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Background: The etiology of nongonococcal urethritis (NGU) is incompletely understood. We sought to determine if genitourinary bacterial diversity or specific taxa were associated with incident NGU., Methods: From August 2014-July 2018, men who have sex with women attending a sexual health clinic were clinically evaluated, including Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) testing, at enrollment and six monthly visits. New cases of NGU (≥5 PMNs/HPF in urethral exudates plus either symptoms or visible discharge) and their visit preceding NGU diagnosis were matched 1:1 to two sequential visits without NGU (controls). We determined associations with incident NGU and applied broad-range 16S rRNA gene polymerase chain reaction and sequencing to urine samples from each visit. We used conditional logistic regression to evaluate the association of Shannon Diversity Index (SDI), species richness, Haemophilus influenzae, Fannyhessea vaginae, Lactobacillus iners, and Streptococcus mitis group with incident non-CT-non-MG-NGU (NCNM-NGU)., Results: Of 62 matched case-control pairs, median age was 32. Higher SDI the previous month was associated with higher odds of incident NCNM-NGU (adjusted odds ratio [aOR] = 2.8 per unit increase; 95% CI = 1.03-7.47), as was F. vaginae at NGU diagnosis (aOR = 5.1; 95% CI = 1.28-20.15), F. vaginae acquisition (aOR = 13.8; 95% CI = 1.96-97.33) and consistent carriage of F. vaginae (aOR = 16.1; 95% CI = 1.66-156.29). Odds of NCNM-NGU were higher when L. iners cleared between visits (aOR = 18.0; 95% CI = 1.08-299.24). Neither H. influenzae nor S. mitis group were associated with incident NCNM-NGU., Conclusions: F. vaginae acquisition/detection and L. iners clearance were associated with urethritis. This merits investigation in larger longitudinal studies using species-specific detection methods., Competing Interests: Conflicts of Interest: LEM has received consulting fees from Health Advances, speaker’s fees from MedConnect, research funding and materials from Hologic, Inc. and Nabriva Therapeutics, and travel support from Hologic, Inc. DNF and TLF receive a royalty from BD for intellectual property around molecular diagnosis of bacterial vaginosis. CMK has received research supplies from Hologic, Inc. and research support from Gilead Sciences., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Sexual behavior may influence the composition of the male urethral microbiota, but this hypothesis has not been tested in longitudinal studies of men who have sex with men (MSM)., Methods: From December 2014 to July 2018, we enrolled MSM with nongonococcal urethritis (NGU) attending a sexual health clinic. Men attended 5 in-clinic visits at 3-week intervals, collected weekly urine specimens at home, and reported daily antibiotics and sexual activity on weekly diaries. We applied broad-range 16S rRNA gene sequencing to urine. We used generalized estimating equations to estimate the association between urethral sexual exposures in the prior 7 days (insertive oral sex [IOS] only, condomless insertive anal intercourse [CIAI] only, IOS with CIAI [IOS + CIAI], or none) and Shannon index, number of species (observed, oral indicator, and rectal indicator), and specific taxa, adjusting for recent antibiotics, age, race/ethnicity, HIV, and preexposure prophylaxis., Results: Ninety-six of 108 MSM with NGU attended ≥1 follow-up visit. They contributed 1140 person-weeks of behavioral data and 1006 urine specimens. Compared with those with no urethral sexual exposures, those with IOS only had higher Shannon index ( P = 0.03 ) but similar number of species and presence of specific taxa considered, adjusting for confounders; the exception was an association with Haemophilus parainfluenzae . CIAI only was not associated with measured aspects of the urethral microbiota. IOS + CIAI was only associated with presence of H. parainfluenzae and Haemophilus ., Conclusions: Among MSM after NGU, IOS and CIAI did not seem to have a substantial influence on measured aspects of the composition of the urethral microbiota., Competing Interests: Conflict