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Neisseria meningitidis causes invasive meningococcal diseases and has also been identified as a causative agent of sexually transmitted infections, including urethritis. Unencapsulated sequence type 11 meningococci containing the gonococcal aniA-norB locus and belonging to the United States N. meningitidis urethritis clade (US_NmUC) are causative agents of urethral infections in the United States, predominantly among men who have sex with men. We identified 2 subtypes of unencapsulated sequence type 11 meningococci in Japan that were phylogenetically close to US_NmUC, designated as the Japan N. meningitidis urethritis clade (J_NmUC). The subtypes were characterized by PCR, serologic testing, and whole-genome sequencing. Our study suggests that an ancestor of US_NmUC and J_NmUS urethritis-associated meningococci is disseminated worldwide. Global monitoring of urethritis-associated N. meningitidis isolates should be performed to further characterize microbiologic and epidemiologic characteristics of urethritis clade meningococci.

Background: Extragenital gonorrhea (GC) and chlamydia (CT) are usually asymptomatic and only detected through screening. Ceftriaxone plus azithromycin is the recommended GC treatment; monotherapy (azithromycin or doxycycline) is recommended for CT. In urethral CT-positive/urethral GC-negative persons who are not screened extragenitally, CT monotherapy can lead to GC undertreatment and may foster the development of gonococcal antimicrobial resistance. We assessed urethral and extragenital GC and CT positivity among men who have sex with men (MSM) attending sexually transmitted disease clinics., Methods: We included visit data for MSM tested for GC and CT at 30 sexually transmitted disease clinics in 10 jurisdictions during January 1, 2015, and June 30, 2019. Using an inverse-variance random effects model to account for heterogeneity between jurisdictions, we calculated weighted test visit positivity estimates and 95% confidence intervals (CI) for GC and CT at urethral and extragenital sites, and extragenital GC among urethral CT-positive/GC-negative test visits., Results: Of 139,718 GC and CT test visits, we calculated overall positivity (GC, 16.7% [95% CI, 14.4-19.1]; CT, 13.3% [95% CI, 12.7-13.9]); urethral positivity (GC, 7.5% [95% CI, 5.7-9.3]; CT, 5.2% [95% CI, 4.6-5.8]); rectal positivity (GC, 11.8% [95% CI, 10.4-13.2]; CT, 12.6% [95% CI, 11.8-13.4]); and pharyngeal positivity (GC, 9.1% [95% CI, 7.9-10.3]; CT, 1.8% [95% CI, 1.6-2.0]). Of 4566 urethral CT-positive/GC-negative test visits with extragenital testing, extragenital GC positivity was 12.5% (95% CI, 10.9-14.1)., Conclusions: Extragenital GC and CT were common among MSM. Without extragenital screening of MSM with urethral CT, extragenital GC would have been undetected and undertreated in approximately 13% of these men. Undertreatment could potentially select for antimicrobial resistance. These findings underscore the importance of extragenital screening in MSM.

Urethritis, or inflammation of the urethra, is one of the most common reasons men seek clinical care. Sexually transmitted pathogens including Neisseria gonorrhoeae are responsible for over half of the symptomatic urethritis cases in U.S. men. Recently, clinics in Indianapolis, Columbus, Atlanta, and other U.S. cities began to note increasing numbers of men presenting with urethritis and Gram-negative intracellular diplococci in their urethral smears who test negative for N. gonorrhoeae. Many of these discordant cases, which have periodically reached highs of more than 25% of presumed gonococcal cases in some sexually transmitted infection clinics in the U.S. Midwest, are infected with strains in a novel urethrotropic clade of Neisseria meningitidis ST-11 (US_NmUC). However, no cultivation-independent tests are available for the US_NmUC strains, and prior studies relied on microbial culture and genome sequencing to identify them. Here, we describe a PCR test that can identify the US_NmUC strains and distinguish them from commensal and invasive N. meningitidis strains as well as N. gonorrhoeae. Our SimpleProbe®-based real-time PCR assay targets a conserved nucleotide substitution in a horizontally acquired region of US_NmUC strain genomes. We applied the assay to 241 urine specimens whose microbial compositions had previously been determined by deep shotgun metagenomic sequencing. The assay detected the single US_NmUC positive case in this cohort, with no false positives. Overall, our simple and readily adaptable assay could facilitate investigation of the pathogenesis and epidemiology of the US_NmUC clade., Competing Interests: The authors have declared that no competing interests exist.

Clusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non-encapsulated meningococcal clade (the US Nm urethritis clade, US_NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US_NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64-256 µg ml -1 ). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384-1024 µg ml -1 ) and colistin (MIC 256 µg ml -1 ) as well as enhanced LL-37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US_NmUC isolates was due to active Mtr efflux and LptA-mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high-level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross-resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High-level resistance to AMPs may contribute to the pathogenesis of US_NmUC., (© 2018 John Wiley & Sons Ltd.)

Antimicrobial resistance in Neisseria gonorrhoeae has severely limited the number of treatment options, and the emergence of extended-spectrum cephalosporin resistance threatens the effectiveness of the last remaining recommended treatment regimen. This study assessed the in vitro susceptibility of N. gonorrhoeae to ETX0914, a novel spiropyrimidinetrione that inhibits DNA biosynthesis. In vitro activity was determined by agar dilution against 100 N. gonorrhoeae isolates collected from men presenting with urethritis in the USA during 2012-2013 through the Gonococcal Isolate Surveillance Project. The minimum inhibitory concentration (MIC) that inhibited growth in 50% (MIC50) and 90% (MIC90) of isolates was calculated for each antimicrobial agent. ETX0914 demonstrated a high level of antimicrobial activity against N. gonorrhoeae, including isolates with decreased susceptibility or resistance to currently available agents. The ability of ETX0914 to inhibit the growth of N. gonorrhoeae was similar to ceftriaxone, which is currently recommended in combination with azithromycin to treat gonorrhoea. The data presented in this study strongly suggest that ETX0914 should be evaluated in a clinical trial for the treatment of N. gonorrhoeae., (Published by Elsevier B.V.)

Background: Sexually transmitted infections (STIs) of the pharynx are common among men who have sex with men (MSM); the degree to which these infections are transmitted through oral sex is unknown., Methods: We conducted a case-control study of MSM attending Public Health-Seattle & King County STD Clinic between 2001 and 2013 to estimate the proportion of symptomatic urethritis cases attributable to oral sex using two methods. First, we categorised men into the following mutually exclusive behavioural categories based on their self-reported sexual history in the previous 60 days: (1) only received oral sex (IOS); (2) 100% condom usage with insertive anal sex plus oral sex (PIAI); (3) inconsistent condom usage with anal sex (UIAI); and (4) no sex. We then determined the proportion of cases in which men reported the oropharynx as their only urethral exposure (IOS and PIAI). Second, we calculated the population attributable risk per cent (PAR%) associated with oral sex using Mantel-Haenszel OR estimates., Results: Based on our behavioural categorisation method, men reported the oropharynx as their only urethral exposure in the past 60 days in 27.5% of gonococcal urethritis, 31.4% of chlamydial urethritis and 35.9% non-gonococcal, non-chlamydial urethritis (NGNCU) cases. The PAR%s for symptomatic gonococcal urethritis, chlamydial urethritis and NGNCU attributed to oropharyngeal exposure were 33.8%, 2.7% and 27.1%, respectively., Conclusions: The pharynx is an important source of gonococcal transmission, and may be important in the transmission of chlamydia and other, unidentified pathogens that cause urethritis. Efforts to increase pharyngeal gonorrhoea screening among MSM could diminish STI transmission., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific subpopulations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

