Nongonococcal Urethritis In Men Research Articles

Mycoplasma genitalium: A new superbug.

Mycoplasma genitalium (MG) is an emerging sexually transmitted pathogen. It is an important cause of nongonococcal urethritis in men and is associated with cervicitis and pelvic inflammatory disease in women, putting them at risk of infertility. Multiple factors that aid pathogenesis of MG include its ability of adhesion, gliding motility, and intracellular invasion by means of the tip organelle. Through intracellular localization and antigenic variation, MG could result in treatment-resistant chronic infection. There are limited data on the prevalence of MG in Indian patients with urogenital syndromes. Recently, a high prevalence of extra genital infection with MG has been reported. Molecular assays are the major diagnostic techniques of MG infection. Antimicrobial agents such as macrolides, along with fluoroquinolones, are the treatment of choice for MG infections. The issue of drug resistance to azithromycin and fluoroquinolones in MG is rising globally. As molecular tests are becoming available for MG, both for the diagnosis and the detection of antimicrobial resistance, any patient with MG infection should then be tested for antimicrobial resistance. Consideration of MG as a cause of sexually transmitted disease in the Indian population is crucial in diagnostic algorithms and treatment strategies. The purpose of this review is to understand the prevalence of MG in different clinical scenarios, molecular mechanisms of pathogenesis, current status of antimicrobial resistance, and its impact on MG treatment.

Mycoplasma genitalium and sexually transmitted infections: evidences and figures in a tertiary hospital.

IntroductionMycoplasma genitalium is an emerging cause of sexually transmitted infections (STIs) and has been implicated in non-gonococcal urethritis in men and cervicitis in woman. The aim of this study is determinate the incidence and pathogenicity of M. genitalium within the diagnosis of STIs detected from clinical samples in a third level hospital.Material and methodsA total of 8,473 samples from endocervix, urethra, vagina, rectum and others were processed applying Allpex STI Essential Assay. More than 190 records were reviewed to determinate M. genitalium pathogenicity.ResultsM. genitalium was detected in a rate 2.8%. Co-infections were detected in 20% of the patients.ConclusionsM. genitalium is considered a STI emerging pathogen thanks to the renewal of multiplex-PCR tests although with a low incidence in our approach. Emerging from our experience and the institutional recommendations both detection of acid nucleic techniques (NAATs) and gonococcal culture might be implemented accurately and coexist to adequate prescriptions.

Computational identification of putative common genomic drug and vaccine targets in Mycoplasma genitalium

Mycoplasma genitalium is an obligate intracellular bacterium that is responsible for several sexually transmitted infections, including non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women. Here, we applied subtractive genomics and reverse vaccinology approaches for in silico prediction of potential vaccine and drug targets against five strains of M. genitalium. We identified 403 genes shared by all five strains, from which 104 non-host homologous proteins were selected, comprising of 44 exposed/secreted/membrane proteins and 60 cytoplasmic proteins. Based on the essentiality, functionality, and structure-based binding affinity, we finally predicted 19 (14 novel) putative vaccine and 7 (2 novel) candidate drug targets. The docking analysis showed six molecules from the ZINC database as promising drug candidates against the identified targets. Altogether, both vaccine candidates and drug targets identified here may contribute to the future development of therapeutic strategies to control the spread of M. genitalium worldwide.

1532. Demographics and Population Epidemiology of Mycoplasma genitalium infection: Correlation to Co-Infection and prior STI history

