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Background: Mycoplasma genitalium is a major contributor to persistent/recurrent urethritis cases. However, there are limited published studies on recent trends of persistent/recurrent urethritis., Methods: A retrospective analysis was conducted of men presenting with symptomatic urethritis in 16 sexually transmitted disease (STD) clinics from 2015 to 2019. Poisson regression was used to assess trends in the annual proportions of urethritis episodes with follow-up (FU) characterized with persistent/recurrent urethritis symptoms. Results were also stratified by results of chlamydia (CT) and gonorrhea (NG) testing and treatment prescribed., Results: There were 99,897 urethritis episodes, from 67,546 unique men. The proportion of episodes with persistent/recurrent symptomatic FU visits increased 50.8% over a 4-year period (annual percentage change [APC], 11.3%; 95% confidence interval [CI], 6.5-16.3). Similar trends were observed in nonchlamydial nongonococcal urethritis episodes (APC, 12.7%; 95% CI, 6.8-18.9) but increases among those positive for NG (APC, 12.1%; 95% CI, -2.3 to -28.5) or for CT (APC, 7.3%; 95% CI, -6.7 to 23.5) were not statistically significant. Among episodes who received azithromycin as first-line treatment, increases in the proportion of persistent/recurrent FU visits were observed (APC, 12.6%; 95% CI, 8.6-16.7). For episodes where first-line treatment was doxycycline, no significant increases were detected (APC, 4.3%; 95% CI, -0.3 to 9.2)., Conclusions: We found an increase in the proportion of urethritis episodes with persistent or recurrent symptoms over time. Given these observed trends in episodes negative for NG or CT, an etiology not detectable by routine diagnostics was a likely factor in increased persistence, suggesting patients with urethritis may benefit from diagnostic testing for M. genitalium during an initial symptomatic presentation., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

The occurrence of cysts and papulopustules along the midline penile raphe, as a complication of gonococcal urethritis, is considered an exceptional presentation. These lesions are related to developmental abnormalities in the fusion of the lower portion of the ventral abdominal wall during embryogenesis, which create small pathways along the raphe of the penis, prone to secondary infection in the presence of gonococcal urethritis. We present the case of a 25-year-old male who experienced these lesions twice, coinciding with two separate episodes of gonococcal urethritis following unprotected sex. Treatment with intramuscular ceftriaxone resolved both the urethritis and cystic lesions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pharyngeal infection is more difficult to diagnose and treat than genital or rectal infection and can act as a reservoir for gonococcal infection. We determined the prevalence of pharyngeal gonorrhea in Korean men with urethritis and analyzed the molecular characteristics and antimicrobial susceptibility of the isolates., Methods: Seventy-two male patients with symptoms of urethritis who visited a urology clinic in Wonju, Korea, between September 2016 and March 2018 were included. Urethral and pharyngeal gonococcal cultures, antimicrobial susceptibility testing, Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST), and multiplex real-time PCR (mRT-PCR) were performed., Results: Among the 72 patients, 59 tested positive for gonococcus by mRT-PCR. Of these 59 patients, 18 (30.5%) tested positive in both the pharynx and urethra, whereas 41 tested positive only in the urethra. NG-MAST was feasible in 16 out of 18 patients and revealed that 14 patients had the same sequence types in both urethral and pharyngeal specimens, whereas two patients exhibited different sequence types between the urethra and pharynx. Of the 72 patients, 33 tested culture-positive. All patients tested positive only in urethral specimens, except for one patient who tested positive in both. All culture-positive specimens also tested positive by mRT-PCR. All isolates were susceptible to azithromycin and spectinomycin, but resistance rates to ceftriaxone and cefixime were 2.9% and 14.7%, respectively., Conclusions: The prevalence of pharyngeal gonorrhea in Korean men with gonococcal urethritis is as high as 30.5%, highlighting the need for pharyngeal screening in high-risk groups. Ceftriaxone is the recommended treatment for pharyngeal gonorrhea.

BACKGROUND Urogenital bacterial infections have a high incidence in humans. The most frequent cause of infections of the urogenital tract is gram-negative bacteria. Antibiotics are very effective in curing infectious diseases but they are accompanied by health complications. Probiotics are live microorganisms that are believed to confer a beneficial effect on human health when consumed in adequate amounts. This study aimed to compare outcomes from antibiotic treatment with and without the use of probiotics in 897 patients with lower urogenital tract infections, including cystitis, urethritis, prostatitis, and vulvovaginitis. MATERIAL AND METHODS A total of 897 patients aged 18 to 55 years were included in this research. Patients were divided into an intervention group including 460 patients (254 women, 206 men) and a comparison group including 437 patients (240 women, 197 men). The probiotics received by patients were capsules of ProBalans®. The diagnosis of cystitis, urethritis, prostatitis, vulvovaginitis, and sexually transmitted infection was done using several tests, and antibiotics were used for treatment. Qualitative data were analyzed using the chi-square or Fisher exact test. RESULTS We found a significant difference regarding patients' impressions of improvement after therapy between patients in the intervention group and the comparison group. CONCLUSIONS Use of probiotics together with antibiotics in the treatment of urogenital tract infection can help to reduce the adverse effects of antibiotics, increase the efficiency of antibiotic therapy, and reduce bacterial resistance to antibiotics. However, further research is needed to confirm these potential health benefits.

Schaalia turicensis is facultative anaerobic Gram-positive bacillus that commonly inhabits the oropharynx, gastrointestinal, and genitourinary tract of healthy individuals. This organism has been co-isolated with Neisseria gonorrhoeae from 15-year-old Thai male patient with gonococcal urethritis in Bangkok, Thailand. In this study, we characterized the class 1 integron in S. turicensis isolate using whole-genome sequencing and bioinformatics analysis. Sequencing analysis confirmed the presence of an imperfect class 1 integron located on chromosome and a novel 24.5-kb-long composite transposon, named Tn7083. The transposon Tn7083 carried genes encoding chloramphenicol resistance (cmx), sulfonamide resistance (sul1), and aminoglycoside resistance [aph(6)-Id (strB), aph(3'')-Ib (strA), aph(3')-Ia]., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Mycoplasma genitalium (MG) is a common cause of non-gonococcal urethritis, but a role in acute or chronic prostatitis has not been described. We describe the case of a 42-year-old man with recurrent urinary tract infections since 2018 who developed chronic prostatitis despite several and prolonged antibiotic courses. Multiparametric prostatic magnetic resonance showed peripheral inflammatory alterations. A 4-glass Meares-Stamey test detected MG in the third voided bladder (VB3) sample. Moxifloxacin 400 mg daily for 28 days resulted in sustained clinical and microbiological cure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from MSD K.K., Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Hiroyuki Nishiyama received research funding from Chugai Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Junichi Inokuchi received research funding from Chugai Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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.

