Mycoplasma genitalium: Key Information for the Primary Care Clinician.

Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, which appears to be a cause of urethritis and cervicitis and has been associated with pelvic inflammatory disease (PID), epididymitis, proctitis, infertility, complications during pregnancy, and human immunodeficiency virus (HIV) transmission. Three Food and Drug Administration (FDA) approved tests are available. Testing should be focused to avoid inappropriate antibiotic use. The Center of Disease Control and Prevention (CDC) guidelines recommend testing for persistent male urethritis, cervicitis, and proctitis and state that testing should be considered in cases of PID. Testing is also recommended for sexual contacts of patients with MG. Testing is not recommended in asymptomatic patients, including pregnant patients, who do not have a history of MG exposure. Although resistance-guided therapy is recommended, there are currently no FDA approved tests for MG macrolide resistance, and tests are not widely available in the United States. The CDC recommends 2-step treatment with doxycycline followed by azithromycin or moxifloxacin. Moxifloxacin is recommended if resistance testing is unavailable or testing demonstrates macrolide resistance..

Incidence and risk factors of gonococcal urethritis reinfection among Thai male patients in a multicenter, retrospective cohort study.

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.

Mycoplasma genitalium coinfection in men with symptomatic gonococcal urethritis.

OBJECTIVES: International guidelines recommend Mycoplasma genitalium testing, preferably using an assay to detect macrolide resistance-associated mutations, for men presenting with non-gonococcal urethritis, but there is no specific guidance on such testing for men with gonococcal urethritis. METHODS: This study aimed to estimate the proportion of men with gonococcal urethritis who have coinfection with M. genitalium through a retrospective analysis of cases of symptomatic urethral gonorrhoea at Western Sydney Sexual Health Centre in 2017 and 2018. RESULTS: Fourteen of 184 (7.6%, 95% CI 3.7 to 11.5) men with gonococcal urethritis had M. genitalium detected in the urine at the time of presentation. No demographic or behavioural factors predicted M. genitalium coinfection. Coinfection with urethral Chlamydia trachomatis was detected in 29 of 184 (15.8%, 95% CI 10.5 to 21.1). All five men with macrolide-resistant M. genitalium detected returned for treatment with moxifloxacin at a median of 8 days (range 5-16 days) after presentation and treatment of gonorrhoea; three of five were documented to remain symptomatic at this visit. CONCLUSION: Although M. genitalium coinfection is less common than chlamydia among men with symptomatic gonococcal urethritis, M. genitalium testing, using an assay to detect macrolide resistance, will potentially reduce symptom duration particularly for men with macrolide-resistant infections, but may not be justifiable on cost-benefit analysis.

Male urethritis. A review of the ideal diagnostic method. / Uretritis masculina. Una revisión del método ideal de diagnóstico.

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.

Onychocryptosis and asymptomatic external urethritis as complications of oral isotretinoin therapy.

This case report presents a patient who, while undergoing oral isotretinoin therapy for acne vulgaris, developed onychocryptosis and asymptomatic external urethritis. These uncommon adverse events are not well-documented in medical literature. While his urethritis spontaneously resolved, his onychocryptosis symptoms necessitated surgical intervention. This report illustrates both cosmetic and functional adverse effects of isotretinoin and provides insight into the progression of these reactions over time.

The Role of Ureaplasma spp. in the Development of Nongonococcal Urethritis and Infertility among Men.

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

Histopathology of Anterior Urethral Strictures: Toward a Better Understanding of Stricture Pathophysiology.

