Urethritis is inflammation of the urethra and is a lower urinary tract infection. The urethra is a fibromuscular tube through which urine exits the body in both males and females, and semen in males. Urethritis has a strong association with sexually transmitted infections (STIs). Urethritis is characterized as gonococcal or nongonococcal infections. Neisseria gonorrhea and Chlamydia trachomatis are the most common causative organisms of STIs.[1] The most common symptom of urethritis is urethral discharge.[2][3]
Inflammation of the urethra is most frequently due to an infectious etiology, with STIs being the most common cause. Sexually transmitted urethritis has two classifications: gonococcal urethritis (GCU) caused by infections with Neisseria gonorrhea or nongonococcal urethritis (NGU).
Other infectious etiologies associated with urethritis include:
Non-infectious etiologies associated with urethritis include:
Urethritis has an incidence of affecting 4 million Americans each year. The incidence of Neisseria gonorrhea is estimated at over 600,000 new cases annually, and the incidence of nongonococcal urethritis is approximately 3 million new cases annually.
One study of 424 men presenting with signs and symptoms of acute urethritis of which 127 (30%) had infections of N. gonorrhea. In the other 297 males with nongonococcal urethritis, the infectious agent in almost half of them was C. trachomatis with 143 (48.1%) infections. In 154 men presenting with non-chlamydial nongonococcal urethritis, the agents detected were: M. genitalium (22.7%), U. urealyticum (19.5%), human adenovirus (16.2%), H. influenzae (14.3%), U. parvum (9.1%), M. hominis (5.8%) , N meningitidis (3.9%), T vaginalis (1.3%), and various forms of herpes simplex virus 1 (7.1%) and 2 (2.6%).[2]
Urethritis is more commonly diagnosed in males.[2] Risk factors include young age, unprotected sexual intercourse, and multiple sexual partners. Neisseria gonorrhea is one of the most common sexually transmitted diseases and the bacterial cause of gonococcal urethritis in males and cervicitis in females.[6]Chlamydia trachomatis is among the most common sexually transmitted diseases. It is the most common cause of nongonococcal urethritis in males and cervicitis in females. Trichomonas vaginalis infections are also very common, however, prevalence is difficult to quantify due to many asymptomatic cases and these infections are not required to be reported to public health departments. Vaginalis is also a common cause of nongonococcal urethritis in Africa.[8]Mycoplasma genitalium is the causative agent in approximately 15-20% of nongonococcal urethritis in men.[3]
For cases of NGU, Chlamydia trachomatis continues to be a primary concern, although Trichomonas vaginalis and Mycoplasma genitalium are increasingly recognized as significant pathogens. Whereas, the less common bacterial infectious agents are Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, and Gardnerella vaginalis.
Urethritis is documented based on any of the following signs or laboratory tests [9][4]:
Urethritis is commonly asymptomatic; if symptomatic, the symptoms vary based on the causative organism.
Symptoms of urethritis may include dysuria, pruritus, burning, and discharge at the urethral meatus. Frank purulent discharge suggests gonorrhea as the causative organism. Dysuria alone is common among chlamydia. If the patient has dysuria with painful genital ulcers, the causative organism is most likely herpes simplex virus.[3]
Neisseria gonorrhea is often associated with copious purulent or mucopurulent urethral discharge in men or can be asymptomatic. In women, urethritis is often associated with cervicitis or may be asymptomatic. If symptoms are present, dysuria is the most common. Other symptoms in women can include frequency and urgency.[2]
Chlamydia trachomatis is most commonly asymptomatic. Symptomatic patients can have dysuria and urethral discharge. Females with urethritis usually also have cervicitis. Female patients may report dysuria, urgency, or frequency. Symptoms of cervicitis include intermenstrual vaginal bleeding, post-coital bleeding, and changes in vaginal discharge. Cervicitis symptoms may be the reported chief complaint of females with urethritis. Males that are symptomatic may complain of mucoid or watery discharge and dysuria. A small number of patients with chlamydial urethritis may develop reactive urethritis triad.
Mycoplasma genitalium infections are commonly asymptomatic, however; symptoms may include dysuria, purulent or mucopurulent urethral discharge, urethral pruritus, balanitis, and posthitis. The urethral discharge is commonly associated with this organism but, is not always evident in contrast to the Neisseria gonorrhea infections. It can cause acute and persistent urethritis in men.[3][6]
Herpes simplex virus usually presents with intense dysuria. On physical examination, a limited amount of discharge can be present and commonly meatitis and balanitis. The majority of patients may not have herpetic lesions present at the time of examination but generally presents shortly after.