Neisseria meningitidis (Nm ) is a bacterial pathogen responsible for invasive meningococcal disease. Though typically colonizing the nasopharynx, multiple outbreaks of meningococcal urethritis were first reported in 2015-2016; outbreaks originally presumed to be caused by Neisseria gonorrhoeae ( Ng ). Genomic analysis revealed that the Nm isolates causing these outbreaks were a distinct clade, and had integrated gonococcal DNA at multiple genomic sites, including the gonococcal denitrification apparatus aniA-norB , a partial gonococcal operon of five genes containing isp D, and the acetylglutamate kinase gene argB with the adjacent gonococcal locus NGO0843 . The urethritis isolates had also deleted the group C capsule biosynthesis genes cssA/B/C and csc , resulting in loss of capsule. Collectively, these isolates form the N. meningitidis urethritis clade ( Nm UC). Genomic analysis of recent (2016-2022) Nm UC isolates revealed that the genomic features have been maintained in the clade, implying that they are important for Nm UC's status as a urogenital pathogen. Furthermore, the analysis revealed the emergence of a sub-clade, designated Nm UC-B, phylogenetically separated from the earlier Nm UC-A. This sub-clade has integrated additional gonococcal alleles into the genome, including alleles associated with antimicrobial resistance. Nm UC continues to adapt to a urethral niche and evolve as a urogenital pathogen.

Objectives: Bacterial vaginosis-associated bacterium 2 (BVAB2), Mageeibacillus indolicus and Sneathia spp are highly predictive of bacterial vaginosis (BV) in cisgender women. They have been associated with non-gonococcal urethritis (NGU) in cisgender men in some but not all populations. We evaluated this association in a cross-sectional study of cisgender men who have sex with women only (MSW)., Methods: MSW without gonorrhoea attending a sexual health clinic (SHC) from 2014 to 2018 completed a computer-assisted self-interview, clinical interview and examination. NGU was defined as ≥5 polymorphonuclear leucocytes/high-power field in urethral exudates plus either urethral symptoms or visible discharge. Urine was tested for Chlamydia trachomatis and Mycoplasma genitalium using Aptima (Hologic) and for BVAB2, M. indolicus , Sneathia spp, Trichomonas vaginalis , Ureaplasma urealyticum , Haemophilus influenzae , herpes simplex virus and adenovirus using quantitative PCR., Results: Of 317 MSW age 17-71, 67 (21.1%) had Sneathia spp, 36 (11.4%) had BVAB2, and 17 (5.4%) had M. indolicus at enrolment. Having ≥3 partners in the past 2 months was the only characteristic that was more common among MSW with than those without these bacteria (BVAB2: 47% vs 23%, M. indolicus : 53% vs 24%, Sneathia spp: 42% vs 22%; p≤0.03 for all). One-hundred seventeen men (37%) were diagnosed with NGU at enrolment. There was no significant association of BVAB2, M. indolicus or Sneathia spp with NGU (adjusted OR=0.59, 95% CI 0.14 to 2.43; aOR=3.40, 95% CI 0.68 to 17.06; aOR=0.46, 95% CI 0.16 to 1.27). Of 109 MSW with monthly samples, 34 (31.2%) had one of the bacteria at one or more follow-up visits, 22 of which were co-colonised with >1. Median persistence over 6 months did not differ significantly (BVAB2=30.5 days, IQR=28-87; M. indolicus =87 days, IQR=60-126; Sneathia spp=70 days, IQR=30-135; p≥0.20 for each comparison)., Conclusions: Neither BVAB2, M. indolicus nor Sneathia spp were associated with increased risk of prevalent NGU in MSW attending an SHC., Competing Interests: Competing interests: LEM has received research support and honoraria from Hologic and Nabriva Therapeutics., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

We describe the novel use of oral chloramphenicol for treatment-resistant Mycoplasma genitalium (M. genitalium ) infection in a 20-year-old heterosexual cisgender male presenting with recurrent symptomatic non-gonococcal urethritis. M. genitalium urethritis is an increasingly common clinical conundrum in sexual health clinics and in cases of second-line treatment failure (such as moxifloxacin), UK and international guidelines struggle to make recommendations for third-line treatments. As shown in our case, the evidence base for third-line treatments is lacking, with poor success rates, and may be poorly tolerated. Here we demonstrate the novel use of a well-tolerated oral antimicrobial, chloramphenicol, resulting in rapid microbiological and clinical cure in treatment-resistant M. genitalium urethritis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Mycoplasma penetrans is an emerging pathogen with a reduced genome. This bacterium has only previously been cultured from individuals with chronic immunodeficiencies. Here we report the characteristics of 4 M. penetrans isolates from the urine of immunocompetent males with nongonococcal urethritis, in comparison with strain HF-2 from an immunocompromised patient. Several features exhibited distinct differences between these isolates and HF-2. Unlike HF-2, all 4 were resistant to azithromycin. They exhibited greater sialic acid-dependent binding to erythrocytes, gliding motility speed, and H2O2 production than HF-2. All new isolates produced thinner capsules than HF-2. Invasiveness varied, with some isolates being more invasive than HF-2 and some less invasive. Cytotoxicity to HeLa cells was similar to HF-2, and all strains could clear extracellular traps produced by innate immune cells. We conclude that subtle differences among M. penetrans strains may be critical for this organism to establish an infection in an otherwise healthy individual., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mycoplasma genitalium is an important sexually transmitted pathogen affecting both men and women. Its extremely slow growth in vitro and very demanding culture requirements necessitate the use of molecular-based diagnostic tests for its detection in clinical specimens. The recent availability of U.S. Food and Drug Administration (FDA)-cleared commercial molecular-based assays has enabled diagnostic testing to become more widely available in the United States and no longer limited to specialized reference laboratories. Advances in the knowledge of the epidemiology and clinical significance of M. genitalium as a human pathogen made possible by the availability of molecular-based testing have led to updated guidelines for diagnostic testing and treatment that have been published in various countries. This review summarizes the importance of M. genitalium as an agent of human disease, explains the necessity of obtaining a microbiological diagnosis, describes currently available diagnostic methods, and discusses how the emergence of antimicrobial resistance has complicated treatment alternatives and influenced the development of diagnostic tests for resistance detection, with an emphasis on developments over the past few years.

