What is the diagnosis and treatment for non-gonococcal urethritis (NGU)?

From the Guidelines

Non-gonococcal urethritis should be treated with doxycycline 100mg orally twice daily for 7 days as the first-line treatment, as recommended by the most recent guidelines 1. The treatment of non-gonococcal urethritis (NGU) has evolved over time, with various antimicrobial regimens being recommended. According to the European Association of Urology guidelines on urological infections, published in 2024 1, doxycycline 100mg orally twice daily for 7 days is the recommended first-line treatment for NGU.

• Alternative treatments include azithromycin 500mg orally on day 1, followed by 250mg orally for 4 days 1.
• The choice of treatment should be based on the suspected causative organism, with common causes including Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and Trichomonas vaginalis.
• Patients with persistent or recurrent symptoms after initial therapy may require alternative treatments, such as moxifloxacin 400mg orally once daily for 7-14 days 1.
• Sexual partners from the past 60 days should be notified, evaluated, and treated to prevent reinfection, as recommended by the Centers for Disease Control and Prevention 1.
• Patients should abstain from sexual activity until therapy is completed and symptoms have resolved, and follow-up is recommended if symptoms persist after treatment 1.

From the FDA Drug Label

Nongonococcal urethritis (NGU) caused by C. trachomatis or U. urealyticum: 100 mg, by mouth, twice a day for 7 days. For adults with uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis, when tetracycline is contraindicated or not tolerated 500 mg of erythromycin by mouth four times a day for at least 7 days. For patients with nongonococcal urethritis caused by Ureaplasma urealyticum when tetracycline is contraindicated or not tolerated 500 mg of erythromycin by mouth four times a day for at least seven days.

The recommended treatment for non-gonococcal urethritis is:

• Doxycycline: 100 mg, by mouth, twice a day for 7 days 2
• Erythromycin: 500 mg, by mouth, four times a day for at least 7 days, when tetracycline is contraindicated or not tolerated 3

From the Research

Causes of Non-Gonococcal Urethritis

• Non-gonococcal urethritis (NGU) is the most common treatable sexually transmitted syndrome in men, with approximately 20-50% of cases being due to infection with Chlamydia trachomatis and 10-30% Mycoplasma genitalium 4
• Other causes of NGU include Ureaplasma urealyticum, Trichomonas vaginalis, anaerobes, Herpes simplex virus (HSV), and adenovirus 4
• Up to half of the cases of NGU are non-specific 4

Diagnosis of Non-Gonococcal Urethritis

• The diagnosis of urethritis is confirmed by demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained smear 4
• An excess of mononuclear leucocytes in the smear indicates a viral etiology 4
• Nucleic acid amplification tests (NAAT) for Neisseria gonorrhoeae, C. trachomatis, and M. genitalium should be performed 4
• If viral or protozoan etiology is suspected, NAAT for HSV, adenovirus, and T. vaginalis should be performed, if available 4

Treatment of Non-Gonococcal Urethritis

• Treatment options for NGU include doxycycline 100 mg twice daily for one week, or azithromycin 1 gram single dose or 1.5 gram distributed in five days 4
• Azithromycin has been shown to be effective in treating NGU, with cure rates comparable to doxycycline 5, 6, 7
• However, the use of azithromycin as first-line treatment without test of cure for M. genitalium and subsequent moxifloxacin treatment of macrolide-resistant strains may select and increase macrolide-resistant strains in the population 4
• Current partner(s) should be tested and treated with the same regimen, and should abstain from intercourse until both have completed treatment 4

Management of Persistent or Recurrent Non-Gonococcal Urethritis

• Persistent or recurrent NGU must be confirmed with microscopy, and reinfection and compliance must be considered 4
• If doxycycline was given as first therapy, azithromycin five days plus metronidazole 4-500 mg twice daily for 5-7 days should be given 4
• If azithromycin was prescribed as first therapy, doxycycline 100 mg twice daily for one week plus metronidazole, or moxifloxacin 400 mg orally once daily for 7-14 days should be given 4