28.7% (95% CI 23.8–33.6). Men with MG were more often black (79.8% vs 66%), Conclusion MG was common among men with urethritis and MRM prevalence high. Persistent symptoms were frequent among men with and without MG. Many participants with macrolide-resistant MG experienced symptom persistence and returned to clinic for evaluation. Disclosure No significant relationships.

Background Numerous studies have shown that Trichomonas vaginalis (TV) infection is related to risk of HIV infection, but fewer studies have compared positivity rates based on HIV status. Further, the majority of studies that have looked at this topic have either been performed outside the US, or in HIV specialized care settings. We performed a secondary analysis of data collected for evaluation of a molecular diagnostic assay for Sexually Transmitted Infections (STI) diagnostics. Methods Study data from patients with evaluable results obtained using a BD MAX CTGCTV study for detection of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and TV were reviewed for HIV status. These women were recruited from 11 sites in the US that included STID clinics; Family Planning clinics, including Planned Parenthood clinics; OB/GYN clinics and other clinic types. No HIV care specialty clinics participated in recruiting patients into this study. CT, GC and TV results based on HIV were compared status using ×2 with α=0.05. Results HIV status data from 2339 women were available. Among HIV negative women the positivity rates for CT, GC, and TV were 6.2%, 1.9%, and 10.3% respectively. Among HIV positive women the positivity rates for CT and TV were 2.1% and 27.1% respectively. No GC coinfection was detected among HIV positive women. For TV, the positivity rate among women with HIV [27.1% (13/48)] was significantly higher than that of among HIV (-) women [10.3% (236/2291)] (p Conclusion While women engaged in HIV specialty care may be tested for STIs routinely, as services are being pushed to more primary care settings, it is important for clinicians to be aware of the importance of STI screening among HIV (+) women, particularly for TV. Disclosure No significant relationships.

Background High rates of repeat T. vaginalis infections post-treatment have been reported. It is essential to understand the origin of these infections (i.e. treatment failure or reinfection) to determine the best secondary prevention measures. Self-reported sexual behavior and medication adherence can be subject to bias. The purpose of this study is to examine the origins of early repeat T. vaginalis infections in women using clinical versus genotype-informed criteria. Methods Women with T. vaginalis confirmed by culture or nucleic acid amplification test (NAAT), who were randomized to receive 2 g or 7-day 500 mg BID metronidazole (MTZ), were retested 3–12 weeks post treatment at test-of-cure (TOC). Viable isolates from women who were TOC TV+ were genotyped (baseline and TOC isolates) and MTZ susceptibility (TOC only) was evaluated. Sexual and treatment adherence histories were elicited by computer-assisted self-administered survey. Treatment failure was defined using two criteria: 1) clinical (a combination of MTZ adherent per self-report+ no follow-up sexual exposure per self-report + no MTZ resistance), and 2) genotype-informed (concordant baseline and TOC genotype with no follow-up sexual exposure per self-report). Results Of 80 repeat positives, 78 were evaluated using clinical and 49 using genotype-informed criteria. Per clinical criteria, 87.2% were treatment failure, 7.7% were reinfection and 5.1% were new infection. Per genotype-informed criteria, 51.0% were treatment failure, 10.2% were reinfection and 38.3% were new infection. In subset analysis, comparing the 49 with both clinical and genotype-informed assessments, 61.2% agreed and 38.8% disagreed (kappa 0.29 indicating poor reliability). Of 44 women who denied having a new partner during follow-up, 14 (31.8%) had a discordant genotype. Conclusion Using either criteria, most TOC T. vaginalis positives were treatment failure rather than re-infections. Clinical and genotype-informed classification were not well correlated. Possible explanations for this will be discussed. Disclosure No significant relationships.

