Practice Essentials
Urethral discharge, dysuria, and exposure to a sexually transmitted infection (STI) are frequent presentations of urethritis in the male population. Research has focused on cost-effective antibiotic therapy and concern for emergence of antibiotic resistance with both typical and atypical organisms. The goal of initial therapy is to optimize compliance and prevent recurrence of this disease, which is predominantly sexually transmitted. [1, 2, 3, 4, 5, 6, 7, 8] Urethritis usually resolves without complications, even if left untreated, yet it can result in urethral stricture, stenosis, or abscess formation in rare cases. Urethritis can occur in a continuum with concomitant seminal vesiculitis and epididymitis. [9] Recurrent urethritis may occur from reinfection, therapeutic failure, or "venereophobia," an old term describing fear of recurrence where men can induce urethral inflammation and drainage (negative by white blood cell or Gram stain criteria) by repeatedly milking the urethra, checking for infection. [10] Urethritis is predominantly a disease of adolescent and adult men. The prevalence is greatest in men younger than 25 years. [11, 12, 13, 14, 15]
Neisseria gonorrhoeae causes gonococcal urethritis (GU) and is a gram-negative intracellular diplococcus that can also be involved in epididymitis, prostatitis, proctitis, septic arthritis, disseminated infection, pharyngitis, and osteomyelitis, as well as pelvic inflammatory disease, infertility, endometritis, Bartholin gland abscess in women, and conjunctivitis in neonates. The most common cause of nongonococcal urethritis (NGU) is Chlamydia trachomatis (15-40% of cases), followed by Mycoplasma genitalium (15-20% of cases). Other causes of NGU include Trichomonas vaginalis, herpes simplex virus, Epstein Barr virus, and Adenovirus. [7, 11, 16]
Diagnostic testing
Because gonorrhea and chlamydia are reportable to the state health departments in the United States, [11] confirmatory diagnostic testing is recommended. Options include Gram stain, culture, direct immunofluorescence, enzyme immunoassay, polymerase chain reaction, nucleic acid hybridization, or nucleic acid amplification testing (NAAT). Nucleic acid amplification testing of a first-catch urine specimen is the most sensitive test (in a male) for gonorrhea or chlamydia. Sensitivity of NAAT testing for chlamydia is optimized by waiting a minimum of 20 minutes after a recent void, [17] although prior experts recommended a 1-hour wait.
Testing for Trichomonas is too often neglected, but recommended, for recurrent or persistent symptoms. Wet mount preparations are insensitive, but NAAT and polymerase chain reaction (PCR) testing are highly sensitive for T. vaginalis from first-catch urine specimens.
NAAT testing for M genitalium from first-catch urine, urethral, or penile meatal specimens is now FDA approved, although it may not be routinely available in many settings, and is recommended in cases of recurrent NGU.
For persistent infection following treatment, unrelated to reexposure, send a specimen to the Center for Disease Control and Prevention (CDC) for drug-resistance testing.
Rescreening for C trachomatis and N gonorrhoeae is recommended 3 months after treatment.
Human immunodeficiency virus (HIV) and syphilis testing is recommended on the initial visit for STI concern and again at follow-up.
Symptoms
Gonococcal urethritis (GU) has a more abrupt onset of symptoms, commonly within 3-4 days and usually within 7 days, with opaque yellow or white discharge and significant dysuria. Neisseria gonorrhoeae, the cause of gonococcal urethritis, is a gram-negative intracellular diplococcus. In contrast, non-GU (NGU) has an insidious onset, minimal dysuria, and scant or mucoid or clear discharge. Nongonococcal urethritis can be caused by various organisms.
Symptoms of urethritis spontaneously resolve over time, regardless of treatment. Administer antibiotics that cover both GU and NGU. Regardless of symptoms, administer antibiotics to the following individuals:
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Patients with positive Gram stain or culture results
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All sexual partners of the above patients
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Patients with negative Gram stain results and a history consistent with urethritis who are not likely to return for follow-up and/or are likely to continue transmitting infection
Treatment
Antibiotic therapy should cover both gonococcal urethritis and nongonococcal urethritis. Current CDC guidelines recommend a higher single dose of 500 mg ceftriaxone IM for GU (1 g for men ≥ 150 kg), and doxycycline 100 mg orally twice daily for 7 days for NGU. [11] If concomitant treatment for NGU is not provided, the risk of postgonococcal urethritis is approximately 50%. In most situations, optimal treatment is with the first dose of antibiotic administered in the emergency department or the physician's office.
Pathophysiology
Inflammation of the urethra is more frequently infectious than posttraumatic, with sexually transmitted infections (STIs) being the most common cause. Sexually transmitted urethritis is classified either as gonococcal urethritis (GU) following infection with Neisseria gonorrhoeae or as nongonococcal urethritis (NGU).
For cases of NGU, Chlamydia trachomatis remains a primary concern, although Mycoplasma genitalium and Trichomonas vaginalis are increasingly recognized as important pathogens, and, less commonly, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, and Gardnerella vaginalis. [18, 19, 20]
In one study of 424 men with signs and symptoms of acute urthritis, 127 (30%) were found to be infected with N gonorrhoeae. In 297 men with nongonococcal urethritis, C trachomatis was detected in 143 (48.1%). In 154 men with nonchlamydial nongonococcal urethritis, M genitalium (22.7%), M hominis (5.8%), U parvum (9.1%), U urealyticum (19.5%), H influenzae (14.3%), N meningitidis (3.9%), T vaginalis (1.3%), human adenovirus (16.2%), and herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. [21]
M genitalium, not routinely tested by NAAT or PCR in many locations, may cause up to 10-30% of NGU cases [1, 2, 22] and, like chlamydia, may be associated with human immunodeficiency virus (HIV), human papillomavirus (HPV), and herpes simplex transmission and infection. M genitalium has been associated with treatment failure of previously recommended single-dose therapy because of macrolide resistance, [3, 4, 23, 24, 25, 22, 26] with potential for quinolone resistance as well. [4, 24, 25, 27] Couldwell et al described rates of resistance of 15% for quinolones and 43% for macrolides in 143 M genitalium specimens in Australia. [25]
Idiopathic urethritis, defined as urethritis in the absence of nucleic acid amplification testing (NAAT) evidence for the most common infectious causes (N gonorrhoeae, C trachomatis, M genitalium, and T vaginalis), may be considered the largest category. [28, 29]
Unusual infectious causes of urethritis include herpes genitalis, syphilis, mycobacterium, adenovirus, and cytomegalovirus, as well as typical bacteria (usually gram-negative rods) associated with cystitis in the presence of urethral stricture or following insertive anal sex.
Urethritis following trauma is less common, but it can occur with intermittent catheterization or after urethral instrumentation or foreign body insertion. Fewer than 20% of patients practicing intermittent catheterization suffer urethritis; however, use of latex instead of silicone catheters significantly increases this risk. Symptoms of urethritis (urethral syndrome) can also be due to sensitivity to chemicals in spermicidal or contraceptive jellies or foams.
Idiopathic urethritis of childhood is of uncertain cause, perhaps related to dysfunctional elimination syndrome, [30] and presents as blood-stained urethral discharge, bleeding between micturition, or dysuria in the 5- to 15-year-old male, and it can result in urethral stricture. [31, 32]
Urethritis involves local mucous membrane epithelial cell damage or invasion by an infectious agent (bacterial, viral, or fungal) followed by inflammatory changes, including accumulation of leukocytes and chemical mediators (antibodies, cytokines, and interleukins) with resultant swelling, discharge, and pain.