PURPOSE: Histopathology can provide insights into disease mechanisms but to date it has been poorly described for urethral stricture. The purpose of this study was to comprehensively describe histopathological findings of stricture specimens obtained at the time of anterior urethroplasty. MATERIALS AND METHODS: All pathological specimens of men who underwent anterior urethroplasty of urethral stricture disease from 2010 to 2017 at a single institution were rereviewed by a single blinded pathologist directed to rule out lichen sclerosus and then describe inflammatory cell type and severity when present. Cohorts comprising strictures with no inflammation, minimal to mild inflammation or moderate to severe inflammation were developed and stricture, patient and surgical outcome characteristics were compared. RESULTS: Histopathology slides from 100 anterior urethroplasty cases were reviewed. Two or more lichen sclerosus characteristics were present in 21% of specimens and 44% of specimens showed chronic inflammation, which was minimal in 20%, mild in 39%, moderate in 39% and severe in 2%. Lymphocytes in 86% of specimens and plasma cells in 12% were the predominant cell types. Patients with inflammatory stricture reported worse overall health. Inflammation was largely absent from isolated bulbomembranous strictures (9%) and more common in lichen sclerosus strictures (100%). The 11% overall failure rate was not affected by the presence (7%) or absence (14%) of inflammation. CONCLUSIONS: Chronic inflammation is prevalent in a significant percent of urethral stricture disease specimens. Associations with worse overall health suggest systemic mediators. Absent inflammation in bulbomembranous strictures suggests a unique pathophysiology in this region. The presence of inflammation did not affect surgical outcomes at mid-term followup.

Specific characteristics of urethral strictures in a developing country (Brazil).

PURPOSE: Evaluate the main etiologies and clinical characteristics of male urethral stricture disease (USD) in Brazil. METHODS: This multicentric study was performed using retrospective data collected from six Brazilian referral centers of urethral reconstruction. The database comprised data from 899 patients with USD who had undergone surgical treatment from 2008 to 2018. Age, stricture site and primary stricture etiology were identified for each patient. RESULTS: The mean age was 52.13 ± 16.9 years. The most common etiology was iatrogenic (43.4%), followed by idiopathic (21.7%), trauma (21.5%) and inflammatory (13.7%). Of the iatrogenic causes, 59% were secondary to urethral instrumentation (60% by urethral catheterization and 40% by transurethral procedures), 24.8% by other procedures (prostatectomy, radiotherapy, postectomy) and 16.2% by failed hypospadia repairs. Pelvic fracture urethral distraction injuries were responsible for most of the trauma-related strictures (62.7%). When stratified by age, the most common stricture etiology was trauma in the 0-39 years old group (42.8%), idiopathic in the 40-59 years old group (32.4%) and iatrogenic in patients over 60 years old (68%). In regard to the stricture site, 80% presented with an anterior urethral stricture and 20% with a posterior stenosis. In the anterior stenosis group, the most common stricture site was bulbar (39.5%). CONCLUSION: In Brazil, as in many developed countries, the most common cause of urethral stricture diseases is iatrogenic, especially urethral catheterization. These findings emphasize the need of a careful urethral manipulation and a better training of healthcare professionals. Trauma is still responsible for a great proportion of strictures and inflammatory etiologies are now less frequently observed.

Microscopic examination of Gram-stained smears for anogenital gonorrhoea in men who have sex with men is cost-effective: evidence from a modelling study.

OBJECTIVE: To assess the cost-effectiveness of three testing strategies with or without light microscopic Gram-stained smear (GSS) evaluation for the detection of anogenital gonorrhoea among men who have sex with men (MSM) at the Amsterdam STI clinic using a healthcare payer perspective. METHODS: Three testing strategies for MSM were compared: (1) GSS in symptomatic MSM only (currently practised strategy), (2) no GSS and (3) GSS in symptomatic and asymptomatic MSM. The three testing protocols include testing with nucleic acid amplification test to verify the GSS results in (1) and (3), or as the only test in (2). A transmission model was employed to calculate the influence of the testing strategies on the prevalence of anogenital gonorrhoea over 10 years. An economic model combined cost data on medical consultations, tests and treatment and utility data to estimate the number of epididymitis cases and quality-adjusted life years (QALY) associated with gonorrhoea. Incremental cost-effectiveness ratios (ICERs) for the testing scenarios were estimated. Uncertainty and sensitivity analyses were performed. RESULTS: No GSS testing compared with GSS in symptomatic MSM only (current strategy) resulted in nine extra epididymitis cases (95% uncertainty interval (UI): 2-22), 72 QALYs lost (95% UI: 59-187) and €7300 additional costs (95% UI: -€185 000 (i.e.cost-saving) to €407 000) over 10 years. GSS testing in both symptomatic and asymptomatic MSM compared with GSS in symptomatic MSM only resulted in one prevented epididymitis case (95% UI: 0-2), 1.1 QALY gained (95% UI: 0.1-3.3), €148 000 additional costs (95% UI: €86 000 to-€217 000) and an ICER of €177 000 (95% UI: €67 000-to €705 000) per QALY gained over 10 years. The results were robust in sensitivity analyses. CONCLUSIONS: GSS for symptomatic MSM only is cost-effective compared with no GSS for MSM and with GSS for both symptomatic and asymptomatic MSM.