The clinical performance of the Cobas CT/NG assay on the Cobas 6800/8800 systems (Cobas) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae was established in a multisite, prospective collection study using male and female urogenital specimens; supportive data from archived specimens were also included. The results obtained with the Cobas assay were compared with the patient infected status derived from a combination of U.S., The clinical performance of the Cobas CT/NG assay on the Cobas 6800/8800 systems (Cobas) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae was established in a multisite, prospective collection study using male and female urogenital specimens; supportive data from archived specimens were also included. The results obtained with the Cobas assay were compared with the patient infected status derived from a combination of U.S. Food and Drug Administration-approved nucleic acid amplification tests to determine the sensitivity and specificity of detection from each sample type. The sensitivity of Cobas for the detection of C. trachomatis in female specimens was 95.6% (95% confidence interval [CI], 92.4% to 97.4%) for urine; 98.6% (95% CI, 95.2% to 99.6%) and 99.2% (95% CI, 95.4% to 99.9%) for clinician- and self-collected vaginal swab specimens, respectively; 93.3% (95% CI, 89.6% to 95.7%) for endocervical swabs; and 92.5% (95% CI, 88.7% to 95.1%) for cervical swab samples in PreservCyt. The specificity for the detection of C. trachomatis was ≥98.8% for all female sample types. Sensitivity and specificity estimates of Cobas for the detection of C. trachomatis in male urine samples were 100% (96.8% to 100.0%) and 99.7% (95% CI, 99.2% to 99.9%), respectively. The sensitivity of Cobas for the detection of N. gonorrhoeae in female specimens was 94.8% (95% CI, 89.6% to 97.4%) for urine; 100.0% (95% CI, 87.9% to 100.0%) and 100.0% (95% CI, 87.9% to 100.0%) for clinician- and self-collected vaginal swab specimens, respectively; 97.0% (95% CI, 91.5% to 99.0%) for endocervical swabs; and 96.6% (95% CI, 90.6% to 98.8%) for cervical samples in PreservCyt; the specificity for all female sample types was >99.0%. The sensitivity and specificity of Cobas for detecting N. gonorrhoeae in male urine were 100.0% (95% CI, 95.8% to 100.0%) and 99.5% (95% CI, 98.8% to 99.8%), respectively. Fully automated assays help fill the clinical need for a sensitive, high-throughput screening tool to aid public health efforts to control C. trachomatis and N. gonorrhoeae infections.

BACKGROUND –: The optimal timing for nucleic acid amplification testing (NAAT) post-treatment for Trichomonas vaginalis has not been fully established. Testing too soon post-treatment may detect remnant nucleic acid that is not from viable organisms, falsely misclassifying person as infected. The purpose of this study was to examine how long T. vaginalis nucleic acid is detectable post metronidazole (MTZ) treatment. METHODS –: Women diagnosed with T. vaginalis treated with MTZ (2 g single-dose or 500 mg twice daily for 7 days multi-dose) self-collected a vaginal swab for NAAT at baseline and each week post completion of treatment through test of cure (TOC) at week 4, when a culture was also performed. Women who reported interim sexual exposure or who were culture positive at 4 weeks were excluded. Time to first negative NAAT was examined using Kaplan Meier analysis. RESULTS –: All women receiving multi-dose metronidazole were NAAT negative by 21 days and those receiving single-dose by 28 days post completion of treatment. Though over half (60.7%) of the cohort reinitiated sex during follow-up¸ all reported using condoms during sex or that they and their partner were treated prior to sex. Six of 89 (6.7%) had a positive NAAT following their first negative NAAT. CONCLUSIONS –: The optimal timing for T. vaginalis retesting after completion of treatment is three weeks for those receiving multi-dose MTZ and four weeks for those receiving single-dose, though sexual re-exposure and false negatives should be considered.