of Interest of Sources of Funding: This work was supported by the National Institutes of Health (grant number U19 AI113173). L.C.C. was supported by the National Institutes of Health (grant number TL1 TR002318 trainee support). K.A.T. was supported by the University of Washington/Fred Hutch Center for AIDS Research, a program funded by the National Institutes of Health (grant number P30 AI027757). Study data were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at the University of Washington Institute of Translational Health Sciences and supported by the National Institutes of Health (grant number UL1 TR002319). C.M.K. has received donations of test kits and reagents from Hologic, Inc. M.R.G. has conducted studies unrelated to this work supported by grants from Hologic, Inc. L.E.M. has received research support and honoraria from Hologic, Inc., and Nabriva Therapeutics. All other authors declare that they have no conflict of interest., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Incidence and risk factors for nongonococcal urethritis (NGU) remain poorly defined. We conducted a cohort study to estimate the incidence of NGU and identify risk factors in men who have sex with women., Methods: We enrolled cisgender male sexually transmitted disease clinic attendees 16 years or older who reported exclusively female partners. At enrollment and 6 monthly follow-up visits, men underwent a clinical examination, provided urethral swab and urine specimens, completed a sexual behavior survey and biweekly diaries, and were tested for Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) using Aptima assays (Hologic, Inc). Nongonococcal urethritis was defined as ≥5 polymorphonuclear leukocytes per high-power field plus either urethral symptoms or visible discharge. We estimated the incidence of NGU overall, asymptomatic and symptomatic NGU, non-CT/non-MG NGU, and CT/MG-associated NGU using Poisson regression for clustered outcomes. We performed relative risk binomial regression for clustered data to identify characteristics associated with incident NGU., Results: From August 2014 to July 2018, 307 participants at risk for NGU contributed 109.4 person-years. Median age was 32 years, and 52% were White. At enrollment, 107 men had NGU; of these, 88% were symptomatic, 27% had CT, and 22% had MG. Fifty men had 60 cases of incident NGU (incidence rate, 56 per 100 person-years; 95% confidence interval, 43-74). Unlike prevalent NGU at enrollment, CT/MG-associated incident NGU was rare (incidence rate, 7; 95% confidence interval [CI], 4-15), and most (78%) incident NGU was asymptomatic. Risk factors for incident NGU were ≤ high school education (adjusted rate ratio [ARR], 2.45; 95% CI, 1.19-5.00), history of CT (ARR, 2.15; 95% CI, 1.08-4.27), history of NGU (ARR, 2.67; 95% CI, 1.27-5.62), and NGU at enrollment (ARR, 2.03; 95% CI, 1.04-3.98). Neither condom use nor having a new partner was associated with incident NGU; Black race was only associated with incident symptomatic and non-CT/non-MG NGU., Conclusions: Incidence of NGU was high, predominantly non-CT/non-MG and asymptomatic. Future studies should investigate the etiology and clinical significance of asymptomatic NGU., Competing Interests: Conflict of Interest and Sources of Funding: L.E.M. has received honoraria, reagents, and test kits for diagnostic assays from Hologic, Inc. L.C.C. and E.R. have received trainee support from the Institute of Translational Health Sciences (grant number TL1 TR002318). M.R.G. has received grants from the National Institutes of Health, Hologic, and GSK. All other authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the article have been disclosed., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

From February 2015 to October 2017, among 20 men who have sex with men with Mycoplasma genitalium-associated nongonococcal urethritis, 15% had macrolide resistance and S83I ParC mutations. Azithromycin followed by moxifloxacin cleared Mycoplasma genitalium in 2 of 2 with and 11 of 13 without S83I mutations. Dual failures were cleared after doxycycline. S83I mutations were not associated with moxifloxacin failure.