Antibiotic resistance in Neisseria gonorrhoea and treatment outcomes of gonococcal urethritis suspected patients in two large hospitals in Bhutan, 2015.

INTRODUCTION: Gonorrhea is a major sexually transmitted infection (STI) globally with increasing trends. Despite limited data, gonorrhea remains an important public health problem in Bhutan. METHODS: A descriptive study was carried out in two Bhutanese hospitals; Jigme Dorji Wangchuck National Referral Hospital and Phuentsholing General Hospital in 2015. Patients suspected of gonococcal urethritis were sampled, treated and followed up at two weeks. Gonococcal isolates were identified and tested for antibiotic susceptibility by the Calibrated Dichotomous Sensitivity Test (CDS) method. RESULTS: Of the 524 patients, 2.3% (12) were females. Most (46.6%) patients belonged to the 26-35 years age group. About 58% were lost to follow up; 62% (277) of males and all (12) females. N. gonorrhoea was positive in 76% (398) of microscopy and 73.1% (383) by culture. Resistance against ciprofloxacin, penicillin, tetracycline and nalidixic acid were 85.1%, 99.2%, 84.8% and 99.7% respectively. Nearly all the isolates were sensitive to cefpodoxime, ceftriaxone and azithromycin. Sixty-seven percent (350) were treated with injection ceftriaxone alone, 32% (169) with ceftriaxone and oral doxycycline and 1% (5) with ceftriaxone, doxycycline and metronidazole. Probable treatment failure was seen only in one patient (0.5%). CONCLUSIONS: Gonococcal resistance to currently used antibiotics was low and there was a high clinical cure rate. Compliance to treatment guidelines need reinforcement addressing antibiotic regimen, tracing sexual partners and addressing the social stigma. National STI programs should be more women-friendly for effective management, prevention and control of STIs. Laboratories must adopt more reliable susceptibility testing methods, the Minimum Inhibition Concentration method.

Corymbiform syphilis associated with three other sexually transmitted infections.

Secondary syphilis can have different clinical presentations, with corymbiform rash as its rarest manifestation. The disease is characterized by a central papule surrounded by smaller ones. We report the case of a man who has sex with man with corymbiform syphilis. The patient was subsequently diagnosed with HIV infection, hepatitis B, non-gonococcal urethritis, as well as infection of the central nervous system by treponema. This case not only illustrates a rare presentation of secondary syphilis, but also demonstrates the importance of further investigation of sexually transmitted infections, particularly among at-risk patients.

Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae alleles.

BACKGROUND: Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015. RESULTS: The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected. CONCLUSIONS: Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the frequency with which it causes urethritis.

Corymbiform syphilis associated with three other sexually transmitted infections

Abstract: Secondary syphilis can have different clinical presentations, with corymbiform rash as its rarest manifestation. The disease is characterized by a central papule surrounded by smaller ones. We report the case of a man who has sex with man with corymbiform syphilis. The patient was subsequently diagnosed with HIV infection, hepatitis B, non-gonococcal urethritis, as well as infection of the central nervous system by treponema. This case not only illustrates a rare presentation of secondary syphilis, but also demonstrates the importance of further investigation of sexually transmitted infections, particularly among at-risk patients.

Auditing the use and assessing the clinical utility of microscopy as a point-of-care test for Neisseria gonorrhoeae in a Sexual Health clinic.