Background In the United States, less than one-quarter of those who are eligible for pre-exposure prophylaxis (PrEP) have been prescribed the medication. Innovative strategies of PrEP delivery are needed to facilitate access and overcome barriers to care. The objective of this study was to evaluate the referral process from a sexual health center (SHC) to a co-located PrEP clinic as an alternative model of PrEP care. Methods An initial report was generated from the electronic health record (EHR) to determine the number of patients seen at the SHC in 2019. Charts were then manually reviewed to determine whether a PrEP clinic referral was made. For those referred, we determined the method of the referral: PrEP clinic navigator met the patient at the SHC (handoff), the navigator was messaged in the EHR to then schedule the appointment (EHR message), or the patient was provided a card with the navigator’s contact information (card). We also determined whether patients had subsequent visits at the PrEP clinic or SHC. Results From January to December 2019, there were 3570 unique patients seen at the SHC, and 240 (6.7%) were referred to the PrEP clinic. Of 240 referred patients, median age was 29 years; 95 (40%) were non-Hispanic Black and 25 (11%) were Latinx. The majority (n=198, 83%) were male, 32 (13%) were cisfemale, and 9 (4%) were transfemale. An STI was diagnosed on the day of the clinic visit for 116 (49%) patients. Of those who were MSM, 75 (51%) had been diagnosed with an STI in the previous 6 months. In total, 106 referred patients attended an initial PrEP visit and the proportion attending the visit by method of referral was 81%, 38%, and 22% for handoff, EHR message, and card, respectively (p< .0001). Of the 108 patients who attended an initial PrEP visit, 66 (61%) had a subsequent PrEP visit. Of those who did not attend a PrEP visit, 36 (27%) had a subsequent visit at the SHC. Figure 1. Method of Referral from SHC to PrEP Clinic Conclusion Despite co-location of these two clinics, there are significant drop-offs along the PrEP care continuum for this referral system. Navigator-facilitated handoff was the most effective method of referral from SHC to PrEP Clinic, but further efforts are needed to understand barriers to referral. Implementation of rapid PrEP provided at the SHC may be one possible solution to engaging additional patients in PrEP services. Disclosures Meredith E. Clement, MD, FHI360 (Consultant)Gilead (Research Grant or Support)Janssen (Scientific Research Study Investigator)

BACKGROUND Three recent prospective studies have suggested that the 1-g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%-22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to reexamine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. METHODS Men who had sex with women, who received 1-g azithromycin under directly observed therapy for presumptive treatment of nongonococcal urethritis with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine, and TOC screening was performed on urine using nucleic acid amplification tests. Posttreatment vaginal sexual exposure was elicited at TOC. Data from the 3 studies were obtained and reanalyzed. Rates of Ct retest positive were examined for all cases, and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. RESULTS The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). CONCLUSIONS In these samples of men who have sex with women with Ct-related nongonococcal urethritis, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization's target chlamydia treatment failure rate of < 5%.