BackgroundDespite reports in the past few years that Americans are having less sex, the US Centers for Disease Control and Prevention (CDC) recently reported in 2019 that sexually transmitted infection (STI) cases are at an all-time high in the United States. The CDC report included statistics on confirmed cases of Chlamydia trachomatis and Neisseria gonorrhoeae, but did not include data for Trichomonas vaginalis and Mycoplasma genitalium. Although Trichomonas vaginalis and Mycoplasma genitalium are generally recognized agents responsible for STI’s, there is limited prevalence data in the United States.MethodsHerein we present STI prevalence and socio-demographic epidemiological data associated with patients enrolled in a multicenter STI study using the automated multiplex qualitative CE marked assay, Alinity m STI. The enrolled study population reflected a diverse number of participants with an approximately equal male to female ratio, prior STI history, single and married, education levels from primary to post-graduate, as well as different ethnicities.ResultsParticipants in this study population who have previously been diagnosed with an STI had an overall Mycoplasma genitalium prevalence rate that was approximately double those who have not been previously diagnosed with an STI. Furthermore, the co-infection rate for Mycoplasma genitalium and Trichomonas vaginalis was as high as 2.5% for vaginal swab specimens with an overall Mycoplasma genitalium prevalence of 11.6%. The overall prevalence of Trichomonas vaginalis in women was 12.3%. Neisseria gonorrhoeae had the lowest overall prevalence in men and women at 2.4%, and Chlamydia trachomatis at had an overall prevalence of 9.8%.ConclusionMycoplasma genitalium infections are generally asymptomatic in both men and women that contributes to up to 35% of non‐chlamydial non‐gonococcal urethritis in men and linked to cervicitis and pelvic inflammatory disease in women. Left untreated or not accurately diagnosed, STIs can cause significant, serious long-term health consequences including sexual, reproductive, and psychological well-being that present an extensive challenge and burden to public health in the United States.DisclosuresJose Santiago, PhD, Abbott (Employee)

Clinical features of nongonococcal urethritis in men associated with the presence of bacterial vaginosis in their sexual partners

Clinical features of nongonococcal urethritis in men associated with the presence of bacterial vaginosis in their sexual partners

Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study

ObjectivesChlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case–control studies that examined the...

Detection of ureaplasmas and bacterial vaginosis associated bacteria and their association with non-gonococcal urethritis in men.

No aetiology is found in up to 40% of men with symptomatic urethritis. Male partners of women with bacterial vaginosis (BV) may be at higher risk of non-gonococcal urethritis (NGU). The aim of this study was to examine the role of BV associated bacteria in first-void urine (FVU) in 97 asymptomatic men without urethritis (controls) and 44 men (cases) with NGU including 20 men with idiopathic urethritis (IU) attending a Swedish STD-clinic between January and October 2010. BV-associated bacteria and ureaplasmas were detected by quantitative PCR assays. All BV associated bacteria, except Megasphaera-like type 1, were strongly positively correlated with U. urealyticum p<0.005 and even stronger with the combined U. urealyticum and U. parvum load (p<0.0005) suggesting that ureaplasma induced elevated pH may stimulate the growth of BV associated bacteria. No statistically significant differences were found between IU cases and controls in the prevalence or load of BV associated bacteria or ureaplasmas. In multiple logistic regression, Megasphaera-like type 1 was associated with IU (p = 0.03), but most positive FVU samples contained very few bacteria and the finding may not be clinically relevant.

The role of adhesive and cytokine signaling systems in the pathogenesis of persistent post-eradication urethritis in men, induced by c. trachomatis, u. urealyticum, m. genitalium

The purpose of the study was to investigate the role of soluble intercellular adhesion molecules (ICAM-1, VCAM) in the pathogenesis of persistent non-gonococcal urethritis in men induced by C.trachomatis, U.urealyticum, M. genitalium and to determine their possible association with the content of cytokines in urethral cytokines (IL -6, IL-8). Conclusions: Cytokines with chemokine activity (IL-6, IL-8) and soluble intercellular adhesion molecules (ICAM-1, VCAM) are key factors in the pathogenesis of persistent post-eradication urethritis, which is confirmed by statistically significant differences in the median concentrations of these mediators between patients with persistence Symptoms and clinical cure. Cytokines (IL-6, IL-8) and adhesive molecules (ICAM-1, VCAM) have synergistic effects that promote the recruitment and deposition of immunocompetent cells, as indicated by the presence of a correlation between the concentrations of these mediators. Further studies should be aimed at establishing mechanisms for the development of specific symptoms and ways to correct them.