We assessed whether urethral microscopy was performed as per clinic protocol for male clinic attendees reporting contact with Neisseria gonorrhoeae (GC), urethral symptoms or given a diagnosis of epididymo-orchitis (EO) over a 12-month period (9732 patients). Prevalence of gonorrhoea in the contacts, urethral symptoms and EO groups was 50, 12.7 and 1.6%, respectively. Microscopy was performed reliably for contacts (96%), those with discharge/dysuria with evidence of urethritis on examination (98%), but not those with EO (43%). We explored the clinical utility of microscopy as a point-of-care test for identifying urethral GC in each subgroup, using the APTIMA Combo 2 CT/GC nucleic acid amplification test as the comparator (1710 patients). Sensitivity of microscopy for each subgroup was good; there was no statistical difference between subgroup sensitivity using Fisher's exact test. Microscopy is valuable to ensure prompt diagnosis and contact tracing. All GC contacts were treated 'epidemiologically'; however, half of GC contacts did not have GC. Microscopy identified the majority of GC cases, including amongst contacts (71% of heterosexual contacts, 66% of contacts reporting sex with men). We propose that epidemiological treatment for GC contacts should be reconsidered on the grounds of antibiotic stewardship, favouring use of microscopy to guide treatment decisions.

Mycoplasma genitalium: Accurate Diagnosis Is Necessary for Adequate Treatment.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

The Unique Microbiology and Molecular Pathogenesis of Mycoplasma genitalium.

Mycoplasma genitalium is increasingly appreciated as a common cause of sexually transmitted disease syndromes, including urethritis in men and cervicitis, endometritis, pelvic inflammatory disease, and possibly preterm birth, tubal factor infertility, and ectopic pregnancy in women. Despite these disease associations, which parallel those of Chlamydia trachomatis and Neisseria gonorrhoeae, the mechanisms by which this pathogen elicits inflammation, causes cellular damage, and persists in its only natural host (humans) are unique and are not fully understood. The purpose of this review is to briefly provide a historical background on the discovery, microbiology, and recognition of M. genitalium as a pathogen, and then summarize the recent advances in our understanding of the molecular biology and pathogenesis of this unique urogenital organism. Collectively, the basic scientific discussions herein should provide a framework for understanding the clinical and epidemiological outcomes described in the accompanying articles in this supplemental issue.

Neisseria gonorrhoeae DNA bacterial load in men with symptomatic and asymptomatic gonococcal urethritis.

OBJECTIVE: Previous studies have quantified bacterial loads of Neisseria gonorrhoeae in the pharynx and rectum of men but not the urethra. We quantified the bacterial load of N. gonorrhoeae in men with symptomatic and asymptomatic urethral gonorrhoea infections. METHODS: Consecutive men diagnosed with urethral gonorrhoea by Aptima Combo 2 testing of urine at the Melbourne Sexual Health Centre between March and July 2016 were eligible for the study: symptomatic men with purulent urethral discharge and asymptomatic men with no urethral symptoms. The gonococcal bacterial load in both groups was measured by urethral swab using a standardised collection method and real-time quantitative PCR targeting the opa gene. RESULTS: Twenty men were recruited into the study: 16 had purulent urethral discharge and 4 had asymptomatic urethral gonorrhoea. The median gonococcal bacterial load was significantly higher among symptomatic men (3.7×106 copies per swab, IQR 2.5×106-4.7×106) compared with asymptomatic men (2.0×105 copies per swab, IQR 2.7×104-4.5×105) (p=0.002). CONCLUSIONS: Gonococcal loads in men with urethral discharge were higher than loads seen with asymptomatic urethral gonorrhoea and loads seen in asymptomatic pharyngeal and rectal gonorrhoea infections in previous studies.

[Impact of Mycoplasma and Chlamydia infections on male reproduction].

Infertility can be attributed to reproductive tract infections (RTI), most commonly nongonococcal urethritis, mainly including Mycoplasma and Chlamydia infections, which may directly or indirectly damage spermatozoa and spermatogenic cells. In addition, a series of immune responses caused by such infections are also associated with male infertility. Methods for the clinical detection of these microbial infections are being constantly improved for more specific and precise control over the impact of Mycoplasma and Chlamydia infections on male fertility.