Key Points Question How does a new point-of-care assay for detection of chlamydia and gonorrhea compare with commercially available laboratory-based molecular diagnostics? Findings This cross-sectional study including 1523 women and 922 men found that a new molecular point-of-care assay was associated with excellent performance compared with laboratory-based molecular diagnostics for vaginal swab samples and has been cleared for use by the US Food and Drug Administration. Male urine samples were associated with good performance in this assay and are undergoing continuing evaluation. Meaning Highly sensitive, rapid chlamydia and gonorrhea testing at the point of care is now a possibility that can support same-day testing and treatment strategies., Importance Rates of chlamydial and gonococcal infection continue to increase in the United States, as do the associated costs of untreated infections. Improved diagnostic technologies that support testing and treating in 1 clinical visit are critical to advancing efforts to control the rates of chlamydial and gonococcal infection. Objective To evaluate the clinical performance of a point-of-care (POC) molecular diagnostic assay for the detection of chlamydia and gonorrhea. Design, Setting, and Participants A noninterventional, cross-sectional clinical study was conducted from September 18, 2018, through March 13, 2019, at sexually transmitted infection (STI), HIV, family planning, and obstetrics and gynecology clinics where STI screening is routine, using a convenience sample and comparing commercially available assays with a new 30-minute POC assay. Patients included were those eligible for STI screening or diagnostic testing who had not taken antibiotics effective against chlamydia or gonorrhea within the previous 28 days. Four vaginal swab samples were collected from women and a first-catch urine sample was obtained from men. Main Outcomes and Measures A composite infection status was used to classify participants as infected if 2 or more comparator results were positive, as not infected if 2 or more comparator samples were negative, and as unevaluable if 1 result was invalid and the other 2 results did not agree with each other. Results Swab samples from 1523 women (median age, 27 years [interquartile range, 17-37 years]), 817 (53.6%) of whom presented with symptoms, and 922 men (median age, 29 years [interquartile range, 17-41 years]), 308 (33.4%) of whom were symptomatic, were tested. For chlamydia, sensitivity of the new POC assay was 96.1% (95% CI, 91.2%-98.3%) for women and 92.5% (95% CI, 86.4%-96.0%) for men. For gonorrhea, sensitivity estimates were 100.0% (95% CI, 92.1%-100.0%) for women and 97.3% (95% CI, 90.7%-99.3%) for men. For chlamydia, specificity of the new POC assay was 99.1% (95% CI, 98.4%-99.5%) for women and 99.3% (95% CI, 98.4%-99.7%) for men. For gonorrhea, specificity estimates were 99.9% (95% CI, 99.5%-100%) for women and 100% (95% CI, 95.5%-100%) for men. Non–laboratory-trained personnel performed 94.8% of all tests (2318 of 2445) during the study. Conclusions and Relevance This study suggests that self-obtained vaginal swab samples were associated with performance equivalent to laboratory-based molecular diagnostics, which can support use of this POC assay in many settings. The availability of an easy-to-use, rapid (30-minute) molecular test for accurate detection of chlamydia and gonorrhea has the power to facilitate testing and treatment in a single patient visit for these STIs., This cross-sectional study evaluates the clinical performance of a point-of-care molecular diagnostic assay for the detection of chlamydia and gonorrhea.

Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.We randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population.From November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal.The majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections. (Funded by the National Institutes of Health and Entasis Therapeutics; ClinicalTrials.gov number, NCT02257918 .).

Among women, trichomoniasis is the most common non-viral sexually transmitted infection worldwide, and is associated with serious reproductive morbidity, poor birth outcomes, and amplified HIV transmission. Single-dose metronidazole is the first-line treatment for trichomoniasis. However, bacterial vaginosis can alter treatment efficacy in HIV-infected women, and single-dose metronidazole treatment might not always clear infection. We compared single-dose metronidazole with a 7-day dose for the treatment of trichomoniasis among HIV-uninfected, non-pregnant women and tested whether efficacy was modified by bacterial vaginosis.In this multicentre, open-label, randomised controlled trial, participants were recruited at three sexual health clinics in the USA. We included women positive for Trichomonas vaginalis infection according to clinical screening. Participants were randomly assigned (1:1) to receive either a single dose of 2 g of metronidazole (single-dose group) or 500 mg of metronidazole twice daily for 7 days (7-day-dose group). The randomisation was done by blocks of four or six for each site. Patients and investigators were aware of treatment assignment. The primary outcome was T vaginalis infection by intention to treat, at test-of-cure 4 weeks after completion of treatment. The analysis of the primary outcome per nucleic acid amplification test or culture was also stratified by bacterial vaginosis status. This trial is registered with ClinicalTrials.gov, number NCT01018095, and with the US Food and Drug Administration, number IND118276, and is closed to accrual.Participants were recruited from Oct 6, 2014, to April 26, 2017. Of the 1028 patients assessed for eligibility, 623 women were randomly assigned to treatment groups (311 women in the single-dose group and 312 women in the 7-day-dose group; intention-to-treat population). Although planned enrolment had been 1664 women, the study was stopped early because of funding limitations. Patients in the 7-day-dose group were less likely to be T vaginalis positive at test-of-cure than those in the single-dose group (34 [11%] of 312 vs 58 [19%] of 311, relative risk 0·55, 95% CI 0·34-0·70; p0·0001). Bacterial vaginosis status had no significant effect on relative risk (p=0·17). Self-reported adherence was 96% in the 7-day-dose group and 99% in the single-dose group. Side-effects were similar by group; the most common side-effect was nausea (124 [23%]), followed by headache (38 [7%]) and vomiting (19 [4%]).The 7-day-dose metronidazole should be the preferred treatment for trichomoniasis among women.National Institutes of Health.

