Idiopathic Urethritis Research Articles

A novel therapy for idiopathic urethritis in children: Local steroid injection

Idiopathic urethritis (IU) is difficult to manage and there is no standarized therapy. The technique of local steroid injection (LSI) for the treatment of IU in children and the results of the patients undergoing LSI from 2020 to 2021 in a single center are presented. Seven patients with IU underwent LSI. An internal urethrotomy was also performed in two patients with stricture. Complete resolution of symptoms and signs occurred in six patients. The remaining patient did not achieve total remission but did substantially improve symptoms. LSI seems to be an effective alternative for treatment of IU in children.

Characterization of Virulence-Associated Traits in Mycoplasma penetrans Strains Acting as Likely Etiological Agents of Idiopathic Nongonococcal Urethritis.

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.

The Urethral Microbiota of Men with and without Idiopathic Urethritis.

ABSTRACTNongonococcal 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.

Idiopathic urethritis in children and adolescents: a challange still open

Idiopathic urethritis in children and adolescents: a challange still open

Idiopathic Urethritis in Childhood

Introduction: Idiopathic urethritis (IU) in childhood is a rare disease with very few cases reported so far. Methods: During the past 3 years, the medical records of young boys diagnosed with and treated for IU in our department were retrieved and analyzed. Herein, their clinical course is presented, and a brief review of the literature is performed. Results: Five young male patients (mean age: 8.2 years) presented to the pediatric office with blood spotting of the underwear or urethral discharge, with or without dysuria. All the patients were treated in an outpatient basis and the corresponding clinical courses after a mean follow-up was 15.8 months were favorable. Conclusions: IU is a rare disease with a generally benign clinical course. Treatment must be tailored to symptomatic relief with avoidance of antibiotics. An aggressive diagnostic workup should be reserved to those with persistent symptoms or frequent recurrences.

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...

No Pathogen-Specific Sign or Symptom Predicts the Etiology of Monomicrobial Nongonococcal Urethritis in Men.

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.

Characteristic of urethral microbiota of men with idiopathic urethritis

Aim: to study the urethral microbiota composition in urogenital infections in men and to determine the sensitivity of isolated microorganisms to antibacterial drugs.Materials and Methods. 957 samples of biological material from the urethra of men were examined. The identification of the microorganisms was carried out according to the Bergey's Manual of Systematic Bacteriology. Sensitivity to antibiotics was determined by the disco-diffusion method, using standard disks of industrial production in accordance with the order of the Ministry of Health of Ukraine No. 167 of 05.04.2007. The mathematical processing of the results was performed, using the computer program Origin Pro 7.0.Results of the research. According to the study, the presence of conditionally pathogenic microorganisms was found in 716 people (74.82% of the total number of the surveyed contingent). Of the subjects studied, 1574 strains were isolated, of which the vast majority consisted of bacteria of the intestinal group (43.52%) and staphylococci (32.46%). The incidence of streptococci was 18.61%, corynebacteria - 3.81%, pseudomonads - 1.14%, candida - 0.44%. When studying the species composition of urethral microbiota, the presence of monoinfection was found in 267 people, in the other 449 persons different associations of representatives of conditionally pathogenic microbiota were detected. The analysis of the level of sensitivity of the studied strains to antibiotics showed that the isolated staphylococci showed the highest sensitivity to ampicillin / sulbactam (81.60% sensitive strains), most cephalosporins (79,26 ± 4,49%), carbapenems (93,35 ± 1,38 %), vancomycin (100%), rifampicin (92.56%), most fluoroquinolones (82.68 ± 3.31%) and linezolid (98.63). Whereas the highest number of susceptible strains of bacteria of the intestinal group was determined for carbapenems (89.64 ± 2.68%) and Co-trimoxazole (82.19%).Conclusions. Isolated bacterial strains of the intestinal group and staphylococci are most commonly found in association with other microorganisms. The analysis of the level of antibiotic sensitivity indicates that staphylococci showed the highest sensitivity to ampicillin / sulbactam, most cephalosporins, carbapenems, vancomycin, rifampicin, most aminoglycosides and linezolid. Whereas the highest number of susceptible strains of bacteria of the intestinal group was determined for carbapenems and Co-trimoxazole. Which makes the use of these antibiotics appropriate for the treatment of diseases of the men's genitourinary system