Background: Mycoplasma genitalium (MG) is associated with urethritis in men and weakly associated with pelvic inflammatory disease in women. Mycoplasma genitalium coinfections with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are commonly reported; however, little is known about their interaction. One study suggested that MG/NG coinfections might increase the bacterial load of NG, which has been shown to have a higher transmission potential. As even less is known about the impact of a simultaneous MG/CT infection, we assessed whether patients with urogenital MG/CT coinfections have a higher bacterial load than patients with a single infection., Methods: There were 1673 urogenital samples from patients from a population-based chlamydia study, and our sexually transmitted infection clinic tested for both CT and MG. When positive, the load was quantified. Nonparametric tests compared the CT and MG load, and linear regression analyses tested the association of the CT and MG load within a patient., Results: In 60 MG-positive patients, MG load ranged from 1.7 to 6.0 log10 copies/ml, similar to the CT load distribution. Only 6 patients were MG-positive and CT-negative, but the MG load distribution was similar to that of CT-positive patients (n.s.). The MG and CT load was unrelated in coinfected persons (n.s.)., Conclusions: We found no correlation between the CT and MG load in urogenital samples, and the MG load distribution was similar in CT-positive and CT-negative patients. These results could have implications for the transmission risk of these infections., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Neisseria meningitidis is a common commensal bacterium found in the respiratory tract, but it can also cause severe, invasive disease. Vaccines have been employed which have been successful in helping to prevent invasive disease caused by encapsulated N. meningitidis from the A, C, W, Y, and B serogroups. Currently, nonencapsulated N. meningitidis groups are more common commensals in the population than in the prevaccine era. One emerging nonencapsulated group of bacteria is the U.S. N. meningitidis urethritis clade (US_NmUC), which can cause meningococcal urethritis in men. US_NmUC has unique genotypic and phenotypic features that may increase its fitness in the male urethra. It is diagnostically challenging to identify and distinguish meningococcal urethritis from Neisseria gonorrhoeae, as the clinical presentation and microbiological findings are overlapping. In this review, the history of meningococcal urethritis, emergence of US_NmUC, laboratory diagnosis, and clinical treatment are all explored.

Nongonococcal urethritis (NGU) is a common genital tract syndrome in men, and up to 50% of cases are considered idiopathic, i.e., no etiological agent is identified. This poses challenges for clinicians in the diagnosis and treatment of NGU and often results in antibiotic misuse and overuse. Therefore, to identify potential infectious causes of urethritis and inform clinical management of urethritis cases, we characterized and compared the urethral microbiota of men with and without idiopathic urethritis. Participants were derived from a case-control study that examined viral and bacterial pathogens and sexual practices associated with NGU. Men with NGU who tested negative for established causes of NGU (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, herpes simplex virus [HSV]-1, and/or HSV-2) were classified as idiopathic cases, and the controls were men reporting no current urethral symptoms. Men provided a urine sample that was used to characterize the urethral microbiota using 16S rRNA gene sequencing. Bacterial taxa associated with idiopathic urethritis were identified using analysis of compositions of microbiomes with bias correction. When stratified by sex of sexual partner, we found that the abundance of Haemophilus influenzae was significantly increased in men who have sex with men with idiopathic urethritis, and the abundance of Corynebacterium was significantly increased in men who have sex with women with idiopathic urethritis. Other taxa, including Ureaplasma, Staphylococcus haemolyticus, Streptococcus pyogenes, Escherichia, and Streptococcus pneumoniae / pseudopneumoniae, dominated the urethral microbiota of idiopathic urethritis cases but not controls, suggesting that these organisms may also contribute to urethritis. Importantly, the taxa we identified represent biologically plausible causes of urethritis and should be prioritized for future study. IMPORTANCE Nongonococcal urethritis (NGU) is the commonest genital tract syndrome in men and is nearly universally presumptively treated with an antibiotic. Common causes of NGU include Chlamydia trachomatis and Mycoplasma genitalium, but in more than 50% of cases, an infectious cause is not identified. In this case-control study, we found that the urethral microbiota composition differed between men with and without idiopathic urethritis and differed by sex of sexual partner. We identified specific bacterial taxa that were associated with idiopathic urethritis, including Haemophilus influenzae and Corynebacterium. These data, together with the finding that key bacterial taxa were found to dominate the urethral microbiota of cases but not controls, suggest that a range of bacteria contribute to urethritis and that these organisms may be influenced by sexual practices. Through identifying the infectious causes of urethritis, we can inform appropriate targeted diagnostic and treatment practices and importantly reduce misuse and overuse of antibiotics.

