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Urethritis
Maria Harsha Wusu, MD, MSEd
Joanne Wilkinson, MD, MSc
image BASICS
DESCRIPTION
  • Inflammation of the urethra
  • Common manifestation of sexually transmitted infection
  • Frequently associated with dysuria, pruritus, and/or urethral discharge; classified as gonococcal (caused by Neisseria gonorrhoeae) and nongonococcal (caused by other bacteria, or less commonly autoimmune disorders [Reiter syndrome], trauma, or chemical irritation)
EPIDEMIOLOGY
Incidence
  • In 2013, there were >330,000 reported cases of gonorrhea, with a rate of 106.1 cases per 100,000 population (0.6% decrease since 2012) (1)
  • In 2013, there were >1.4 million reported cases of Chlamydia trachomatis infection, or 446.6 cases per 100,000 population (1.5% decrease since 2012) (2)
  • Rate of chlamydial infection in U.S. women was more than twice that of men, reflecting higher rates of screening (1).
  • Highest incidences of gonorrhea and chlamydia among young men and women, ages 15 to 24 years (1)
ETIOLOGY AND PATHOPHYSIOLOGY
  • Most common cause is infection via sexual transmission of N. gonorrhoeae, a gram-negative diplococcus.
  • N. gonorrhoeae interacts with nonciliated epithelial cells→ cellular invasion→ inflammation, neutrophil production, bacterial cell phagocytosis (2)
  • Sexually transmitted C. trachomatis infection is the most common cause of nongonococcal urethritis.
  • Other established pathogens
    • Mycoplasma genitalium
    • Trichomonas vaginalis
    • Ureaplasma urealyticum
    • Herpes simplex virus (rare)
    • Adenovirus (rare)
  • Noninfectious causes (generally rare)
    • Chemical irritants (i.e., soaps, shampoos, douches, spermicides)
    • Foreign bodies
    • Urethral instrumentation
RISK FACTORS
  • One or more sex partner(s)
  • New sex partner
  • History of or coexisting STI
  • Sex partner with concurrent partner(s)
  • Inconsistent condom use outside of a mutually monogamous relationship
  • Exchanging sex for money or drugs
  • Member of population with increased prevalence of infection, including incarcerated populations, military recruits, black and Hispanic persons
GENERAL PREVENTION
  • Use of male condoms, female condoms, or cervical diaphragms
  • Abstinence or reduction in the number of sex partners
  • Behavioral counseling
COMMONLY ASSOCIATED CONDITIONS
image DIAGNOSIS
  • Chief complaint
    • Urethral discharge (mucopurulent suggestive of N. gonorrhoeae)
    • Dysuria
    • Erythema of the urethral meatus
    • Symptom onset 2 to 8 days following exposure
  • History
    • Sexual history, including condom use, number of partners, sexual behaviors
    • Previous STIs
    • Substance abuse
    • Recent travel
    • Symptoms indicative of complications or additional sites of infection (i.e., men: testicular pain and swelling, anal itching, rectal pain or bleeding; women: lower abdominal pain, dyspareunia, irregular vaginal bleeding)
  • Male GU exam (possible findings)
    • Urethral discharge
    • Meatal erythema
    • Testicular tenderness
    • Palpate scrotum to check for epididymitis or orchitis.
    • Check for ulcers.
    • Check for inguinal lymphadenopathy.
  • Female GU exam (possible findings)
    • Vaginal discharge
    • Endocervical discharge, hyperemia, and/or friability
Pediatric Considerations
Pediatric infections with gonorrhea and chlamydia after the neonatal period strongly suggest sexual contact. If indicated, investigations should be initiated promptly (3).
