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This is a corrected version of the article that appeared in print.

Am Fam Physician. 2021;103(9):553-558

Patient information: See related handout on urethritis, written by the authors of this article.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Urethritis refers to inflammation of the urethra and is classified as gonococcal (caused by Neisseria gonorrhoeae) or nongonococcal in origin (most commonly caused by Chlamydia trachomatis, Mycoplasma genitalium, or Trichomonas vaginalis). The most common signs and symptoms include dysuria, mucopurulent urethral discharge, urethral discomfort, and erythema. Diagnostic criteria include typical signs, symptoms, or history of exposure in addition to mucopurulent discharge, Gram stain of urethral secretions showing at least two white blood cells per oil immersion field, first-void urinalysis showing at least 10 white blood cells per high-power field, or a positive leukocyte esterase result with first-void urine. First-line empiric treatment consists of ceftriaxone and doxycycline; however, the antibiotic regimen may be targeted to the isolated organism. Repeat testing is not recommended less than three weeks after treatment because false-positive results are possible during this time. Patients treated for a sexually transmitted infection should have repeat screening in three months, with shared decision-making about future screening intervals. Patients treated for urethritis should abstain from sex for seven days after the start of treatment, until their partners have been adequately treated, and until their symptoms have fully resolved.

Urethritis refers to inflammation of the urethra. It is classified as gonococcal (caused by Neisseria gonorrhoeae) or nongonococcal in origin. Nongonococcal urethritis can be caused by several other organisms; Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis are the most common. The differential diagnosis of urethritis is summarized in Table 1.

Chemical irritation
Chronic pelvic pain syndrome
Epididymitis
Genital herpes
Mucositis
Prostatitis (acute or chronic)
Trauma
Urinary tract infection

Epidemiology

  • In 2018, the incidence of chlamydial urethritis was 381 cases per 100,000 U.S. men, making it the most common reportable condition and the most common type of urethritis in men. The number of reported cases of chlamydia increased 36% in U.S. men and women from 2008 to 2018.1

  • In 2018, the incidence of gonococcal urethritis was 213 cases per 100,000 U.S. men.1,2

  • Table 2 lists common bacterial isolates in patients with nongonococcal urethritis.3 Approximately one-half of nongonococcal cases have no clear etiology.

  • M. genitalium causes 15% to 20% of nongonococcal urethritis cases and higher rates of recurrent urethritis.4 The prevalence of M. genitalium isolates is 1.3% in the general population and 3.2% in men who have sex with men (MSM).5 M. genitalium is more common in men who are younger, who smoke, and who have multiple sex partners.6

  • T. vaginalis is a less common cause of urethritis. It was present in urine samples from 0.5% of men in the 2013–2016 cohort of the National Health and Nutrition Examination Survey,7 and its prevalence is as high as 6.6% to 11% in metropolitan areas with high prevalence of sexually transmitted infections (STIs).8,9 T. vaginalis infection is more common among people who are older or incarcerated; men who have sex with women; people with multiple sex partners; and when the local prevalence is high (more than 2% in symptomatic women).3,4,9,10

  • Ureaplasma urealyticum infection is associated with nongonococcal urethritis.11

  • Herpes simplex virus, adenovirus, and Haemophilus influenzae are rare causes of urethritis.

OrganismPrevalence (%)
Chlamydia trachomatis11 to 50
Mycoplasma genitalium6 to 50
Ureaplasma urealyticum5 to 26
Trichomonas vaginalis1 to 20

Clinical Features

  • Table 3 lists typical signs and symptoms of urethritis3,4,12; the most common is mucopurulent urethral discharge.

  • People with urethral chlamydia are more likely to be asymptomatic than those with urethral gonorrhea (42% vs. 10%).2

Dysuria (> 50% of patients)
Erythema of the penile tip or urethral meatus
Inguinal lymphadenopathy or ulcers
Pain or tenderness in testis, epididymis, or scrotum
Proctitis, anal pruritus, rectal pain or bleeding, or continual need to defecate
Rectal mucosal friability, purulent discharge, or perianal lesions
Urethral discharge (mucopurulent in > 80% of patients)
Urethral discomfort or pruritus

Diagnosis

  • In addition to examination of the genital area in people with urethritis symptoms, the Centers for Disease Control and Prevention (CDC) recommends examination of the skin, pharynx, lymph nodes, anogenital area, and neurologic system when evaluating for STIs.13

  • Urethritis should be suspected based on the presence of typical signs and symptoms, such as dysuria, urethral discharge, or urethral erythema.

  • The diagnosis can be confirmed using the criteria listed in Table 4.4

  • First-void urine samples are preferred when testing for N. gonorrhoeae or C. trachomatis infection using a nucleic acid amplification test (NAAT).4,14 First-catch urine (i.e., the initial 10 to 20 mL of the urinary stream, ideally collected at least 20 to 60 minutes after the last micturition) is a reasonable alternative with similar sensitivity.1517 In both methods, the urethral meatus should not be cleaned before the sample is collected.

  • Urine culture with antimicrobial sensitivity testing should be reserved for cases of gonorrhea with suspected antimicrobial resistance.

  • Gonococcal urethritis is indicated by the presence of polymorphonuclear cells and gram-negative diplococci on Gram stain of urethral secretions.

  • Testing for T. vaginalis infection by urethral swab culture or NAAT should be considered for people with recurrent urethritis or in areas or populations with a high prevalence. NAAT has higher sensitivity and specificity than culture.

  • The U.S. Food and Drug Administration approved a test for M. genitalium infection in January 2019,18 but no randomized trials have evaluated the cost effectiveness of routinely testing patients with urethritis. The CDC recommends that M. genitalium infection be considered in cases of persistent or recurrent urethritis, even if testing is not available locally.4

  • Testing for U. urealyticum infection in patients with urethritis is not routinely recommended because a positive test result does not confirm causality.3,11

  • Testing for syphilis, HIV infection, and hepatitis B should be considered for patients with urethritis and STI risk factors (e.g., multiple sex partners, suspected exposure, MSM).4

  • In sexually active MSM with chlamydia or gonorrhea diagnosed by NAAT, extragenital (oral and/or anal) test results are positive in more than 70% of those with normal urine samples.2,19

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