To investigate the incidence, clinical manifestations, and treatments of gonococcal tysonitis in men. We enrolled men with gonococcal tysonitis and men with gonococcal urethritis from January 2000 to December 2020. Demographic data, interval from non-marital sexual contact to the onset of symptoms of gonococcal tysonitis, occurrence sites, and manifestations were recorded for all patients. Ceftriaxone (1 g) was injected intramuscularly once daily for 5 days in patients with lesions comprising abscesses or nodules. A single dose of ceftriaxone (1 g) was injected intramuscularly in patients with sinus-like lesions. Incision and drainage were performed in patients with non-ruptured abscesses. Fifteen patients with gonococcal tysonitis (0.29%; 95% confidence interval: 0.15-0.44%) were observed among 5087 patients with gonococcal urethritis. The mean age was 38.64 years (range, 17-74 years). The mean gonococcal tysonitis incubation period was 6.02 ± 1.37 days (range, 2-11 days). Lesions were present in the right side of the preputial frenulum in seven patients (46.67%), in the left side of the preputial frenulum in six patients (40%), and in both sides of preputial frenulum in two patients (13.33%). The lesions manifested as abscesses in 7 patients (46.67%), nodules in six patients (40%), and sinus-like lesions in two patients (13.33%); all lesions exhibited tenderness. All 15 patients were cured after treatment. Gonococcal tysonitis is a rare local complication of gonorrhea. Gonococcal urethritis with concurrent gonococcal tysonitis was less common than gonococcal urethritis with concurrent paraurethral gonococcal infection or gonococcal urethritis with concurrent gonococcal epididymitis. Gonococcal tysonitis lesions manifest as abscesses, nodules, and sinus-like lesions. Treatment with ceftriaxone is effective for gonococcal tysonitis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Gonococcal infections with a higher bacterial load may pose a higher risk of transmission. We assessed the association between gonococcal bacterial load and coinfection with Mycoplasma genitalium ., Methods: From September 2015 until May 2018, 200 men and transgender women who have sex with men participated in an HIV pre-exposure prophylaxis (PrEP) demonstration trial in Antwerp, Belgium. They underwent 3-monthly 3-site (anus, urine, and pharynx) molecular testing for N. gonorrhoeae and C. trachomatis and M. genitalium , irrespective of symptoms. Gonococcal bacterial load was determined on remnant DNA extracts using an in-house quantitative PCR. Results were expressed as log 10 transformed copies/mL and analyzed with a linear regression model., Results: Gonococcal bacterial load could be determined for 82 (80.4%) of 102 anal, 17 (73.9%) of 23 urine, and 64 (90.1%) of 71 pharyngeal samples. M. genitalium was detected in five of these anal, two urine, and two pharyngeal samples and C. trachomatis was detected in 16 anal, one urine, and two pharyngeal samples. Gonococcal bacterial load was significantly higher in the presence of M. genitalium (difference 0.92 log copies/mL, 95% CI 0.16-1.67)., Conclusions: Gonococcal bacterial load was higher with M. genitalium coinfection. M. genitalium may thus be a cofactor in gonococcal transmission.

Gonococcal urethritis (GU) is the second most common sexually transmitted infection (STI). Epidemiologic studies of the situation of GU reinfection and its related risk factors among patients with a history of GU in Thailand remain somewhat limited. A hospital-based retrospective cohort study was conducted between January 1, 2010 and December 31, 2020 to determine the incidence and risk factors of GU reinfection among male patients visiting in Royal Thai Army (RTA) Hospitals. A total of 2,465 male patients presenting a history of GU was included in this study. In all, 147 (6.0%; 95% CI 5.1-6.9) male patients presented GU reinfection, representing an incidence rate of 1.3 (95% CI 1.1-1.5) per 100 person-years. The independent risk factors for GU reinfection were age < 30 years (AHR 1.7; 95% CI 1.0-2.8), number of sexual partners equal to 2 (AHR 3.4; 95% CI 1.0-11.2), ≥ 3 (AHR 5.6; 95% CI 2.7-11.6), and participants residing in the north (AHR 4.1; 95% CI 2.3-7.5) and northeast regions (AHR 2.1; 95% CI 1.1-3.9). Incidence of GU reinfection among male patients visiting RTA Hospitals was significantly high among younger aged patients, especially in the north and northeast regions. Multiple sex partners played a major role in GU reinfection. Effective STI prevention programs should be provided to alleviate reinfection and its complications., (© 2021. The Author(s).)

Introduction and Objectives: Pathogens such as Haemophilus spp. have been associated with non-gonococcal urethritis, but their role is unproven. To describe the clinical characteristics and therapeutic outcomes in male patients diagnosed with Haemophilus spp. urethritis., Methods: We carried out a retrospective study of all patients who presented to our hospital (in either the emergency department or the outpatient clinic) between July 2016 and April 2018 in whom Haemophilus spp. was isolated in the urethral samples. We enrolled 30 men with Haemophilus spp.-positive urethritis, including coinfections with Neisseria gonorrhoeae and Chlamydia trachomatis. Clinical, laboratory, demographic, and behavioral data were obtained by reviewing medical histories., Results: The mean age of the patients was 36.6 years (range 21-87). Seventeen patients (63%) reported being exclusively heterosexual. Three patients (10%) were HIV infected, all of them with an undetectable viral load. The most common clinical presentation was mucopurulent urethral discharge, in 13 patients (43%). The antibiotic treatment achieved a complete clinical resolution in 73%., Conclusions: Haemophilus urethritis affected men regardless of their sexual orientation or HIV status. Unprotected oral sex may play a role in its transmission. The limitations of the study preclude verification of the pathogenic role of Haemophilus spp. in acute urethritis, but clinical response after antibiotic treatment suggests that Haemophilus spp. can play such a role., (Copyright © 2020 Asociación Española de Andrología, Medicina Sexual y Reproductiva. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose of Review: Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US&#95;NmUC). This review describes research developments that characterize this urogenital-tropic Nm., Recent Findings: The US&#95;NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US&#95;NmUC urethritis episodes can occur. The US&#95;NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance., Summary: The US&#95;NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Information about the use of flow cytometry in the diagnosis of male urethritis is scarce. The current study aims to evaluate the performance of flow cytometry on first-voided urine in males with infectious urethritis (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis)., Methods: Male patients of the Andrology Centre (Tartu University Hospital, Estonia) were recruited during the period March 2015 -January 2018. Cases included 306 patients with infectious urethritis caused by Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and/or Trichomonas vaginalis. The control group consisted of 192 patients without uro-genital complaints, negative tests for C. trachomatis, N. gonorrhoeae, M. genitalium and T. vaginalis from first-voided urine and no inflammation in first-voided urine, mid-stream urine and urine after prostate massage. C. trachomatis, N. gonorrhoeae, M. genitalium and T. vaginalis were detected from first-voided urine using polymerase chain reaction (PCR) method. First-voided urine was analysed using urine particle analyzer Sysmex UF-500i., Results: The most prevalent infection was chlamydia (64.1%), followed by Mycoplasma genitalium (20.9%), gonorrhoea (7.8%) and trichomoniasis (1.6%). Gonorrhoea caused the highest flow-cytometric leucocyte/bacteria count, followed by chlamydia and Mycoplasma genitalium. Trichomonas vaginalis showed nearly absent inflammation in first-voided urine. Using an empiric flow-cytometry diagnostic threshold for urethritis in first-voided urine (leucocytes ≥ 15/μl and bacteria ≥ 20/μl) the total calculated sensitivity was over 90%. However, when applying such criteria for deciding whether to perform first-voided urine PCR for C. trachomatis, N. gonorrhoeae, M. genitalium and T. vaginalis or not, we could miss 23 cases with infectious urethritis that makes up 7,5% of all proven cases., Conclusions: Flow cytometry of first-voided urine can be considered as a rapid and objective screening method in case of suspected male infectious urethritis., Competing Interests: The authors have declared that no competing interests exist.

