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Mycoplasma genitalium (MG) is an important sexually transmitted pathogen that can cause urethritis in males and pelvic inflammatory disease in females. Due to its complex growth requirements and lengthy incubation times, culturing MG in clinical laboratories is impractical. Here we describe a rapid and visual assay combining recombinase polymerase amplification (RPA) with lateral flow (LF) strips to detect MG (MG-RPA-LF). The limit of detection (LoD) of this method was 33.6 genome equivalents (GE) per reaction, using a dilution series of purified genomic DNA. Clinical performance was evaluated by testing 100 urogenital swabs. Compared to the Simultaneous Amplification and Testing assay, our MG-RPA-LF assay showed a sensitivity of 94 % (95 % CI, 82 %-98 %) and a specificity of 100 % (95 % CI, 91 %-100 %). The overall concordance between the two methods was 97 % (95 % CI, 91 %-99 %) with a κ coefficient of 0.94 (P < 0.001). Without cumbersome and expensive instruments, this method is anticipated to be a promising alternative to diagnose MG infection, especially in resource-poor settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

Objectives: While Mycoplasma genitalium is reported as a common rectal infection among men who have sex with men (MSM), published data refer predominantly to urethral infections. Currently, most guidelines recommend M. genitalium testing from urine in men with symptomatic, non-gonococcal urethritis. Macrolide resistance-associated mutations (MRMs) among M. genitalium have increased during the last decade especially among MSM. We aim to demonstrate the prevalence and anatomical distribution of M. genitalium infection and MRM in urine and rectal specimens among MSM in Sweden., Methods: In this cross-sectional study in 2019, paired urine and rectal samples from symptomatic and asymptomatic MSM attending a sexually transmitted infection clinic in the south of Sweden were screened for M. genitalium , presence of MRM, Neisseria gonorrhoeae , Chlamydia trachomatis , HIV and syphilis., Results: The overall prevalence of M. genitalium was 10.5% (64 of 609), rectal samples 7.6% (46 of 609) and urine samples 3.9% (24 of 609) (p=0.007). Among M. genitalium -positive cases, single rectal and single urethral infection was detected in 62.5% (40 of 64) and 28.1% (18 of 64), respectively (p<0.0001). Infection at both sites was seen in 9.4% (6 of 64). The prevalence of MRM was 67.9% (19 of 28). M. genitalium was significantly associated with HIV (OR 2.60, 95% CI 1.14 to 5.88, p=0.02). Among the MSM, 7.4% (45 of 609) were infected with N. gonorrhoeae, 6.7% (41 of 609) with C. trachomatis , 7.1% (43 of 609) with HIV and 0.7% (4 of 609) with syphilis., Conclusions: In this study, among MSM, most infections with M. genitalium were detected as rectal mono infections. The prevalence of M. genitalium among MSM was almost twofold higher in rectal samples (7.6%) compared with urine samples (3.9%). The prevalence of macrolide resistance was high with no difference between urine and rectal samples., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current clinical care for common bacterial STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG)) involves empiric antimicrobial therapy when clients are symptomatic, or if asymptomatic, waiting for laboratory testing and recall if indicated. Near-to-patient testing (NPT) can improve pathogen-specific prescribing and reduce unnecessary or inappropriate antibiotic use in treating sexually transmitted infections (STI) by providing same-day delivery of results and treatment., Methods: We compared the economic cost of NPT to current clinic practice for managing clients with suspected proctitis, non-gonococcal urethritis (NGU), or as an STI contact, from a health provider's perspective. With a microsimulation of 1000 clients, we calculated the cost per client tested and per STI- and pathogen- detected for each testing strategy. Sensitivity analyses were conducted to assess the robustness of the main outcomes. Costs are reported as Australian dollars (2023)., Results: In the standard care arm, cost per client tested for proctitis, NGU in men who have sex with men (MSM) and heterosexual men were the highest at $247.96 (95% Prediction Interval (PI): 246.77-249.15), $204.23 (95% PI: 202.70-205.75) and $195.01 (95% PI: 193.81-196.21) respectively. Comparatively, in the NPT arm, it costs $162.36 (95% PI: 161.43-163.28), $158.39 (95% PI: 157.62-159.15) and $149.17 (95% PI: 148.62-149.73), respectively. Using NPT resulted in cost savings of 34.52%, 22.45% and 23.51%, respectively. Among all the testing strategies, substantial difference in cost per client tested between the standard care arm and the NPT arm was observed for contacts of CT or NG, varying from 27.37% to 35.28%., Conclusion: We found that NPT is cost-saving compared with standard clinical care for individuals with STI symptoms and sexual contacts of CT, NG, and MG., Competing Interests: Declaration of Competing Interest CSB and CKF were supported by an Australian National Health and Medical Research Council Leadership Investigator Grant (GNT1173361 and GNT1172900, respectively). JJO and EPFC are supported by an Australian National Health and Medical Research Council Emerging Leadership Investigator Grant (GNT1193955 and GNT1172873). YZ is supported by an Australian Government Research Training Program (RTP) scholarship. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 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 ( M. genitalium ) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide ( 23S rRNA gene) and fluoroquinolone ( parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period ( p = 0.010), but this was not evident for azithromycin resistance ( p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections.