Objectives Infections due to Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are among the most common bacterial sexually transmitted infections worldwide, most of which are asymptomatic. Detection of infection using a variety of specimen types in symptomatic and asymptomatic subjects is important to effectively combat CT/NG infections. The performance of the cobas CT/NG v2.0 test was assessed for urogenital swabs, urine and cervical cytology samples collected in PreservCyt Solution from 5266 symptomatic and asymptomatic women (including 202 who were pregnant), and urine from 738 men. Methods Sensitivity and specificity were estimated compared with a patient infected status determined using two US Food and Drug Administration–cleared nucleic acid amplification tests. Results Among 6004 participants, 487 CT (8.1%) and 159 NG (2.6%) infections were identified. Sensitivity estimates for CT for women ranged from 91.2% to 97.6% depending on specimen type, and the estimate for male urine specimens was 98.4%. Specificity for CT ranged from 99.2% to 99.7%. Sensitivity estimates for NG ranged from 95.6% to 100.0% for women, and the estimate for men was 100.0%. Specificity for NG ranged from 99.3% to 100.0%. Conclusions The cobas CT/NG v2.0 test performs well using urogenital swabs, urine and cervical samples collected in PreservCyt solution.

Trichomoniasis is the most prevalent curable sexually transmitted disease (STD). It has been associated with preterm birth and the acquisition and transmission of HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA cleared in the United States for detection of Trichomonas vaginalis in specimens from both women and men. This study reports the results of a multicenter study recently conducted using the Xpert TV ( T. vaginalis ) assay to test specimens from both men and women. On-demand results were available in as little as 40 min for positive specimens. A total of 1,867 women and 4,791 men were eligible for inclusion in the analysis. In women, the performance of the Xpert TV assay was compared to the patient infected status (PIS) derived from the results of InPouch TV broth culture and Aptima NAAT for T. vaginalis . The diagnostic sensitivities and specificities of the Xpert TV assay for the combined female specimens (urine samples, self-collected vaginal swabs, and endocervical swabs) ranged from 99.5 to 100% and 99.4 to 99.9%, respectively. For male urine samples, the diagnostic sensitivity and specificity were 97.2% and 99.9%, respectively, compared to PIS results derived from the results of broth culture for T. vaginalis and bidirectional gene sequencing of amplicons. Excellent performance characteristics were seen using both female and male specimens. The ease of using the Xpert TV assay should result in opportunities for enhanced screening for T. vaginalis in both men and women and, hopefully, improved control of this infection.