Factor H binding protein (FHbp) is an important Neisseria meningitidis virulence factor that binds a negative regulator of the alternative complement pathway, human factor H (FH). Binding of FH increases meningococcal resistance to complement-mediated killing. FHbp also is reported to prevent interaction of the antimicrobial peptide (AMP) LL-37 with the meningococcal surface and meningococcal killing. FHbp is a target of two licensed group B-directed meningococcal (MenB) vaccines. We found a new FHbp variant, peptide allele identification no. 896 (ID 896), was highly expressed by an emerging meningococcal pathotype, the nonencapsulated urethritis clade (US&#95;NmUC). This clade has been responsible for outbreaks of urethritis in multiple U.S. cities since 2015, other mucosal infections, and cases of invasive meningococcal disease. FHbp ID 896 is a member of the variant group 1 (subfamily B), bound protective anti-FHbp monoclonal antibodies, bound high levels of human FH, and enhanced the resistance of the clade to complement-mediated killing in low levels of human complement likely present at human mucosal surfaces. Interestingly, expression of FHbp ID 896 resulted in augmented killing of the clade by LL-37. FHbp ID 896 of the clade was recognized by antibodies elicited by FHbp in MenB vaccines., (Copyright © 2020 American Society for Microbiology.)

Mycoplasma genitalium is a sexually transmitted bacterial pathogen that infects men and women. Antigenic variation of MgpB and MgpC, the immunodominant adherence proteins of M. genitalium, is thought to contribute to immune evasion and chronic infection. We investigated the evolution of mgpB and mgpC sequences in men with non-gonococcal urethritis persistently infected with M. genitalium, including two men with anti-M. genitalium antibodies at enrollment and two that developed antibodies during follow-up. Each of the four patients was persistently infected with a different strain type and each patient produced antibodies targeting MgpB and MgpC. Amino acid sequence evolution in the variable regions of MgpB and MgpC occurred in all four patients with changes observed in single and multiple variable regions over time. Using the available crystal structure of MgpC of the G37 type strain we found that predicted conformational B cell epitopes localize predominantly to the variable region of MgpC, amino acids that changed during patient infection lie in these epitopes, and variant amino acids are in close proximity to the conserved sialic acid binding pocket. These findings support the hypothesis that sequence variation functions to avoid specific antibodies thereby contributing to persistence in the genital tract., Competing Interests: The authors have declared that no competing interests exist.

Male urethritis is an inflammation of the urethra and the periurethral glands; it is widely classified as gonococcal or non-gonococcal. The most frequent microorganisms responsible are Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. In the last three decades, the diagnosis of sexually transmitted diseases depended almost exclusively on traditional methods, such as culture, enzyme immunoassay, fluorescent antibody staining, and hybridization, until the appearance of molecular techniques. Clinical syndromes such as urethritis are rarely specific for a single microorganism, so screening strategies should allow multiple agents to be considered. Multiplex PCR is the fastest and most sensitive technique for the diagnosis of gonococcal and non-gonococcal urethritis. Male urethritis without treatment is one of the main health problems related to reproductive and sexual function, constituting one of the main causes of infertility. The objective of this mini-review was to analyze the epidemiology, causes, diagnosis, and complications of male urethritis., (Copyright © 2020 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Identifying pathogen-specific signs or symptoms of nongonococcal urethritis could improve syndromic management accuracy. We evaluated nongonococcal urethritis signs and symptoms in 220 men with single-pathogen infections (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, or Ureaplasma urealyticum) or idiopathic urethritis. No individual sign or symptom accurately predicted the infectious etiology.

Sitafloxacin (STFX) is an alternative treatment against azithromycin-resistant Mycoplasma genitalium (MG), whereas STFX-resistant MG have appeared recently. Therefore, another antimicrobial regimen for non-chlamydial non-gonococcal urethritis (NGU) is required. Garenoxacin (GRNX) is a fluoroquinolone against respiratory infections, not against urethritis in Japan, but its in-vitro antimicrobial activity against MG is known as similar to or higher than that of moxifloxacin. To clarify the efficiency of GRNX against MG, we examined the clinical efficacy of GRNX for NGU. Seventy-nine male patients with NGU were enrolled and treated with GRNX once daily for 7 days. For assessing microbiological and clinical efficacies, the bacteria including Chlamydia trachomatis (CT), MG, Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) were detected by means of nucleic acid amplification tests before- and after-treatment. After excluded 3 patients, seventy-six patients were evaluated: the median age; 31 (20-61) years, vaginal infection (66%); the most common infectious route and commercial sex worker (43%); the most common source. There were 50 bacteria-positive NGU cases, including 10 multiple bacterial infections. Clinical cure rate was 85.7% (36/42). Detection frequency of each bacterium was similar to the previous reported. The eradication rates of CT, MG, MH, UU and UP were 96.1%, 71.4%, 100%, 85.7% and 100%, respectively. These results indicate that GRNX has the excellent efficacies for NGU except those of MG. Further study of drug-resistant MG urethritis; for instance, studies on the clinical effectiveness of long-term such as 2-week medication of GRNX or the efficacy of alternative treatment regimens are necessary., Competing Interests: Declaration of Competing Interest Hiroshi Kiyota and Hiroki Yamada received donations from Toyama Chemical Co., Ltd., Taisho Toyama Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., TAIHO Pharmaceutical Co., Ltd., Astellas Pharma inc. and Sanofi K.K. Shin Egawa received research fund from Foundation for Biomedical Research and Innovation and Olympus Corporation, received donations from Astellas Pharma, Takeda Pharmaceutical Co., Ltd. and Fujifilm RI Pharma Co., Ltd., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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&#95;NmUC). However, no cultivation-independent tests are available for the US&#95;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&#95;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&#95;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&#95;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&#95;NmUC clade., Competing Interests: The authors have declared that no competing interests exist.