DIFFERENTIAL DIAGNOSIS
  • Other genitourinary tract diseases
    • Cystitis/urinary tract infection
    • Epididymitis
    • Prostatitis
    • PID
    • Pyelonephritis
  • Vaginal atrophy, especially in postmenopausal women
  • Stevens-Johnson syndrome
  • Reiter syndrome: uveitis, urethritis, arthritis
  • Wegener granulomatosis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Gram-stain diagnosis of urethritis if: urethral secretions with ≥2 WBC per oil immersion field, mucopurulent or purulent discharge, or first void urine sediment with ≥10 WBC per high-power field (hpf) (3)
  • Gonorrhea
    • Nucleic acid amplification test (NAAT): in men: first void urine preferred (90-100% sensitivity, 97-100% specificity for gonorrhea); in women: vaginal swab preferred (patient or clinician collected), end cervical swab acceptable, first void urine may detect 10% fewer infections (3)[A]
    • Culture: traditional gold standard—most commonly used in cases of suspected treatment resistance (3)
  • Chlamydia
    • NAAT: in men: first catch urine equal to urethral swab (85-95% sensitivity, 93-99% specificity); in women: vaginal swab preferred (patient or clinician collected), end cervical swab acceptable, first void urine may detect 10% fewer infections (3)[A]
    • Tissue cultures: traditional gold standard, but currently NOT recommended (3)
    • If concern for trichomonas: NAAT (urine, urethral, vaginal, or endocervical swab), wet mount, or culture
    • There is no FDA-approved diagnostic test available for M. genitalium.
Follow-Up Tests & Special Considerations
  • Test of cure for chlamydia and gonorrhea is recommended in pregnant women or when treatment noncompliance is suspected (3).
  • Repeat testing in 3 months recommended due to rates of reinfection (3)
  • HIV infection: Persons with HIV infection should receive the same treatment as patients without HIV infection (3).
Diagnostic Procedures/Other
Urethrocystoscopy for cases with suspected foreign body, intraurethral warts, urethral stricture
Test Interpretation
Urethral strictures (untreated gonorrhea), intraurethral lesions (venereal warts, congenital anomalies), PID, or tubo-ovarian abscesses are possible.
P.1083

image TREATMENT
GENERAL MEASURES
  • Most cases can be treated in the outpatient setting.
  • Single-dose regimens with direct observation preferred (3)
MEDICATION
First Line
  • Gonorrhea
    • Ceftriaxone 250 mg IM plus either: azithromycin 1 g PO × 1 dose (preferred) OR doxycycline 100 mg PO BID for 7 days (if azithromycin allergy) (3)[A]
    • For children ≤45 kg: ceftriaxone 25 to 50 mg/kg (max 125 mg) IM × 1 dose. For children >45 kg: use adult dosing.
  • Chlamydia
    • Azithromycin: 1 g PO × 1 dose OR
    • Doxycycline: 100 mg PO BID for 7 days (3)[A]
    • Alternative regimens (all for 7 days): erythromycin base 500 mg PO QID, erythromycin ethylsuccinate 800 mg PO QID, levofloxacin 500 mg daily, OR ofloxacin 300 mg PO BID
  • Trichomonas
    • Metronidazole: 2 g PO × 1 dose
  • Recurrent and resistant urethritis
    • Metronidazole: 2 mg PO single dose OR tinidazole 2 g PO single dose plus azithromycin 1 g PO × 1 dose
  • Contraindications: sensitivity to any of the indicated medications
  • Precautions: Patients taking tetracyclines may have increased photosensitivity.
  • Significant possible interactions
    • Tetracyclines should not be taken with milk products or antacids.
    • Oral contraceptives may be rendered less effective by oral antibiotics. Patients and partners should use a back-up method of birth control for the remainder of the cycle.
Pregnancy Considerations
  • Chlamydia: All pregnant women <25 years and older women at increased risk should be screened for chlamydia at their first prenatal visit and again in the 3rd trimester. Women with chlamydia infections should be treated, have a documented TOC 3 to 4 weeks after treatment, and retested in 3 months (3).
  • Gonorrhea: All pregnant women under <25 years and older women at increased risk should be screened for gonorrhea at their first prenatal visit and again in the third trimester. Women with gonorrhea infections should be treated and be retested in 3 months (3).
  • Tetracyclines and quinolones are contraindicated.
  • Avoid erythromycin estolate because of an increased risk of cholestatic jaundice.
  • Single-dose therapy is recommended.