1491. Mycoplasma genitalium: A Concordance Study in Heterosexual Partnerships at Risk for Chlamydial Infection

Background Mycoplasma genitalium (MG) causes symptomatic nonchlamydial, nongonococcal urethritis in men, and cervicitis, pelvic inflammatory disease and infertility in women. We aimed to determine: prevalence and concordance of MG infection within heterosexual partnerships; MG detection by sample site in infected subjects; symptom association with MG infection; frequency of co-infection with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV); and risk factors associated with MG infection and concordance.MethodsData from two partnership studies were combined; both enrolled sexually active heterosexual couples between the ages of 14–24 years who were at high risk for CT, between April 10, 2000 and September 29, 2003 at a sexually transmitted infection (STI) clinic in Indianapolis, IN. MG was detected by nucleic acid amplification from specimens stored at −70°C for up to 48 months. MG was sought in urine and urethra in men and urine, vagina, and cervix in women. Symptoms evaluated were dysuria, discharge in men and discharge, dysuria, abdominal pain in women. Symptom association with MG infection was analyzed by Chi-square test and logistic regression was used for associations of demographic, behavioral and biologic factors with MG concordance.ResultsMicrobiologic data were available from 200 men and 217 women, and demographic information from 188 men and 201 women in partnerships. 43/217 dyads contained an individual with MG infection, and both individuals were infected in 11/43 (26%) partnerships (concordant). In men and women MG detection was highest in urine (10%, 9%) specimens. Prevalence of MG was 14% in women and10% in men. Most infected men (79%) and women (62%) were African American. Mean age at first sex was 14 years for both genders. CT was the most frequent co-infection in both MG infected men (32%) and women (52%). MG infection without co-infection was associated with penile discharge in men (57%) P = 0.18. No symptoms in women were indicative of MG infection, and no demographic, behavioral or biologic factors were statistically associated with MG concordance.ConclusionThe prevalence of MG was substantial. Concordance in partnerships was 26%, less than observed with CT (~70%) in this study. Our study is limited due to small numbers of subjects with MG infection.Disclosures All authors: No reported disclosures.

Mycoplasma genitalium: Accurate Diagnosis Is Necessary for Adequate Treatment.

Mycoplasma genitalium is very difficult to grow in culture but has been more able to be studied for disease associations since the advent of research molecular amplification assays. Polymerase chain reaction (PCR) and other molecular assays have demonstrated an association with adverse disease outcomes, such as urethritis or nongonococcal urethritis in men and adverse reproductive sequelae in women-for example, cervicitis, endometritis, and pelvic inflammatory disease (PID), including an association with risk for human immunodeficiency virus. The lack of commercially available diagnostic assays has limited widespread routine testing. Increasing reports of high rates of resistance to azithromycin detected in research studies have heightened the need available commercial diagnostic assays as well as standardized methods for detecting resistance markers. This review covers available molecular methods for the diagnosis of M. genitalium and assays to predict the antibiotic susceptibility to azithromycin. A PubMed (US National Library of Medicine and National Institutes of Health) search was conducted for literature published between 2000 and 2016, using the search terms Mycoplasma genitalium, M. genitalium, diagnosis, and detection. Early PCR diagnostic tests focused on the MPa adhesion gene and the 16S ribosomal RNA gene. Subsequently, a transcription-mediated amplification assay targeting ribosomes was developed and widely used to study the epidemiology of M. genitalium. Newer methods have proliferated and include quantitative PCR for organism load, AmpliSens PCR, PCR for the pdhD gene, a PCR-based microarray for multiple sexually transmitted infections, and multiplex PCRs. None yet are cleared by the Food and Drug Administration in the United States, although several assays are CE marked in Europe. As well, many research assays, including PCR, gene sequencing, and melt curve analysis, have been developed to detect the 23S ribosomal RNA gene mutations that confer resistance to azithromycin. One recently developed assay can test for both M. genitalium and azithromycin resistance mutations at the same time. It is recommended that more commercial assays to both diagnose this organism and guide treatment choices should be developed and made available through regulatory approval. Research is needed to establish the cost-effectiveness of routine M. genitalium testing in symptomatic patients and screening in all individuals at high risk of acquiring and transmitting sexually transmitted infections.