In 2015, we identified a non-groupable clade of Neisseria meningitidis that causes urethritis in men (the US&#95;NmUC). Because repeat infection is common with Neisseria gonorrhoeae, we examined whether reinfection also occurs with the US&#95;NmUC. We provide evidence that men are susceptible to repeat episodes of urethritis from the US&#95;NmUC.

Background: Male urethritis is primary sexually transmitted. Northern Territory (NT) has the highest rates of gonococcal infection in Australia and local guidelines recommend empiric treatment with azithromycin and ceftriaxone for all men presenting with urethritis. As gonococcal drug resistance is a growing concern, this study aims to improve empiric use of ceftriaxone through examining local patterns of male urethritis, comparing cases of gonococcal urethritis (GU) to controls with non-gonococcal urethritis (NGU)., Methods: A retrospective study was undertaken of all men with symptomatic urethritis presenting to Darwin sexual health clinic from July 2015 to July 2016 and aetiology of urethritis in this population was described. Demographic, risk profile, and clinical features of GU cases were compared to NGU controls., Results: Among n = 145 men, the most common organisms identified were Chlamydia trachomatis (23.4%, SE 3.5%) and Neisseria gonorrhoeae (17.2%, SE 3.1%). The main predictors of GU were any abnormalities on genital examination (aOR 10.4, 95% CI 2.1 to 50.8) and a history of urethral discharge (aOR 5.7, 95% CI 1.4 to 22.6). Aboriginal patients (aOR 3.0, 95% CI 0.9 to 9.6) and those over 30 years of age (aOR 1.4, 95% CI 0.3 to 7.0) were more likely to have GU in the unadjusted analysis, but not in the adjusted model., Conclusion: This is the first study looking at patterns of male urethritis in urban NT and the results support a move towards adopting national guidelines to use ceftriaxone for empiric management of syndromic urethritis only in high-risk patients. In addition to traditional demographic risk factors, clinical features remain an important component of risk stratification.

Competing Interests: Competing interests: We have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare.

Urine is an acceptable, non-invasive sample for investigating the human urogenital microbiota and for the diagnosis of sexually transmitted infections. However, low quantities of bacterial DNA and PCR inhibitors in urine may prevent efficient PCR amplification for molecular detection of bacteria. Furthermore, cold temperatures used to preserve DNA and bacteria in urine can promote precipitation of crystals that interfere with DNA extraction. Saline, Dulbecco's Phosphate Buffered Saline, or Tris-EDTA buffer were added to urine from adult men to determine if crystal precipitation could be reversed without heating samples beyond ambient temperature. Total bacterial DNA concentrations and PCR inhibition were measured using quantitative PCR assays to compare DNA yields with and without buffer addition. Dissolution of crystals with Tris-EDTA prior to urine centrifugation was most effective in increasing bacterial DNA recovery and reducing PCR inhibition. DNA recovery using Tris-EDTA was further tested by spiking urine with DNA from bacterial isolates and median concentrations of Lactobacillus jensenii and Escherichia coli 16S rRNA gene copies were found to be higher in urine processed with Tris-EDTA. Maximizing bacterial DNA yield from urine may facilitate more accurate assessment of bacterial populations and increase detection of specific bacteria in the genital tract., Competing Interests: LEM has received donations of test kits, equipment, reagents, and speaking honoraria from Hologic Incorporated. The company had no role in the research presented in this paper and this does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors report no conflicts of interest.

Objective: To investigate the status quo of the diagnosis and treatment of male urethritis (MU) in urology and andrology., Methods: According to The Guidelines for Clinical Diagnosis and Treatment of Sexually Transmitted Diseases (2017), we designed 27 questions on the prevalence, diagnosis, treatment, and prognosis of MU. Using these questions, we conducted a questionnaire investigation among urological, andrological and other relevant clinicians with different professional titles, followed by an analysis of the compliance of the doctors to the Guidelines., Results: Totally, 116 valid questionnaires were collected from 86 urological, 28 andrological and 2 other relevant doctors, including 22 professors, 36 associate professors, 40 attending doctors and 16 resident doctors. MU was found mostly in those aged 20－40 years and more than half of the patients had a history of unclean sex, gonococcal urethritis significantly less prevalent than non-gonococcal, with Ureaplasma urealyticum as the most common pathogen of non-gonococcal urethritis. As for the compliance to the Guidelines in the diagnosis of MU, 22.73% of the professors, 16.67% of the associate professors, 15.00% of the attending doctors and 12.50% of the resident doctors examined the eyes, mouth and perianus (P > 0.05), 40.91% of the professors, 58.33% of the associate professors, 40.00% of the attending doctors and 37.50% of the resident doctors conducted HIV and syphilis screening (P > 0.05), and 86.36% of the professors, 77.78% of the associate professors, 70.00% of the attending doctors and 75.00% of the resident doctors performed genital mycoplasma screening (P > 0.05). Concerning the treatment of MU, 50.00% of the professors, 47.22% of the associate professors, 22.50% of the attending doctors and 43.75% of the resident doctors used anti-Chlamydia trachomatis drugs for gonococcal urethritis (P > 0.05), 0.00% of the professors, 11.11% of the associate professors, 5.00% of the attending doctors and 31.25% of the resident doctors prescribed 1g single-dose oral azithromycin for non-gonococcal urethritis (P < 0.05), 13.64% of the professors, 33.33% of the associate professors, 17.50% of the attending doctors and 6.25% of the resident doctors medicated persistent or recurrent non-gonococcal urethritis for >4 weeks (P > 0.05), 63.64% of the professors, 83.33% of the associate professors, 57.50% of the attending doctors and 62.50% of the resident doctors treated asymptomatic trachomatis and mycoplasma infections according to the proposed medication in the Guidelines (P > 0.05). As regards the results of treatment, the cure rate of gonococcal urethritis was 100.00% by professors, 97.22% by associate professors, 95.00% by attending doctors and 81.25% by resident doctors (P > 0.05), and that of non-gonococcal urethritis was 86.36% by professors, 61.11% by associate professors, 62.50% by attending doctors and 37.50% by resident doctors (P < 0.05)., Conclusions: Urological and andrological clinicians do not strictly follow the Guidelines in the diagnosis and treatment of male urethritis. There are significant differences in the dosing of azithromycin and results of treatment of non-gonococcal urethritis among doctors with different professional titles, but not in the other aspects.