Identification of Microbes Associated with the Urethra during Health and Inflammation

The number of cases of urethritis, or inflammation of the male urethra, in the US has been estimated to be 2.8 million each year in the United States.1 It is the most common reason young men seek primary care and this syndrome is associated with acute proctitis, epididymitis, and orchitis.2 Approximately half of the cases are idiopathic, meaning that a causative agent cannot be identified. The goal of my project is to identify and characterize novel microorganisms that may be associated with male idiopathic urethritis. We used a variety of approaches to cultivate microorganisms from archived urethral swabs collected from men with idiopathic urethritis and healthy controls. We defined the phylogeny of the isolates using 16S rRNA sequencing to identify organisms that are not presently represented in microbial databases. Currently, we are scaling up a number of novel taxa we identified for genome sequencing. By adding these new genome sequencing to the existing databases we will be able to assign a higher proportion of reads from corresponding metagenomic sequence data and achieve a more complete survey of the male urethral microbiota in health and urethritis. This will provide crucial information which may permit us to identify urethritis associated organisms, develop new molecular diagnostics for these organisms, and discern if how these organisms are sexually transmitted 

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.

Preliminary Experience with Instillation of Triamcinolone Acetonide into the Urethra for Idiopathic Urethritis: A Prospective Pilot Study.

Idiopathic bulbar urethritis (IBU) is characterized by hematuria ± dysuria without infection. Symptoms result from inflammation of the bulbar urethra, distal to external sphincter. IBU is difficult to manage and there is no recommended therapy. To determine whether instillation of triamcinolone acetonide is a useful treatment of IBU and its associated complications. Data were prospectively collected, for 22 months, on 14 consecutive patients presenting with terminal hematuria or blood spotting ± dysuria to a pediatric urology unit. Median age was 12 years (range: 10-15). Mean symptom duration was 13 months (range: 8-24). Normal baseline laboratory blood tests, urine cultures, and ultrasound assessments were seen in all; therefore, none were excluded on the basis of a known pathology. Follow-up telephone interviews, to assess symptom persistence and side effects, were performed at 6 weeks postintervention. The mean follow-up period was 15 months (range: 4-20). Visual confirmation of IBU was obtained cystoscopically and 40 mg of triamcinolone was instilled to the inflamed area under direct vision using an open-ended ureteral catheter. Symptoms resolution was the primary outcome. Repeat cystoscopic assessment ± triamcinolone instillation was recorded, as was the occurrence of complications. Seven patients (50%) required at least one further treatment. Overall complete or partial resolution was reported in 12/14 patients (85.7%). No side effects were reported. This small prospective series demonstrates that intraurethral instillation of triamcinolone seems to be a promising treatment option to alleviate inflammatory symptoms in majority of cases of idiopathic urethritis. Patient Summary: Fourteen boys with inflammation of the urethra, with no identifiable cause, were treated by topically triamcinolone, directly to the inflamed area. We demonstrate an 85.7% complete/partial resolution of symptoms with no side effects seen.