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&#95;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&#95;NmUC, designated as the Japan N. meningitidis urethritis clade (J&#95;NmUC). The subtypes were characterized by PCR, serologic testing, and whole-genome sequencing. Our study suggests that an ancestor of US&#95;NmUC and J&#95;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&#95;NmUC), which can cause meningococcal urethritis in men. US&#95;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&#95;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.)

Background: In a previous study of men attending Melbourne Sexual Health Centre who had Neisseria gonorrhoeae detected by urine Aptima Combo 2 (AC2) testing, 11% were asymptomatic. This study aimed to determine whether N. gonorrhoeae can be cultured from asymptomatic men screening positive for N. gonorrhoeae by nucleic acid amplification testing (NAAT) of urine., Methods: Between 1 July 2017 and 31 March 2019, all men attending Melbourne Sexual Health Centre were tested for N. gonorrhoeae by AC2 testing of urine whether urethral symptoms were reported or not. NAAT-positive men were recalled and a urethral swab performed for gonococcal culture using modified Thayer-Martin media with determination of minimum inhibitory concentrations (MICs) by agar dilution., Results: There were 1001 cases (860 individuals) positive for N. gonorrhoeae by urine AC2: 892 (89%) reported urethral symptoms; 109 (11%) did not. Twenty-five asymptomatic cases were excluded because of antibiotic use at or following screening. Of the remaining 84 asymptomatic men, 41 (49%) had a urethral swab performed a median of 5 days after screening. Twenty-one men had urethral discharge at the return visit, 11 of whom reported the discharge at the return visit. Of the 41 men who were swabbed, 31 (76%; 95% CI 60% to 88%) were culture positive for N. gonorrhoeae . Among the 21 men who subsequently developed discharge, 19 (90%; 95% CI 70% to 99%) were culture positive. Among the 20 men who remained asymptomatic, 12 (60%; 95% CI 36% to 81%) were culture positive. MIC profiles were obtained from all isolates., Conclusions: Gonorrhoea was isolated in most but not all asymptomatic men screening positive for N. gonorrhoeae by urine NAAT. Clinicians should consider performing urethral culture in such men to ensure optimal surveillance for antimicrobial resistance. Isolation of N. gonorrhoeae by culture in men without discharge indicates these are true infections with viable organisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Urethritis refers to inflammation of the urethra and is classified as gonococcal (caused by Neisseria gonorrhoeae) or nongonococcal in origin (most commonly caused by Chlamydia trachomatis, Mycoplasma genitalium, or Trichomonas vaginalis). The most common signs and symptoms include dysuria, mucopurulent urethral discharge, urethral discomfort, and erythema. Diagnostic criteria include typical signs, symptoms, or history of exposure in addition to mucopurulent discharge, Gram stain of urethral secretions showing at least two white blood cells per oil immersion field, first-void urinalysis showing at least 10 white blood cells per high-power field, or a positive leukocyte esterase result with first-void urine. First-line empiric treatment consists of ceftriaxone and doxycycline; however, the antibiotic regimen may be targeted to the isolated organism. Repeat testing is not recommended less than three weeks after treatment because false-positive results are possible during this time. Patients treated for a sexually transmitted infection should have repeat screening in three months, with shared decision-making about future screening intervals. Patients treated for urethritis should abstain from sex for seven days after the start of treatment, until their partners have been adequately treated, and until their symptoms have fully resolved.