Adenovirus commonly presents with intense dysuria instead of urethral irritation which helps differentiates it from other causes of nongonococcal urethritis. Usually transmitted by oral sex with upper respiratory tract symptoms generally during fall and winter months. Patients usually do not report urethral discharge. The genitourinary examination usually shows scant urethral serous discharge as well as meatitis and balanitis. It is important to perform a complete physical examination as associated constitutional symptoms and conjunctivitis assist in the diagnosis.[2][6]
Some data indicate that enteric organisms are causative agents of urethritis from rectal exposure — gram-negative rods from urinary tract infections or anal sex. Haemophilus species, Neisseria meningitides, Moraxella catarrhalis, and Streptococcus pneumonia are pathogens associated with oral sex causing NGU.[6]
Urethritis is clinically suspected when any sexually active patient presents with symptoms consistent with urethritis including pruritus, discharge or dysuria. Urethritis is mostly a clinical diagnosis based on history and physical examination, however; there are some specific diagnostic laboratory tests utilized.[8] Diagnosis is made based on examination showing evidence of mucopurulent or purulent discharge, >2 WBC per oil immersion field from gram stain of a urethral swab, positive leukocyte esterase and/or presence of >10 WBCs per high-power field of the first-void urine. Diagnosis depends on the availability of point-of-care testing. The Gram stain test has been traditionally the gold standard for the diagnosis of urethritis. A new technique (methylene blue/gentian violet [MB/GV] smear) has had reports as an alternative to Gram staining. MB/GV does not require heat fixation and has very similar performance characteristics to Gram stain. Taylor et al. [10] found the sensitivity of both Gram stain and MB/GV to be 97.3% for the detection of gonococcal infection compared with culture. The specificity of Gram stain and MB/GV was 99.6%, and investigation showed 100% correlation between Gram stain and MB/GV for the detection of GC.[6]
Neisseria gonorrhea is diagnosed initially with nucleic acid amplification testing with first-catch urine or urethral swab. Urethral swab Gram stain exhibits gram-negative diplococci bacteria. A urethral culture provides essential information regarding antibiotic resistance. Other diagnostic testing includes microscopy for males, culture, urethral culture, antigen detection, and endocervical or urethral swabs used with genetic probe methods.
Chlamydia trachomatis is diagnosable in females based on urinalysis revealing pyuria with no organisms reported on Gram stain or culture. No organisms are generally seen on Gram stain due to the organism being a small gram-negative obligate intracellular parasitic bacteria. In sexually active young female patients with pyuria and no bacteriuria, there should be a strong suspicion of urethritis caused by chlamydia. The laboratory test of choice is the Nucleic acid amplification test with a first-void urine. Other available tests are urethral culture, vaginal culture, antigen detection, and genetic probes.[6]
Mycoplasma genitalium diagnosis can be difficult, however; the only FDA approved test is nucleic acid amplification tests which in most clinical settings are widely unavailable.
Therapy should be directed based on the offending agent causing the urethritis.
Gonococcal urethritis: the recommended treatment of choice is a single dose of ceftriaxone 250mg intramuscular injection and a single dose of oral 1 gram of azithromycin to cover for coinfection with chlamydia. Neisseria meningitides urethritis is treated the same.
Nongonococcal urethritis: the recommended treatment:
Chlamydia trachomatis: The treatment of choice is a single dose of 1 gram of oral azithromycin or 100mg doxycycline twice a day for seven days. Alternative treatment options are ofloxacin 300mg orally twice daily for seven days or levofloxacin 500mg orally once a day for seven days. If coinfected with gonorrhea treatment with one dose of 250mg ceftriaxone intramuscular injection in addition to 1 gram oral single dose azithromycin. In pregnant females, 1 gram orally of azithromycin is the recommended treatment. If pregnant females are unable to tolerate recommended treatment, these patients should have treatment with one of the following regimens:
In females who are pregnant or lactating the following medication treatment options are contraindicated: levofloxacin, ofloxacin, erythromycin estolate, and doxycycline. All patients should undergo repeat testing three months after treatment and reinfection should receive therapy with azithromycin.
Mycoplasma genitalium: the recommended antibiotic of choice is azithromycin 1 gram orally as a single dose, similar to treating Chlamydia. For those patients' infections resistant to treatment with azithromycin, moxifloxacin is a treatment alternative.[2][3][9]
Trichomonas vaginalis urethritis, including pregnant patients, should be treated with seven days of metronidazole 500 mg orally twice a day. Tolerance in pregnancy may be reduced due to significant nausea or vomiting so the length of treatment may be allowed to vary from five to seven days. [11]
The treatment regimens for the more common causes of urethritis are stated above. For the less common causes, the therapy still depends on the etiology. An example of urethritis caused by irritants from clothing, the therapy would include changes in soap and the reduction of friction with less tight fit clothing. Another example is that adenovirus is treated with supportive care involving hydration, NSAIDs, and bed rest due to no current medical therapy approved and is a self-limiting illness.