Management strategies for idiopathic urethritis

Williams and Mikhael (1971) described idiopathic urethritis (IU) as a self-limiting condition that affects boys aged 5-15 years, with symptoms of urethrorrhagia, dysuria and haematuria. However, a proportion of boys will remain symptomatic for several years, and may develop urethral stricture (Poch et al., 2007; Palagiri et al., 2003). There is no universally effective treatment for IU, although various strategies have been employed. To review the presentation and long-term outcomes of boys with IU, and present the efficacy of management strategies that have been utilised. A retrospective review was performed of all boys with IU. It was based on clinical and cystoscopic findings for presentation, medical history, management and clinical progress. Fifty-four boys were included, with a median age of 11 years (range 5-15 years) at presentation. The median duration of symptoms was 18 months (range 2-132 months). The median follow-up was 18.5 months (range 1-120 months). Seven (13.0%) boys had early urethral stricture at initial cystourethroscopy, and one (1.9%) developed stricture during follow-up. Thirty-six boys (66.7%) had previous circumcision and four (7.4%) had meatal stenosis. Eight (14.8%) had previous hypospadias repair. Whilst 50% of boys with IU do not require any specific treatment, those with severe/unremitting symptoms may benefit from a trial of urethral steroids or short-term urethral catheterisation. The mechanisms of benefit from these modalities are unclear and they require further evaluation.

Mycoplasma genitalium – The missing pathogen?

M. genitalium has become an established cause of sexually transmitted urethritis and cervicitis, and there is increasing evidence that it may cause upper genital tract disease in women. Detection by nucleic acid amplification tests is currently the only diagnostic method available, but no FDA approved assays are currently available, and the CE marked tests suffer from limited clinical evaluation. In most settings, M. genitalium infections explain 15-25% of symptomatic non-gonococcal urethritis, but as diagnosis of the infection is not routinely carried out, treatment is usually syndromic. A few randomized trials have evaluated treatment of M. genitalium, and have compared only doxycycline 200 mg daily for 7 days with a 1 g single dose of azithromycin. Together with results from open trials, it is obvious that doxycycline is inefficient in eradicating M. genitalium, showing eradication rates around 35%. The eradication rate after azithromycin 1 g single dose is significantly better, but differs greatly between studies. Thus, older studies appear to have higher eradication rates than the most recent one, where no significant difference between azithromycin and doxycycline could be demonstrated. Furthermore, a lower eradication rate is reported in studies from centres where azithromycin has been used as the primary treatment for chlamydial and idiopathic urethritis and cervicitis, suggesting that selection for macrolide resistance may be rapid and widespread. At present, the only second line antibiotic that has been shown to have a high activity against macrolide resistant M. genitalium is moxifloxacin. However, this drug is significantly more expensive and has a less favourable safety profile than macrolides, and multidrug resistant infections have emerged, primarily in patients with contact to South East Asia. Consequently, there is an urgent need for clinical trials with possible alternative drugs. Such trials should preferably also address the treatment efficacy in chlamydial and idiopathic urethritis and cervicitis as a single treatment covering these conditions would be advantageous.

Steroid Instillation for Idiopathic Urethritis in Children: An 8-Year experience

Idiopathic urethritis (IU) in children is of unknown etiology and treatment options are limited. We aim to report our experience with steroid instillation in IU in children. Retrospective data collection of all male children diagnosed with IU over a period of 8 years. Patients with balanitis xerotica obliterans (BXO) and positive urine culture at presentation were excluded from the study. Data were collected on patient demographics, laboratory and radiological investigations, cystoscopy findings, management, and outcomes. A total of 16 male children were diagnosed with IU. The mean age was 11.6 (7-16) years. Presenting symptoms included dysuria in 10; frank hematuria in 7; loin pain in 5; and scrotal pain in 2 patients. Serum C-reactive protein and full blood count was tested in 13 patients and was within normal limits in all of them. Endoscopy findings included posterior urethritis in 12, anterior urethritis in 2, and urethral stricture with inflammation in 2 patients. Ten patients required more than one episode of steroid instillation. Mean follow-up was 19.4 (1-74) months. Complete resolution of symptoms and signs occurred in 15 (93.6%) patients and improvement of symptoms and signs noted with ongoing treatment in 1 (6.4%) patient. IU in children can be successfully managed with steroid instillation. In our series, 93.6% of children had complete resolution of symptoms.