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.)

We report a case of Mycoplasma genitalium -positive non-gonococcal urethritis who failed to respond to multiple different courses of antibiotics including azithromycin, minocycline, moxifloxacin and spectinomycin. Extracted M. genitalium DNA from urethral swabs obtained from the patient harbored mutations of 23S rRNA, parC and gyrA . Microbiological cure was eventually achieved by a 14-day course of doxycycline.

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.

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.

Haemophilus parainfluenzae (HPAR) is a Gram-negative bacterium that can become an opportunistic urogenital pathogen. Recently, multidrug resistant (MDR) strains have emerged. We aim to analyse the epidemiology of HPAR at Hospital Universitari de Bellvitge between 2013 and 2017 to determine its putative role in sexually transmitted infections (STI). Strains were classified by sample origin, and antimicrobial susceptibility was performed by disk-diffusion tested on Mueller-Hinton Fastidious. MDR was defined as the resistance of the antimicrobial to three or more antibiotic class. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) after restriction with SmaI and Cfr9I. We classified 944 HPAR isolates as being of urogenital (n = 175; 18.5%), respiratory (n = 719; 76.2%), or other (n = 50; 5.3%) origins. Among the urogenital isolates, 50 (28.6%) were MDR, which was significantly higher than that found in respiratory samples (40/719; 5.6%; p < 0.01). The frequency of MDR increased progressively among urogenital samples from 13.3% (2013) to 33.3% (2017) (r = 0.8; p = 0.035). The resistance rates for all 944 episodes were significantly higher for cotrimoxazole (51.4%), tetracycline (46.3%), chloramphenicol (28.0%), ciprofloxacin (21.1%), and ampicillin (20.6%). After PFGE, no clonal relationship was found. Clinical charts were available for 40 symptomatic patients with MDR HPAR infections presenting mostly urethritis (n = 26; 65.0%). In all cases, symptoms were treated effectively with combination therapy. Furthermore, in 10 of those patients with urethritis, MDR HPAR was the only potential pathogen to be identified. The emergence of MDR HPAR is a matter of concern, and the detection as a single pathogen highlights its putative role as cause of STI.

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.

Mycoplasma genitalium was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. It is a sexually transmitted bacterium associated with a number of urogenital conditions in women like cervicitis, endometritis, pelvic inflammatory disease, infertility, and susceptibility to human immunodeficiency virus (HIV). However, M. genitalium may also act like a stealth pathogen at female reproductive tract, giving no symptoms. Its prevalence varies between different groups, with the average being 0.5-10% in the general population and 20-40% in women with sexually transmitted infections. The recommended treatment of this infection is azithromycin as a single 1-g dose. However, in recent years, macrolide resistance has increased which is significantly lowering the cure rate, being less than 50% in some studies. New treatment regimens need to be investigated due to increasing drug resistance. The discussion and suggestion of an algorithm for management of this infection is the highlight of this paper.

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.

Mycoplasma genitalium is a fastidious organism of the class Mollicutes, the smallest prokaryote capable of independent replication. First isolated in 1981, much is still unknown regarding its natural history in untreated infection. It is recognized as a sexually transmitted pathogen causing acute and chronic non-gonococcal urethritis (NGU) in men, with a growing body of evidence to suggest it also causes cervicitis and pelvic inflammatory disease in women. Its role in several other clinical syndromes is uncertain. The majority of people infected remain asymptomatic and clear infection without developing disease; asymptomatic screening is therefore not recommended. Prevalence rates are higher in patients attending sexual health clinics and in men with NGU. Limited availability of diagnostics has encouraged syndromic management, resulting in widespread antimicrobial resistance and given that few antimicrobial classes have activity against M. genitalium , there is significant concern regarding the emergence of untreatable strains. There is a need for wider availability of testing, which should include detection of macrolide resistance mediating mutations. Expertise in interpretation of microbiological results with clinical correlation ensures targeted treatment avoiding unnecessary antibiotic exposure. Public health surveillance nationally and internationally is vital in monitoring and responding to changing epidemiology trends. In this review, we summarize current knowledge of M. genitalium , including epidemiology, clinical and microbiological data, and discuss treatment challenges in the era of rising multidrug resistance.

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.