Meatal Swabs Contain Less Cellular Material and Are Associated with a Decrease in Gram Stain Smear Quality Compared to Urethral Swabs in Men

Urethral swabs are the samples of choice for point-of-care Gram stain testing to diagnose Neisseria gonorrhoeae infection and nongonococcal urethritis (NGU) in men. As an alternative to urethral swabs, meatal swabs have been recommended for the collection of urethral discharge to diagnose N. gonorrhoeae and Chlamydia trachomatis infection in certain populations by nucleic acid amplification testing (NAAT), as they involve a less invasive collection method. However, as meatal swabs could be sampling a reduced surface area and result in fewer collected epithelial cells compared to urethral swabs, the adequacy of meatal swab specimens to collect sufficient cellular material for Gram stain testing remains unknown. We enrolled 66 men who underwent either urethral or meatal swabbing and compared the cellular content and Gram stain failure rate. We measured the difference in swab cellular content using the Cepheid Xpert CT/NG sample adequacy control crossing threshold (SACCT) and determined the failure rate of Gram stain smears (GSS) due to insufficient cellular material. In the absence of discharge, meatal smears were associated with a significant reduction in cellular content (P = 0.0118), which corresponded with a GSS failure rate significantly higher than that for urethral swabs (45% versus 3%, respectively; P < 0.0001). When discharge was present, there was no difference among results from urethral and meatal swabs. Therefore, if GSS testing is being considered for point-of-care diagnosis of N. gonorrhoeae infection or NGU in men, meatal swabs should be avoided in the absence of a visible discharge.

Background review for the 2016 European guideline on Mycoplasma genitalium infections.

Mycoplasma genitalium is a cause of 10-35% of non-chlamydial non-gonococcal urethritis in men and in women, and is associated with cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium occurs through direct mucosal contact. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. In men, urethritis, dysuria and discharge predominates. Asymptomatic infections are frequent. In this review, we present the evidence base for the recommendations in the 2016 European guideline on M. genitalium infections and describe indications for testing, recommended diagnostic methods, treatment and patient management. The guideline was prepared on behalf of the European branch of The International Union against Sexually Transmitted Infections; the European Academy of Dermatology and Venereology; the European Dermatology Forum; the European Society of Clinical Microbiology and Infectious Diseases; the Union of European Medical Specialists. The European Centre for Disease Prevention and Control and the European Office of the World Health Organisation also contributed to their development.

2016 European guideline on Mycoplasma genitalium infections.

Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium occurs through direct mucosal contact. Asymptomatic infections are frequent. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. In men, urethritis, dysuria and discharge predominates. Besides symptoms, indication for laboratory test is a high-risk sexual behaviour. Diagnosis is achievable only through nucleic acid amplification testing (NAAT). If available, NAAT diagnosis should be followed with an assay for macrolide resistance. Therapy for M. genitalium is indicated if M. genitalium is detected or on an epidemiological basis. Doxycycline has a low cure rate of 30-40%, but does not increase resistance. Azithromycin has a cure rate of 85-95% in macrolide susceptible infections. An extended course appears to have a higher cure rate. An increasing prevalence of macrolide resistance, most likely due to widespread use of azithromycin 1 g single dose without test of cure, is drastically decreasing the cure rate. Moxifloxacin can be used as second-line therapy, but resistance is increasing. Uncomplicated M. genitalium infection should be treated with azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral), or josamycin 500 mg three times daily for 10 days (oral). Second line treatment and treatment for uncomplicated macrolide resistant M. genitalium infection is moxifloxacin 400 mg od for 7-10 days (oral). For third line treatment of persistent M. genitalium infection after azithromycin and moxifloxacin doxycycline 100 mg two times daily for 14 days can be tried and may cure 30%. Pristinamycin 1 g four times daily for 10 days (oral) has a cure rate of app. 90%. Complicated M. genitalium infection (PID, epididymitis) is treated with moxifloxacin 400 mg od for 14 days.

2016 European guideline on the management of non-gonococcal urethritis.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

Mycoplasma genitalium: An Overlooked Sexually Transmitted Pathogen in Women?

Mycoplasma genitalium is a facultative anaerobic organism and a recognized cause of nongonococcal urethritis in men. In women, M. genitalium has been associated with cervicitis, endometritis, pelvic inflammatory disease (PID), infertility, susceptibility to human immunodeficiency virus (HIV), and adverse birth outcomes, indicating a consistent relationship with female genital tract pathology. The global prevalence of M. genitalium among symptomatic and asymptomatic sexually active women ranges between 1 and 6.4%. M. genitalium may play a role in pathogenesis as an independent sexually transmitted pathogen or by facilitating coinfection with another pathogen. The long-term reproductive consequences of M. genitalium infection in asymptomatic individuals need to be investigated further. Though screening for this pathogen is not currently recommended, it should be considered in high-risk populations. Recent guidelines from the Centers for Disease Control regarding first-line treatment for PID do not cover M. genitalium but recommend considering treatment in patients without improvement on standard PID regimens. Prospective studies on the prevalence, pathophysiology, and long-term reproductive consequences of M. genitalium infection in the general population are needed to determine if screening protocols are necessary. New treatment regimens need to be investigated due to increasing drug resistance.

