Urethritis is inflammation of the urethra, classified as gonococcal (caused by Neisseria gonorrhoeae) or nongonococcal (most commonly Chlamydia trachomatis, Mycoplasma genitalium, or Trichomonas vaginalis). [1-2] It is one of the most common presentations of sexually transmitted infections in the ED and primary care setting. The following is a clinically focused summary organized for rapid decision-making.
1. History
- Discharge characterization: Color (clear/mucoid vs. mucopurulent vs. frankly purulent), volume, timing (morning "glue" vs. constant)
- Dysuria: Onset, severity, internal vs. meatal burning
- Urethral pruritus or irritation without discharge [1-2]
- Timing: Onset relative to last sexual contact; gonococcal urethritis typically presents 2–8 days after exposure, chlamydial urethritis 7–21 days [3]
- Sexual history: Number and gender of partners, new partners, condom use, oral/anal/vaginal contact, transactional sex [4]
- Prior STI history and treatment: Especially recent azithromycin use (raises concern for macrolide-resistant M. genitalium) [2][5]
- Important negatives: Hematuria, flank pain, fever, testicular pain/swelling, joint pain, skin lesions, eye symptoms
2. Alarm Features
- Testicular pain/swelling → epididymitis/orchitis [2][6]
- Fever + polyarthralgia + skin lesions (pustules/petechiae) → disseminated gonococcal infection (DGI) [2-3]
- Tenosynovitis (especially asymmetric, involving wrists/hands) → DGI [2]
- Abdominal pain in female partners → PID risk from untreated infection [7]
- Conjunctivitis → gonococcal autoinoculation or reactive arthritis (Reiter syndrome) [4]
- Urethral stricture symptoms (weak stream, straining) → rare complication of untreated gonococcal urethritis [3]
- Meningismus or new heart murmur → rare gonococcal endocarditis or meningitis [2]
3. Medications
Empiric treatment (etiology unknown): [1]
- Ceftriaxone 500 mg IM × 1doxycycline 100 mg PO BID × 7 days
Organism-specific regimens: [1][7]
Key medication pearls:
- Azithromycin co-treatment for gonorrhea is no longer recommended per 2021 CDC guidelines [7-8]
- Doxycycline is now preferred over azithromycin for chlamydia due to higher microbiologic cure rates [7][10]
- Azithromycin 1 g remains the recommended chlamydia treatment in pregnancy [7]
- Contraindicated: Doxycycline in pregnancy; fluoroquinolones in pregnancy and pediatric patients
4. Diet
- No specific dietary triggers or restrictions
- Encourage adequate hydration to promote urinary flow and comfort
- Advise avoiding alcohol during metronidazole therapy (disulfiram-like reaction)
5. Review of Systems
- GU: Dysuria, discharge, frequency, urgency, hematuria, testicular pain/swelling, pain with ejaculation [4]
- MSK: Joint pain, swelling (DGI, reactive arthritis) [4]
- Derm: Rash, skin lesions (pustules, papules, ulcers) [2]
- Ophthalmologic: Eye redness, discharge (conjunctivitis) [4]
- GI/Anorectal: Rectal pain, discharge, bleeding, tenesmus (proctitis if receptive anal intercourse) [4]
- Constitutional: Fever, chills, malaise (suggests dissemination or ascending infection)
- Oropharyngeal: Sore throat, exudates (pharyngeal gonorrhea) [3]
6. Collateral History and Family History
- Partner notification is critical: Partners should be evaluated and treated; expedited partner therapy (EPT) is permitted in most states [9]
- Ask about partner symptoms (discharge, dysuria, abnormal bleeding)
- Social context: Incarceration, substance use, transactional sex — all increase STI risk [4]
- Family history is generally not contributory, except terminal complement deficiency (hereditary) increases risk of DGI [2]
7. Risk Factors
- Age <25 years [4]
- Multiple or new sexual partners [4]
- Inconsistent condom use [4]
- Men who have sex with men (MSM) [1]
- Prior STI history [4]
- Transactional sex [4]
- Substance use (particularly in MSM) [4]
- M. genitalium specifically more common in younger men, smokers, and those with multiple partners [1]
- T. vaginalis more common in heterosexual men, older age, incarcerated populations, and high-prevalence geographic areas [1-2]
8. Differential Diagnosis
- Urinary tract infection / cystitis — more common in women; culture-positive with uropathogens
- Prostatitis — suprapubic/perineal pain, prostatic tenderness on DRE, LUTS [11]
- Epididymitis — unilateral testicular pain/swelling, positive Prehn sign [6]
- Herpes simplex urethritis — meatitis, genital ulceration, severe dysuria; more common with HSV-1 via oral-genital contact [2]
- Reactive arthritis (Reiter syndrome) — triad of urethritis, conjunctivitis, arthritis [4]
- Urethral foreign body or trauma
- Chemical/irritant urethritis — soaps, spermicides
- Adenoviral urethritis — dysuria, meatitis, conjunctivitis; associated with oral-genital contact [2]
- Non-infectious/idiopathic NGU — accounts for up to ~50% of NGU cases with no identifiable pathogen [2]
9. Past Medical History
- Prior STI episodes and treatments received (especially azithromycin — raises macrolide resistance concern for M. genitalium) [5]