Second Line
  • Gonorrhea: If ceftriaxone is not an option, cefixime 400 mg PO × 1 dose plus either: azithromycin 1 g PO × 1 dose OR doxycycline 100 mg PO BID for 7 days (if azithromycin allergy); followed by a TOC in 1 week (3).
  • Chlamydia alternative regimens (all for 7 days): erythromycin base 500 mg PO QID, erythromycin ethylsuccinate 800 mg PO QID, levofloxacin 500 mg daily, OR ofloxacin 300 mg PO BID (3)
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Sexual activity should be avoided for 7 days following administration of single-dose therapy or until completion of multiday regimen.
  • All sexual partners who came in contact with the patient within 60 days should be referred for evaluation, testing, and presumptive treatment (3).
  • Expedited partner therapy (EPT) is an acceptable alternative. EPT—the practice of treating the diagnosed patient's sex partner(s) for chlamydia or gonorrhea by providing medications or prescriptions to the patient to provide to the partner(s) without clinical evaluation (3).
Patient Monitoring
  • Instruct patients to return if symptoms persist or recur after completing treatment.
  • Test of cure in 3 to 4 weeks in pregnant women suspected of nonadherence, reinfection, persistent symptoms
  • Screen for reinfection in all patients at 3 months.
DIET
Avoid alcohol when taking metronidazole.
PATIENT EDUCATION
  • Behavioral counseling interventions are recommended. Evidence of benefit increase with intensity of intervention (4).
  • Successful approaches include basic information about STIs and transmission, assess risk for transmission, include training skills (i.e., condom use, communication about safe sex, problem solving, goal setting) (4).
PROGNOSIS
If the diagnosis is firmly established, appropriate medications are prescribed and the patient is compliant with treatment; relief of symptoms occurs within days and the problem will resolve without squeal.
REFERENCES
1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2013. Atlanta, GA: U.S. Department of Health and Human Services; 2014.
2. LeFevre ML. Screening for chlamydia and gonorrhea: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(12):902-910.
3. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137.
4. O'Connor EA, Lin JS, Burda BU, et al. Behavioral sexual risk-reduction counseling in primary care to prevent sexually transmitted infections: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2014;161(12):874-883.
Additional Reading
&NA;
U.S. Preventive Services Task Force. Final Recommendation Statement. Gonorrhea and Chlamydia: Screening 2014. http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/chlamydia-and-gonorrhea-screening. Accessed 2015.
See Also
&NA;
  • Chlamydia Infection (Sexually Transmitted); Epididymitis; Gonococcal Infections; Pelvic Inflammatory Disease (PID); Prostatitis; Urinary Tract Infection (UTI) in Females; Urinary Tract Infection (UTI) in Males; Vulvovaginitis, Estrogen Deficient; Vulvovaginitis, Prepubescent
  • Algorithms: Dysuria; Genital Ulcers; Urethral Discharge
Codes
&NA;
ICD10
  • N34.2 Other urethritis
  • A56.01 Chlamydial cystitis and urethritis
  • A54.01 Gonococcal cystitis and urethritis, unspecified
Clinical Pearls
&NA;
  • Inflammation of the urethra, frequently associated with dysuria, pruritus, and/or urethral discharge
  • Common manifestation of STI
  • Classified as gonococcal (caused by N. gonorrhoeae) and nongonococcal
  • Nucleic acid amplification test (NAAT) preferred method of diagnosis for men and women
  • Single-dose regimens with direct observation preferred
  • In cases of gonorrhea or chlamydia infection, in person or expedited partner therapy (EPT) recommended for all partners of patients within the last 60 days
  • Given that risk factors for gonorrhea and chlamydia indicate risk for other STIs, screening for HIV, RPR, Hepatitis C, and Hepatitis B may also be indicated.
  • Repeat testing for gonorrhea and chlamydia in 3 months recommended due to rates of reinfection.
  • Special considerations in pediatric and pregnant populations
  • Treatment in persons with HIV infection is the same as in patients without HIV infection.
  • Health care providers are required to report all gonorrhea and chlamydia infections in accordance with local and state requirements.