Efficacy of Antimicrobial Therapy for Mycoplasma genitalium Infections.

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

The Efficacy of Azithromycin for the Treatment of Genital Mycoplasma genitalium: A Systematic Review and Meta-analysis.

Mycoplasma genitalium (MG) is associated with nongonococcal urethritis in men and cervicitis in women. Current guidelines recommend treatment with 1 gram of azithromycin; however, treatment failure has increasingly been reported. This meta-analysis estimates treatment efficacy following treatment with 1 gram of azithromycin. Electronic databases were searched for articles published to the end of February 2015 using the following search terms: (Mycoplasma genitalium) AND (azithromycin OR zithromax OR [treatment efficacy]). Studies were included if they were English language, had participants aged ≥12 years diagnosed with urogenital MG, and had microbial cure measured within 12 months of treatment. Treatment efficacy was measured as microbial cure at last follow-up after treatment. A total of 21 studies, including 1490 participants, fulfilled the inclusion criteria. Most studies were observational, with only 5 controlled trials identified. The random-effects pooled microbial cure was 77.2% (95% confidence interval [CI], 71.1%-83.4%; I(2) = 80.8%, P < .01). For the 12 studies conducted prior to 2009, pooled microbial cure was 85.3% (CI, 82.3%-88.3%; I(2) = 19.7%, P = .25); for the 9 studies conducted since the beginning of 2009, pooled microbial cure was 67.0% (CI, 57.0%-76.9%; I(2) = 80.9%, P < .01). The efficacy of a single dose of 1 gram of azithromycin for the treatment of urogenital MG has decreased to approach 60%. Even though most of the available evidence is based on observational studies that have considerable variability in sample size and timing of microbial cure, this low efficacy is of considerable concern. It is vital that new treatment options for MG are investigated.

2015 UK National Guideline on the management of non-gonococcal urethritis.

We present the updated British Association for Sexual Health and HIV guideline for the management of non-gonococcal urethritis in men. This document includes a review of the current literature on its aetiology, diagnosis and management. In particular it highlights the emerging evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium and that neither azithromycin 1 g nor doxycycline 100 mg twice daily for seven days achieves a cure rate of >90% for this micro-organism. Evidence-based diagnostic and management strategies for men presenting with symptoms suggestive of urethritis, those confirmed to have non-gonococcal urethritis and those with persistent symptoms following first-line treatment are detailed.

Trichomonas vaginalis infection: How significant is it in men presenting with recurrent or persistent symptoms of urethritis?

Persistent or recurrent non-gonococcal urethritis has been reported to affect up to 10-20% of men attending sexual health clinics. An audit was undertaken to review the management of persistent or recurrent non-gonococcal urethritis in men presenting at Whittall Street Clinic, Birmingham, UK. Detection of Trichomonas vaginalis infection was with the newly-introduced nucleic acid amplification test. A total of 43 (8%) of 533 men treated for urethritis re-attended within three months with persistent or recurrent symptoms. Chlamydia trachomatis infection was identified in 13/40 (33%), T. vaginalis in 1/27 (4%) and Mycoplasma genitalium in 6/12 (50%). These findings suggest that the prevalence of T. vaginalis infection remains low in our clinic population and may not contribute significantly to persistent or recurrent non-gonococcal urethritis.

Reactive arthritis associated with Mycoplasma genitalium urethritis

Mycoplasma genitalium is an important cause of sexually transmitted infections that is gaining recognition and is an independent cause of acute and chronic nongonococcal urethritis in men. M. genitalium has been implicated as a possible causative factor in reactive arthritis. We report a case of reactive arthritis complicating M. genitalium urethritis in an HLA-B27–positive patient.