Genitourinary infections may affect one or more one portion of the genitourinary tract, simultaneously or independently. Other causes of similar symptoms in males include prostatitis, epididymitis, cystitis, proctitis, and chemical irritation. The differential diagnosis in female patients includes cervicitis, cystitis, and vaginitis.
Patients have an excellent prognosis with a high rate of cure when diagnosed and treated appropriately. Treatment for sexual partners should be addressed when appropriate for specific infectious organisms. Unfortunately, sexually active individuals are commonly reinfected by untreated partners. With persistent urethritis after treatment for the most common organisms, it is important to investigate for co-infections and other less common causative agents. It is important for prompt identification and treatment as several of the causative organisms do carry risk for unpleasant and damaging complications.
Complications for the most common causes of urethritis, including those from Neisseria gonorrhea, have shown associations with some rare complications including penile edema, periurethral abscesses, post-inflammatory urethral strictures, and penile lymphangitis. Conditions associated with Chlamydia trachomatis complications include pelvic inflammatory disease, infertility, ectopic pregnancy, Fitz-Hugh-Curtis syndrome, proctitis, and reactive arthritis. A complete reactive arthritis triad, also known as Reiter syndrome, includes urethritis, uveitis, and arthritis. This is a rare disease that may be caused by Chlamydia trachomatis and involve acute epididymitis, orchitis, and prostatitis.[6]
If an STI was diagnosed, it is important to educate the patient on safe sexual practices. This includes discussing with the patient for them to inform their partner(s) and encourage them to have themselves evaluated by a health care professional and pursue appropriate treatment. It is important to stress the likelihood of how a recurrence can occur even if their partner(s) are asymptomatic as they may have asymptomatic infections. Patients should be educated on refraining from intercourse until both the patient and partner(s) have been successfully treated and are without symptoms.
Diagnosing urethritis can be a challenge if patients do not feel comfortable discussing their sexual practices. For patients to feel at ease and disclose important history, a robust doctor-patient relationship must exist. Doctors should work closely with other staff to ensure patient comfort and a non-judgemental environment. Pertinent history can lead to different suspected organisms, and since treatment is organism-specific, it is imperative to maintain and establish this relationship early on.
Clinicians should work closely with a pharmacist to ensure the best antibiotic choices for treatment, with the pharmacist verifying appropriate coverage, dosing, and duration. Patient and community safety are affected by ensuring the prescribing of the best antibiotic and medication compliance. Nursing can chart progress and counsel the patient on compliance, as well as answering any patient questions, and reporting concerns or results to the clinical team. The patient's confidentiality is a priority as well as is reporting diseases.
By having an interprofessional team approach to testing and treating patients, it will maximize patient care benefit and medication compliance while eradicating the disease. [Level 5]
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[3] | Totten PA,Schwartz MA,Sjöström KE,Kenny GE,Handsfield HH,Weiss JB,Whittington WL, Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men. The Journal of infectious diseases. 2001 Jan 15 [PubMed PMID: 11120932] |
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[6] | Bachmann LH,Manhart LE,Martin DH,Seña AC,Dimitrakoff J,Jensen JS,Gaydos CA, Advances in the Understanding and Treatment of Male Urethritis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015 Dec 15 [PubMed PMID: 26602615] |
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[8] | Bradshaw CS,Tabrizi SN,Read TR,Garland SM,Hopkins CA,Moss LM,Fairley CK, Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure. The Journal of infectious diseases. 2006 Feb 1 [PubMed PMID: 16388480] |
[9] | Workowski KA,Berman SM, Centers for Disease Control and Prevention Sexually Transmitted Disease Treatment Guidelines. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011 Dec [PubMed PMID: 22080270] |
[10] | Taylor SN,DiCarlo RP,Martin DH, Comparison of methylene blue/gentian violet stain to Gram's stain for the rapid diagnosis of gonococcal urethritis in men. Sexually transmitted diseases. 2011 Nov [PubMed PMID: 21992973] |
[11] | National guideline for the management of Trichomonas vaginalis. Clinical Effectiveness Group (Association for Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sexually transmitted infections. 1999 Aug [PubMed PMID: 10616377] |