Introduction A recent meta-analysis demonstrated superiority of multi-dose metronidazole (MTZ) over the CDC and WHO recommended 2 g dose for the treatment of T. vaginalis (TV). Another study among HIV+ women with TV found higher test-of-cure (TOC)+ rates among women who had asymptomatic bacterial vaginosis (BV) than those without BV. The purpose of this study was to measure the TOC TV+ rate and to examine if the presence of BV influenced that rate. Methods HIV-/TV+ women treated with 2 g oral directly observed MTZ and who completed their TOC visit 3–12 weeks post treatment were included. Women were tested for TV using NAAT and surveyed via computer at baseline and TOC. Nugent scores≥7, calculated from vaginal gram stain, were considered BV+. MTZ susceptibility testing was performed on TOC TV+ specimens. Results Of 227 TV+ women included baseline the mean age was 31.3 (S.D. 9.9), 95.2% were African American, 39.3% had multiple male partners in the prior 3 months, 32.3% regularly smoked, 19.4% were binge drinkers, 48.9% had BV and 5.4% had yeast on the gram stain. At TOC, 19.8% were NAAT TV+. Of the 45 TOC-TV+ women, 44 provided sexual exposure information and 10/44 (24.4%) reported sexual re-exposure to baseline partner or sexual exposure to a new partner. Two of 26 (7.7%) TOC+ specimens that underwent susceptibility testing had low to moderate MTZ resistance (50–100 ug/ml). There were no differences in TOC NAAT+ rates by BV, sexual re-exposure to a baseline partner, sexual exposure to a new partner, regular smoking, binge drinking, or by the presence of yeast (p>0.22). Conclusion TOC NAAT+ rate after 2 g MTZ dose was high (19.8%) and isolates from these women were susceptible to MTZ (94.3%). Most TOC+ women (75.6%) reported no sexual exposure/re-exposure during follow-up suggesting that most cases were treatment failures. Selected behavioural factors and BV did not did not appear to influence TV treatment. The 2 g MTZ dose for TV recommended by CDC and WHO, should be reevaluated in light of more sensitive NAAT.

Introduction Both Trichomonas vaginalis (TV) and bacterial vaginosis (BV) cause vaginitis and place women at higher risk for HIV infection. Both are treated with metronidazole (Mtz) but at different doses. The purpose of this study was to examine the co-occurrence of these infections and BV treatment outcomes among TV+/BV+ women multi-dose Mtz for the treatment of TV. Methods Women attending three sexually transmitted disease clinics in the southern US who had a diagnosis of TV (culture or NAAT confirmed) were interviewed and examined for BV using a Nugent score ≥7. Women were randomised to either 2 g single dose or 500 mg Mtz BID for 7 days multi-dose for the treatment of TV and followed 3–12 weeks post TV treatment and retested for both TV and BV. Medical records were abstracted for Amsel criteria for a subset of the cohort. Results Of 528 TV+ women at baseline, 49.8% also had BV per Nugent score, 44.3% reported a history of BV and 5.9% also had yeast. Of 289 women whose medical records were abstracted, 23.5% had a vaginal discharge consistent with BV (i.e. thin and white/grey), and 34.1% were BV+ per Amsel at baseline. Of the 46 women who were BV+ at baseline per Amsel (i.e. diagnosed at point of care) and per Nugent (i.e. lab diagnosed) and were treated with multi-dose Mtz, 96% reported taking all their medicine. While 36% of these women reported condomless sex during follow-up, there was no association between sexual exposure and BV status at TOC. Of these 46 women, 42.9% remained BV+ at TOC and 19.4% reported BV-related symptoms. BV status at TOC was not associated with TV cure rates (p>0.56). Conclusion A high rate of BV co-infection (49.8%) was found among women with TV, much of which was asymptomatic. The rate of BV persistence post multi-dose Mtz was also high both microbiologically (42.9%) and clinically (19.4%) and did not appear to be influenced by TV treatment status. Additional research and development of novel therapeutics (i.e. biofilm disruptors) are urgently needed for women with BV, particularly among TV+ women where BV rates are high.

We evaluated the BD Viper LT System for detection of Chlamydia trachomatis and Neisseria gonorrhoeae using samples collected from symptomatic patients that included urine, vaginal swabs, and cervical samples in liquid-based cytology media. Results were compared with those obtained using the BD Viper XTR platform. The positive and negative percent agreements for all sample types were at least 95.8% and at least 96.4% for chlamydia and gonorrhea and at least 95.0% when both organisms were present, respectively. This medium throughput system performs well compared with a high-throughput platform and may offer smaller health care facilities the opportunity to test for these infections locally.