- HIV status — immunosuppression may alter presentation and increase susceptibility
- History of urethral stricture or instrumentation
- Complement deficiency (risk for DGI) [2]
- Use of eculizumab (inhibits terminal complement → increased DGI risk) [2]
10. Physical Exam
- Urethral meatus: Discharge (express if not spontaneously visible — "milking" the urethra), erythema, meatitis [1]
- Inguinal lymph nodes: Lymphadenopathy (consider LGV if tender, unilateral) [4]
- Testicular exam: Tenderness, swelling, epididymal induration (epididymitis) [6]
- Skin: Pustular or petechial acral lesions (DGI), genital ulcers (HSV, syphilis) [2]
- Joints: Tenosynovitis, effusion (DGI, reactive arthritis) [2]
- Oropharynx: Exudates, erythema (pharyngeal gonorrhea) [3]
- Conjunctivae: Injection, discharge [4]
- Rectal exam: If anorectal symptoms present — discharge, tenderness
- The CDC recommends examination of skin, pharynx, lymph nodes, anogenital area, and neurologic system when evaluating for STIs [1]
11. Lab Studies
- NAAT for N. gonorrhoeae and C. trachomatis on first-void urine (preferred specimen in males) — this is the gold standard diagnostic test [1-3]
- Urinalysis: First-void; ≥10 WBC/HPF or positive leukocyte esterase supports diagnosis [1]
- Gram stain of urethral discharge (if available): ≥2 WBC/oil immersion field confirms urethritis; gram-negative intracellular diplococci (GNID) = presumptive gonorrhea [2]
- HIV, syphilis (RPR/VDRL), hepatitis B screening — recommended for all patients with urethritis and STI risk factors [1]
- Hepatitis C screening in MSM and those on PrEP [7]
- **M. genitalium NAAT — reserve for persistent/recurrent NGU, not initial presentation [2]
- **T. vaginalis NAAT — consider in heterosexual men, recurrent urethritis, or high-prevalence areas [1-2]
- Urine culture — not routinely needed; reserve for suspected antimicrobial-resistant gonorrhea or atypical presentations [1]
12. Imaging
- Imaging is generally unnecessary for uncomplicated urethritis
- Scrotal ultrasound if epididymitis or testicular torsion is suspected
- Pelvic ultrasound in female patients with concern for PID/tubo-ovarian abscess
- Joint imaging if DGI with septic arthritis is suspected
13. Special Tests
- Point-of-care NAAT (binx health io CT/NG, Visby Medical Sexual Health Test) — provides same-day results, reduces loss to follow-up and overtreatment [4]
- Gram stain / methylene blue / gentian violet stain of urethral secretions — highly sensitive and specific POC test for confirming urethritis and identifying gonococcal infection [2]
- Macrolide resistance testing for M. genitalium — recommended when available to guide therapy; not yet widely available in the US [2][5]
The following figure illustrates a systematic approach to evaluating dysuria in male patients:
14. ECG
- Not routinely indicated for uncomplicated urethritis
- Obtain ECG if DGI with suspected endocarditis (new murmur, persistent bacteremia, embolic phenomena) [2]
15. Assessment
Clinical summary: Urethritis is predominantly an STI-driven condition. N. gonorrhoeae and C. trachomatis account for the majority of cases, with M. genitalium increasingly recognized as a cause of persistent/recurrent NGU (15–25% of NGU cases). [2-3] Approximately 50% of NGU cases remain idiopathic even with comprehensive testing. [2]
Severity stratification:
- Uncomplicated: Isolated urethral symptoms, no systemic signs → outpatient management
- Complicated: Epididymitis, prostatitis, DGI, reactive arthritis → escalation of care
Typical vs. atypical presentations:
- Gonococcal: Profuse purulent discharge, acute onset 2–8 days post-exposure [3]
- Chlamydial/NGU: Scant mucoid discharge, milder dysuria, may be asymptomatic [1]
- A significant proportion of infections (55–87% of urogenital gonorrhea in men in population-based studies) may be asymptomatic [3]
16. Treatment Plan
Initial management:
- Empiric treatment at time of diagnosis — do not wait for NAAT results if clinical suspicion is high: [1-2]
- First dose should be directly observed in clinic when possible [2]
- If Gram stain shows no GNID (nongonococcal urethritis): doxycycline 100 mg PO BID × 7 days alone is appropriate [2]
Persistent/recurrent NGU (symptoms persist after initial treatment):
- Ensure adherence and rule out reinfection (re-exposure)
- Test for M. genitalium (NAAT) and T. vaginalis [2]
- M. genitalium: Doxycycline 100 mg BID × 7 days → moxifloxacin 400 mg daily × 7 days (resistance-guided therapy preferred if available) [2-3]
- T. vaginalis: Metronidazole 2 g PO × 1 [1]
- Persistent NGU after M. genitalium and T. vaginalis treatment → refer to ID or urology [2]
Partner management:
- All sexual partners within the preceding 60 days should be referred for evaluation and treatment [4]
- Expedited partner therapy (EPT) is an option in most states [9]
17. Disposition
- Discharge (vast majority): Uncomplicated urethritis is managed entirely as an outpatient [1]