In April 2013, the Centers for Disease Control and Prevention (CDC) convened an advisory group to assist in development of the 2015 CDC sexually transmitted diseases (STDs) treatment guidelines. The advisory group examined recent abstracts and published literature addressing the diagnosis and management of sexually transmitted infections. This article summarizes the key questions, evidence, and recommendations for the diagnosis and management of epididymitis that were considered in preparation of the 2015 CDC STD treatment guidelines., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We aimed to create a system for predicting which male emergency department (ED) patients with suspected chlamydial and/or gonococcal urethritis would have laboratory-confirmed infections based on clinical factors available at the initial ED encounter., Methods: We used statistical models to develop a system to predict either the presence or absence of laboratory-confirmed chlamydial and/or gonorrheal urethritis based on patient demographics and presenting symptoms. Data for the system were extracted from a retrospective chart review of adult male patients who were suspected of having, and were tested for, chlamydial and/or gonococcal urethritis at an adult, urban, northeastern United States, academic ED from January 1998 to December 2004., Results: Among the 822 patients tested, 29.2% had chlamydia, gonorrhea, or both infections; 13.8% were infected with chlamydia alone, 12.1% were infected with gonorrhea alone, and 3.3% were infected with both. From the statistical models, the following factors were predictive of a positive laboratory test for chlamydia and/or gonorrhea: age < or = 24 years, penile discharge, sexual contact with someone known to have chlamydia and/or gonorrhea, and not having health care insurance. A system using a hierarchical grouping of these factors based on the predicted probabilities of a laboratory-confirmed chlamydial and/or gonococcal urethritis, paired with baseline ED prevalence of these infections, was confirmed through internal validation testing to modestly predict which patients had or did not have a laboratory-confirmed infection., Conclusions: This system of a combination of risk factors available during the clinical encounter in the ED modestly predicts which adult male patients suspected of having chlamydial and/or gonorrheal urethritis are more likely to have or not have a laboratory-confirmed infection. A prospective study is needed to create and validate a clinical prediction rule based on the results of this system.

Gonorrhea (GU) and nongonococcal urethritis (NGU), the commonest sexually transmitted diseases in men, are endemic at high levels in most regions of the world, despite effective methods of diagnosis and treatment. NGU is a milder disease with a longer incubation period and longer duration of symptoms before treatment. Although Chlamydia trachomatis and Ureaplasma urealyticum appear to account for a majority of NGU cases, the cause of approximately 20% of cases remains unknown. NGU is about twice as common as GU in Western countries, and on the basis of national statistics from Great Britain, its incidence has been thought to be increasing more rapidly. However, data from individual clinics suggest that incidence of both diseases has remained stable over the past decade. The increased incidence of NGU in Great Britain over the past decade probably results from increased recognition or reporting. Marked socioeconomic and racial differences in both relative incidence of and susceptibility to NGU and GU have been found repeatedly but are unexplained. Men appear to transmit GU to women more efficiently than vice versa. Neisseria gonorrhoeae appears to be more infectious than C. trachomatis for both men and women, but interpretation of differences in susceptibility and transmission is hindered by ignorance of natural and acquired immunity to these agents. Of the several important time intervals in chains of transmission of venereal urethritis, only incubation periods and iatrotropic intervals for GU and NGU and the posttreatment period of infectivity for GU are known.

The therapeutic efficiency of kanamycin and vibromycin in treatment of gonorrhea was studied on 112 and 86 males respectively. Clinical and etiological recovery was observed in 85.6 and 92.9 per cent of the patients. The best therapeutic results were obtained with the use of vibromycin in a course dose of 500 mg. A single administration of the drug in a course dose of 300 mg was less effective. The gonococci disappeared from the urethra secretion under the effects of kanamycin and vibromycin 4-10 hours after beginning of the treatment. The minimum concentration of vibromycin inhibiting the gonococcal growth on nutrient media ranged from 0.02 to 0.4 units/ml.

We studied patients with non-specific urethritis and control subjects at our dispensary. These patients and controls were matched for age, rank and sexual activity, and studied for the presence of bacteria, virus, Trichomonas and Mycoplasma. No significant bacteria were found in either group. No Trichomonas was identified, only 1 herpes II was recovered and no cytomegalovirus was found. Mycoplasma were cultured from patients and controls. The rate of colonization varied, depending upon several factors, but the significant factors seemed to be associated with the number of sexual partners. Those men with more than 1 sexual partner had a significantly increased colonization with Mycoplasma.