Idiopathic urethritis in children: Classification and treatment with steroids.

Background:Idiopathic urethritis [IU] in children is of unknown etiology and treatment options are limited. We propose a classification for IU based on cystourethroscopy findings and symptoms (Grade 1 – 4) and report our experience with use of topical and oral steroids in IU.Materials and Methods:Retrospective data collection of all male children (0-16 years) diagnosed with IU over a period of 8 years between 2005 and 2012 at our institution. Data was collected on patient demographics, laboratory and radiological investigations, cystourethroscopy findings, management and outcomes. Results: A total of 19 male children were diagnosed with IU. The median age of the patients was 13(7-16) years. Presenting symptoms included dysuria in 12; hematuria in 9; loin pain in 6; and scrotal pain in 2 patients. Both patients with scrotal pain had previous left scrotal exploration that revealed epididymitis. Serum C-reactive protein and Full blood count was tested in 15 patients and was within normal limits in all of them. Cystourethroscopy revealed urethritis of grade-I in 2; grade-II in 11; and grade-III in 3 patients. There were 3 patients with systemic symptoms from extra-urethral extension of inflammation (grade-IV). Mean follow up was 18.9(1-74) months. All patients had steroid instillation at the time of cystourethroscopy. Three patients with IU grade IV required oral steroids (prednisolone) in view of exacerbation of symptoms and signs despite steroid instillation. Complete resolution of symptoms and signs occurred in 18(94.7%) patients. Significant improvement in symptoms and signs was noted in 1(5.3%) patient who is still undergoing treatment.Conclusions:IU in male children can be successfully managed with steroid instillation, especially in grade I and II. Grade III, will need steroid instillation but treatment of scarring and stricture will necessitate longer duration of treatment. In children with IU and extra-urethral symptoms (grade IV), oral steroids may be required.

Bacterial Vaginosis–Associated Bacteria in Men

Approximately 45% of nongonococcal urethritis cases have no identified etiology. Novel bacteria recently associated with bacterial vaginosis (BV) in women may be involved. We evaluated the association of idiopathic nongonococcal urethritis and 5 newly described BV-associated bacteria (BVAB). Heterosexual men 16 years or older attending a sexually transmitted disease clinic in Seattle, Washington, from May 2007 to July 2011 and negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum-biovar2 were eligible. Cases had urethral discharge or 5 or more polymorphonuclear leukocytes per high-power field in urethral exudates. Controls had no urethral discharge and less than 5 polymorphonuclear leukocytes per high-power field. Urine was tested for Atopobium spp., BVAB-2, BVAB-3, Megasphaera spp., and Leptotrichia/Sneathia spp. using quantitative taxon-directed polymerase chain reaction. Cases (n = 157) and controls (n = 102) were of similar age, education, and income, and most were white. Leptotrichia/Sneathia spp. was significantly associated with urethritis (24/157 [15.3%] vs. 6/102 [5.9%], P = 0.03). BVAB-2 was more common in cases than in controls (7/157 [4.5%] vs. 1/102 [1.0%], P = 0.15), and BVAB-3 (n = 2) and Megasphaera spp. (n = 1) were only detected in men with urethritis, but these bacteria were found only in men who also had Leptotrichia/Sneathia spp. Atopobium spp. was not associated with urethritis. The quantity of bacteria did not differ between cases and controls. Among treated cases, doxycycline was more effective than azithromycin for clinical cure of men with Leptotrichia/Sneathia spp. (9/10 vs. 7/12, P = 0.16) and BVAB-2 (3/3 vs. 0/3, P = 0.10). Leptotrichia/Sneathia spp. may be urethral pathogens or contribute to a pathogenic microbiota that can also include BVAB-2, BVAB-3, and Megasphaera spp. Doxycycline may be more effective than azithromycin against these newly identified bacteria.