- Observation/Admission criteria:
- Suspected DGI (fever, polyarthralgia, skin lesions, tenosynovitis) → hospitalization and ID consultation recommended [2]
- Suspected gonococcal endocarditis or meningitis [2]
- Inability to tolerate oral medications or concern for nonadherence in complicated cases
- Specialist consultation triggers:
- Persistent/recurrent NGU after appropriate treatment for M. genitalium and T. vaginalis → ID or urology referral [2]
- Suspected antimicrobial-resistant gonorrhea
- DGI → ID consultation [2]
18. Follow Up / Return Precautions
- Abstain from sexual intercourse for 7 days after single-dose treatment, or until completion of a 7-day course AND symptom resolution AND partner treatment [1][4]
- Repeat testing (test of reinfection): 3 months after treatment, or at first visit within 12 months [1][4]
- Do NOT repeat NAAT <3 weeks after treatment — risk of false-positive results from residual nucleic acid [1]
- Test-of-cure is NOT needed for urogenital gonorrhea but IS recommended for pharyngeal gonorrhea (14 days post-treatment) [7]
- Report gonorrhea and chlamydia to the local health department (both are reportable conditions) [2]
Return precautions — advise patients to return immediately for:
- Persistent or worsening discharge/dysuria after completing treatment
- Testicular pain or swelling
- Fever, joint pain, or rash
- Eye redness or discharge
Expected course: Symptoms typically improve within 48–72 hours of appropriate antibiotic therapy. If no improvement, reassess for resistant organisms, alternative diagnoses, or nonadherence. [6]
References
1. Urethritis: Rapid Evidence Review. — Sell J, Nasir M, Courchesne C. American Family Physician. 2021.
2. Urethritis: Rapid Evidence Review. — Sell J, Nasir M, Courchesne C. American Family Physician. 2021.
3. Urethritis: Rapid Evidence Review. — Sell J, Nasir M, Courchesne C. American Family Physician. 2021.
4. Sexually Transmitted Infections Treatment Guidelines, 2021. — Workowski KA, Bachmann LH, Chan PA, et al. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2021.
5. Sexually Transmitted Infections Treatment Guidelines, 2021. — Workowski KA, Bachmann LH, Chan PA, et al. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2021.
6. Diagnosis and Treatment of Sexually Transmitted Infections: A Review. — Tuddenham S, Hamill MM, Ghanem KG. The Journal of the American Medical Association. 2022.
7. Diagnosis and Treatment of Sexually Transmitted Infections: A Review. — Tuddenham S, Hamill MM, Ghanem KG. The Journal of the American Medical Association. 2022.
8. Chlamydial and Gonococcal Infections: Screening, Diagnosis, and Treatment. — Yonke N, Aragón M, Phillips JK. American Family Physician. 2022.
9. Chlamydial and Gonococcal Infections: Screening, Diagnosis, and Treatment. — Yonke N, Aragón M, Phillips JK. American Family Physician. 2022.
10. Emerging and Reemerging Sexually Transmitted Infections. — Williamson DA, Chen MY. The New England Journal of Medicine. 2020.
11. Emerging and Reemerging Sexually Transmitted Infections. — Williamson DA, Chen MY. The New England Journal of Medicine. 2020.
12. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
13. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
14. Sexually Transmitted Infections: Updates From the 2021 CDC Guidelines. — Dalby J, Stoner BP. American Family Physician. 2022.
15. Sexually Transmitted Infections: Updates From the 2021 CDC Guidelines. — Dalby J, Stoner BP. American Family Physician. 2022.
16. Management of Neisseria Gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines. — Barbee LA, St Cyr SB. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2022.
17. Management of Neisseria Gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines. — Barbee LA, St Cyr SB. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2022.
18. Sexually Transmitted Infections: Updated Guideline From the CDC. — Klein DA, Valerio CR, Cofield ZN. American Family Physician. 2022.
19. Sexually Transmitted Infections: Updated Guideline From the CDC. — Klein DA, Valerio CR, Cofield ZN. American Family Physician. 2022.
20. Diagnosis and Management of Uncomplicated Chlamydia Trachomatis Infections in Adolescents and Adults: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines. — Geisler WM, Hocking JS, Darville T, Batteiger BE, Brunham RC. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2022.
21. Diagnosis and Management of Uncomplicated Chlamydia Trachomatis Infections in Adolescents and Adults: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines. — Geisler WM, Hocking JS, Darville T, Batteiger BE, Brunham RC. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2022.
22. Dysuria: Evaluation and Differential Diagnosis in Adults. — Hoffman A, Dolezal KA, Powell R. American Family Physician. 2025.
23. Dysuria: Evaluation and Differential Diagnosis in Adults. — Hoffman A, Dolezal KA, Powell R. American Family Physician. 2025.