Background: Mycoplasma genitalium was previously less common among men who have sex with men (MSM) compared with men with only female partners (MSW) in men with nongonococcal urethritis (NGU) in Sydney, Australia. We aimed to determine the prevalence of M. genitalium and of macrolide-resistant M. genitalium in men with NGU and to compare differences between prevalence and resistance rates between MSM and MSW., Methods: We enrolled 588 men with NGU in a prospective study at two urban sexual health services. The ResistancePlus MG assay (SpeeDx, Australia) was used to detect both M. genitalium, and macrolide resistance-associated mutations in first-void urine samples. Demographic, behavioral and clinical data were analyzed to investigate associations with M. genitalium infection or the presence of macrolide resistance., Results: Mycoplasma genitalium prevalence was 12.8% (75 of 588) overall and among MSM (12.8% [39 of 306]) and MSW (12.8% [36 of 282]; risk ratio [RR], 1.00; 95% confidence interval [CI], 0.65-1.52). Overall, 70.7% (53 of 75) of M. genitalium strains were macrolide-resistant, with significantly more resistance among MSM (89.7%, 35 of 39) than MSW (50%, 18 of 36) (RR, 1.80; 95% CI, 1.27-2.54; P = 0.001). On multivariate analysis, the presence of M. genitalium macrolide resistance mutations was independently associated with having male sexual partners compared with having only female partners (RR, 1.55; 95% CI, 1.02-2.38; P = 0.042)., Conclusions: Prevalence of M. genitalium among men with NGU is now similar for MSW and MSM and has increased locally from 5.2% to 12.8% within the last 10 years. Men who have sex with men are significantly more likely than MSW to harbor macrolide-resistant M. genitalium infections. This has treatment implications.

Ureaplasma spp. are a genus of bacteria for which two human-associated species exist: Ureaplasma urealyticum and Ureaplasma parvum Their definition as a pathogen in the context of nongonococcal urethritis (NGU) and infertility among males remains highly controversial, largely due to historically high rates of isolation of these bacteria from the urethra of seemingly healthy men. This review summarizes the emerging evidence suggesting a true pathogenic role of these bacteria under specific conditions, which we term risk factors. We examine the historical, clinical, and experimental studies which support a causal role for Ureaplasma spp. in the development of NGU as well as some of the proposed mechanisms behind the association of Ureaplasma spp. and the development of infertility. Finally, we discuss the potential for developing a case-by-case risk-based approach toward the management of men who present with seemingly idiopathic NGU but who are positive for Ureaplasma spp., (Copyright © 2019 American Society for Microbiology.)

Background: In a context of increasing use of Nucleic Acid Amplification Test, diagnoses of Neisseria gonorrhoeae and Chlamydia trachomatis infections among men increased in Europe and USA since 2007. We aimed to describe trends in the incidence of male urethritis in France between 2007 and 2017., Methods: We analysed male urethritis clinical cases reported by the French GPs' Sentinelles network., Results: GPs reported 1944 cases of male urethritis during the study period. The estimated annual incidence rates in men aged 15 years and older remained stable between 226 cases per 100,000 seen in 2007 and 196 in 2017 (P value = 0.9). A third-generation cephalosporin with macrolide or tetracycline was prescribed in 17.5% of cases in 2009 (27/154) and 32.4% in 2017 (47/145) (P value = 0.0327)., Conclusions: The incidence rates for adult male urethritis diagnosed in primary care have remained stable since 2007 in France in contrast with the increasing trend of Neisseria gonorrhoeae and Chlamydia trachomatis infections based on microbiological surveillance. Using stable clinical definition for male urethritis seems essential to follow correctly epidemiological dynamic.

Background: Although Mycoplasma genitalium (MG) is an acknowledged cause of nongonococcal urethritis (NGU), access to diagnostic testing is limited. Syndromic management is common, yet little is known about natural history., Methods: Between August 2014 and April 2016, 13 heterosexual men aged ≥16 years with MG were identified within a cohort study of men with and without NGU attending an urban sexually transmitted diseases clinic. Men had 6-7 monthly visits. NGU was defined as ≥5 polymorphonuclear leukocytes per high-power field on urethral Gram stain plus either visible urethral discharge or urethral symptoms. Men with NGU received 1 g of azithromycin. Men with persistent NGU received moxifloxacin 400 mg for 14 days. First-void urine was retrospectively tested for MG using transcription-mediated amplification. Resistance-associated mutations were detected by polymerase chain reaction (PCR) and sequencing. Organism load was determined by quantitative PCR., Results: Sixty-two percent of MG-positive men had macrolide resistance-mediating mutations (MRMM) at enrollment; 31% had parC mutations (all outside the quinolone resistance-determining region). MG persisted after azithromycin in 7 men, 6 of whom had MRMM. The median duration of persistence in the absence of curative therapy was 143 days (range, 21-228). Five men experienced symptom resolution after azithromycin, but MG persisted for another 89-186 days before moxifloxacin. Organism load was somewhat lower in MRMM than wild-type infections (P = .16)., Conclusions: The high prevalence of macrolide resistance and long duration of infection after symptom resolution highlights the need for diagnostic MG testing of men with NGU to direct therapy., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Non-gonococcal urethritis (NGU) is the most common disease of the genital tract in men. Recent studies have recommended avoiding the empiric antibiotic administrations that constitute the classical treatment approach in NGU and to aim toward treatment of causative pathogens. However, the classification of NGU agents remains controversial. In addition, the relevance of the commensalism of Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, and Gardnerella vaginalis, which are among the opportunistic pathogens found in the urethral flora, has yet to be determined. Furthermore, there are certain pathogens on which sufficient studies have not been conducted, although they are known to be NGU pathogens, and their statuses should be updated. In this review, the classification of NGU pathogens is summarized in the light of the current literature.