Background: Standard counseling at nongonococcal urethritis (NGU) diagnosis includes advice to abstain from sex for at least 7 days and until symptoms resolve., Methods: From December 2014 to July 2018, we enrolled men who have sex with men and received azithromycin (1 g) for NGU at the Public Health-Seattle and King County STD Clinic. Over 12 weeks of follow-up, participants reported daily urethral symptoms and sexual activity on web-based diaries. Nongonococcal urethritis was defined as urethral symptoms or visible urethral discharge plus 5 or greater polymorphonuclear leukocytes per high-power field. Time of symptom resolution was defined as the first of 5 consecutive asymptomatic days., Results: Of 100 participants with NGU and no Chlamydia trachomatis (CT)/Mycoplasma genitalium (MG) coinfection, 36 (36%), 22 (22%), and 42 (42%) had CT-NGU, MG-NGU, and non-CT/non-MG NGU, respectively. Among men with MG-NGU, 94% had a macrolide resistance mutation. For all etiologies, median time to symptom resolution after azithromycin was 7 days (95% confidence interval [CI], 5-9); 37% had symptoms lasting longer than 7 days. For men with CT-NGU, MG-NGU, and non-CT/non-MG NGU, median time to symptom resolution was 4 days (95% CI, 2-6; 16% >7 days), undefined days (95% CI, 7 to undefined; 60% >7 days), and 7 days (95% CI, 5-11; 46% >7 days), respectively. Median time to first sexual activity (any type) was 12 days (95% CI, 11-17); it was 16 days (95% CI, 12-18) to first urethral sexual exposure. Twenty-seven percent did not avoid urethral exposure for the recommended period., Conclusions: Counseling at NGU diagnosis should educate patients that symptoms may persist more than 7 days, particularly for non-CT NGU, and emphasize the rationale for the 7-day abstinence period.

Background: The ideal approach to triaging sexually transmitted disease (STD) clinic patients between testing-only express visits and standard visits with clinician evaluation is uncertain., Methods: In this cross-sectional study, we used classification and regression tree analysis to develop and validate the optimal algorithm for predicting which patients need a standard visit with clinician assessment (i.e., to maximize correct triage). Using electronic medical record data, we defined patients as needing a standard visit if they reported STD symptoms, received any empiric treatment, or were diagnosed as having an infection or syndrome at the same visit. We considered 11 potential predictors for requiring medical evaluation collected via computer-assisted self-interview when constructing the optimized algorithm. We compared test characteristics of the optimized algorithm, the Public Health-Seattle and King County STD Clinic's current 13-component algorithm, and a simple 2-component algorithm including only presence of symptoms and contact to STD., Results: From October 2010 to June 2015, 18,653 unique patients completed a computer-assisted self-interview. In the validation samples, the optimized, current, and simple algorithms appropriately triaged 90%, 85%, and 89% of patients, respectively. The optimized algorithm had lower sensitivity for identifying patients needing standard visits (men, 94%; women, 93%) compared with the current algorithm (men, 95%; women, 98%), as did the simple algorithm (men, 91%; women, 93%). The optimized, current, and simple algorithms triaged 31%, 23%, and 33% of patients to express visits, respectively., Conclusions: The overall performance of the statistically optimized algorithm did not differ meaningfully from a simple 2-component algorithm. In contrast, the current algorithm had the highest sensitivity but lowest overall performance.

Background: Many sexually transmitted disease (STD) clinics offer testing-only "express" visits. We evaluated the express care triage algorithm that is based on a computer-assisted self-interview (CASI) used in the Public Health-Seattle and King County STD Clinic., Methods: During the analysis period, patients received a clinician evaluation irrespective of triage status. In this cross-sectional study, we compared the algorithm triage status to a disease-focused outcome determined by medical record review. We defined a patient as "needing a standard visit" if they reported key symptoms, received empiric treatment, or were diagnosed with an infection or syndrome at the same visit. We estimated the sensitivity of the algorithm for identifying patients who needed a standard visit and identified the characteristics of patients who could have received express care but were excluded from it by the algorithm., Results: Between October 2010 and June 2015, patients completed a CASI at 32,113 visits; 23% were triaged by the algorithm to express care. The triage status was appropriate for 21,337 (87%) men and 6259 (82%) women. The algorithm had 95% and 98% sensitivity for identifying men and women, respectively, needing standard visits. The most common reason for mistriage to express care was patient report of symptoms to clinicians that they did not disclose to the CASI. Of women who could have received express care, only 33% were triaged to it by the algorithm; the remainder was triaged to standard visits, primarily for health service indications., Conclusions: The CASI-based algorithm accurately identified patients who were eligible for express care based on a disease-focused outcome.