Upper urinary tract inflammation and dilatation secondary to idiopathic urethritis: A plea for steroid treatment

Upper urinary tract inflammation and dilatation secondary to idiopathic urethritis: A plea for steroid treatment

S08.4 Mycoplasma Genitalium : Implications For Disease, Treatment and the Public Health

M. genitalium is an established cause of sexually transmitted urethritis and cervicitis, and may cause upper tract disease in women. Detection by nucleic acid amplification tests is currently the only...

Longterm Follow-Up of Idiopathic Urethritis

Purpose To study clinical features longterm outcomes of peripubertal boys presenting with dysuria haematuria diagnosed endoscopically with idiopathic urethritis. Material and Methods The case notes of all the patients presenting over the last 7yrs with idiopathic urethritis were retrospectively reviewed for age, symptoms, radiological evaluation, cystoscopy findings and outcome. Mean follow up was 3.7y (Range 2-7yrs). Results Ten boys, Mean age 11.5y (Range 5-14yrs) have been identified. Eight boys presented with dysuria/haematuria alone, 2 boys presented with significant obstructive symptoms. All patients were assessed and diagnosed endoscopically. Endoscopic features fell into 2 distinct groups at presentation. (Group A) Bulbar urethral erythematous inflammation with multiple fronding of urethral mucosa(8). (Group B) Major disruption of bulbar urethra with membranous obstruction and severe haemorrhagic inflammation(2). Biopsy showed non specific inflammation or no inflammation. Urine cultures have always been negative. Urinary tract ultrasound has not shown any abnormality Group A. Five boys (62%%) have had complete resolution of symptoms after several years Two (22%) still have intermittent non-obstructive symptoms One has progressed to obstructive symptoms and endoscopic changes after 5 years, necessitating dilatation. Group B. One has eventually developed complete obstruction and eventual urethroplasty. This patient had undergone successful distal Hypospadias repair 11 years previously. The other has ongoing obstructive symptoms 4 years after diagnosis. Conclusions 1. Idiopathic urethritis may be 2 different conditions 2. Patients with Bulbar urethral erythematous inflammation will generally resolve slowly, even after endoscopic examination, but not always. 3. Patients who present with stricture may obstruct completely and require urethroplasty.

Idiopathic urethritis in young men in the United States: prevalence and comparison to infections with known sexually transmitted pathogens.

Urethritis is the most common male reproductive tract disease syndrome; yet 20-50% of diagnosed cases have no defined etiology, and few population-level data exist on the prevalence or etiology of the syndrome. We estimated the prevalence of urethritis among young men in the United States and compared correlates of idiopathic cases to correlates of detected infections with sexually transmitted pathogens. Questionnaire data and urine specimens from 5,447 men aged 18-27 years participating in Wave III of the National Longitudinal Study of Adolescent Health were analyzed. Symptomatic urethritis was defined as self-reported dysuria or urethral discharge in the past 24hours. Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium were identified using nucleic acid amplification tests. Idiopathic urethritis (IU) was defined as urethral symptoms in the absence of these four pathogens. Stratified weighted analyses generated population-based estimates. Urethritis was reported by 1.2% (95% CI=.8-1.6%) of men, of whom 82.4% (61.1-93.3%) had IU. Men with previous STD diagnoses (aOR=9.3 [95% CI=3.0-28.7]), or fewer (1-4) or no lifetime vaginal sex partners (aOR=7.5 [2.9-19.3] and aOR=7.2 [1.9-27.4]), were more likely to have IU compared with men without urethral symptoms or identified pathogens, whereas men of Native American or Asian/Pacific Islander descent (aOR=.04 [.01-.2]) and heavy drinkers (aOR=.08 [.03-.2]) were less likely to have IU. Unlike infection with known pathogens, IU was not associated with black race, Hispanic ethnicity, or age at sexual debut. Urethral symptoms were rarely associated with known pathogens. IU and known pathogens were associated with distinct characteristics.