Purpose: To study the sexual behavior and status of sexually transmitted urethritis (STU) in the elderly population of South Korea., Materials and Methods: Congregating places for elderly population, which were selected on the expected risk of sexually transmitted infections, were visited to study their sexual behavior, awareness on sexually transmitted diseases (STDs), and STU status using a specially developed survey and urine polymerase chain reaction (PCR) test. In addition, analysis of the Health Insurance Review & Assessment Service (HIRA) database was done to study the nationwide status and trends of STU of the elderly population., Results: The study found that approximately 42% of elderly South Koreans were sexually active. Elderlies in the high-risk group showed a higher percentage of multiple sexual partners and prostitution than elderlies in the low-risk group. Only 3% and 14% in the low-risk group and high-risk group used condoms, showing a very low rate of condom use. Both the urine PCR results and HIRA database analysis showed that the prevalence of STU was not high and it remained stable in recent years, implying that currently, STU is not a significant burden on public health in the elderly population of South Korea., Conclusions: The current study presented the sexual behavior in the elderly population of South Korea, as well as the recent prevalence and trend of STU in the elderly population. These results may be used as baseline data for future study, education, prevention and public campaign plan for STDs in the elderly population., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

The predominance of the genus Corynebacterium in the healthy male urogenital system contributes to the resident microbiome of not only the distal urethra, but potentially the proximal urethra and urinary bladder as well. However, for certain species in this genus, pathogenic potential was described, and the salient representative is Corynebacterium glucuronolyticum (C. glucuronolyticum) implicated in cases of urethritis and prostatitis in men. Nonetheless, some still question whether C. glucuronolyticum can actually be considered pathogenic or rather just a commensal species fortuitously isolated in patients with urogenital symptoms and/or syndromes. Although pathogen/commensal dichotomy is not always clear-cut, we hypothesize that specific genetic markers may expose C. glucuronolyticum as a convincingly pathogenic Corynebacterium. More specifically, characteristic pathogenic gene constellation inherent to this species (most notably the presence of specific sortase/SpaA-type pili gene clusters, but also the augmentative role of type VII secretion system) may significantly facilitate host tissue adhesion, with subsequent suppression/evasion of the immune response and acquisition of vitally important nutrients. Consequently, these genetic markers differentiate C. glucuronolyticum from its commensal counterparts, and give this species a pathogenic facet, which can be even further influenced by the Allee effect. In this paper we also propose a specific methodological approach on how to analyze C. glucuronolyticum epithelial colonization capacity and explore inceptive host cell-pathogen interactions that manipulate host environment and immune responses. This entails moving from approaches based primarily on overall homology of primary sequences towards specific structure-function studies to precisely evaluate all stakeholders involved in pili assemblage, cell adhesion and the expression of other virulence traits. In the era of high precision medicine, the hypothesized roles of C. glucuronolyticum adhesion systems in both virulence and nutrient acquisition may also reveal promising targets for future drug developments., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Although Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) are major causes of non-gonococcal urethritis (NGU), up to 50% of cases are of unknown aetiology. We sought to identify urethral exposures at last sexual episode associated with NGU and non-CT/non-MG NGU to identify anatomical sites from which aetiologically relevant micro-organisms may be acquired., Methods: We enrolled STD clinic patients with and without NGU assigned male sex at birth and age ≥16 into a cross-sectional study. NGU was urethral symptoms or visible discharge plus ≥5 polymorphonuclear leucocytes without Neisseria gonorrhoeae . Urine was tested for CT and MG (Aptima). We used logistic regression to estimate the association between urethral exposures at last sex and NGU separately among cisgender men and transgender women who have sex with men (MSM/TGWSM) and cisgender men who have sex with women (MSW)., Results: Between 8 August 2014 and 1 November 2017, we enrolled 432 patients, including 183 MSM/TGWSM (118 NGU+, 65 NGU-) and 249 MSW (126 NGU+, 123 NGU-). The mean age was 34; 59% were white. CT and MG were detected in 72 (30%) and 49 (20%) NGU+ participants, respectively. Compared with MSM/TGWSM reporting only non-urethral exposures at last sex, those reporting insertive anal intercourse (IAI) only (adjusted OR (AOR)=4.46, 95% CI 1.09 to 18.19) and IAI with insertive oral sex (IOS) (AOR=7.88, 95% CI 2.67 to 23.26) had higher odds of NGU. MSM/TGWSM reporting IOS only had no significant increased odds (AOR=1.67, 95% CI 0.58 to 4.85). Compared with MSW whose only urethral exposure at last sex was vaginal sex (VS), MSW reporting IOS and VS had similar odds of NGU (OR=0.84, 95% CI 0.50 to 1.41). The results were similar for non-CT/non-MG NGU., Conclusions: Among MSM/TGWSM, IAI may lead to transmission of yet-unidentified rectal micro-organisms that cause non-CT/non-MG NGU, in addition to transmission of known pathogens. Sites of urethral exposure appear less important for understanding NGU risk among MSW due to minimal variation in behaviour., Competing Interests: Competing interests: CMK and LEM have received donations of test kits and reagents from Hologic. All other authors declare that they have no conflict of interest., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)