What is the recommended antibiotic treatment for non-gonococcal urethritis (NGU)?

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Last updated: April 29, 2025View editorial policy

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From the Guidelines

The recommended first-line antibiotic treatment for non-gonococcal urethritis (NGU) is doxycycline 100 mg orally twice daily for 7 days, as suggested by the European Association of Urology guidelines in 2024 1. This regimen is effective against Chlamydia trachomatis, which is the most common bacterial cause of NGU. An alternative treatment is azithromycin 500 mg orally on day 1,250 mg orally for 4 days, though this is now considered less preferred due to emerging resistance concerns, as noted in the guidelines 1. For patients who cannot take tetracyclines, other options can be considered, such as levofloxacin 500 mg orally once daily for 7 days. If symptoms persist after initial treatment, further evaluation and alternative treatments may be necessary, such as moxifloxacin for macrolide-resistant Mycoplasma genitalium, as suggested in the guidelines 1. Patients should abstain from sexual activity for 7 days after starting treatment and until symptoms resolve. Partners from the previous 60 days should be evaluated and treated regardless of symptoms to prevent reinfection, as recommended in the guidelines from the Centers for Disease Control and Prevention 1. Treatment failure may occur due to antibiotic resistance, particularly with M. genitalium, or reinfection from untreated partners, so follow-up evaluation is important if symptoms persist. Key considerations in managing NGU include:

  • Prompt initiation of treatment to reduce symptoms and prevent complications
  • Selection of an appropriate antibiotic regimen based on the likely causative pathogen and local resistance patterns
  • Partner notification and treatment to prevent reinfection
  • Follow-up evaluation to assess treatment response and detect potential treatment failures.

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. Non-gonoccocal urethritis and cervicitisOne single 1 gram dose

The recommended antibiotic treatment for non-gonococcal urethritis is:

  • Doxycycline: 100 mg, by mouth, twice a day for 7 days 2
  • Azithromycin: One single 1 gram dose 3

From the Research

Non-Gonococcal Urethritis Antibiotic Treatment

  • Non-gonococcal urethritis (NGU) is a common sexually transmitted infection, with approximately 20-50% of cases caused by Chlamydia trachomatis and 10-30% by Mycoplasma genitalium 4.
  • The diagnosis of NGU is confirmed by demonstrating an excess of polymorphonuclear leucocytes (PMNLs) in a stained smear, and treatment options include doxycycline 100 mg twice a day 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 clinical cure rates comparable to doxycycline in several studies 5, 6, 7.
  • A single dose of azithromycin has been found to be as effective as a 7-day course of doxycycline in achieving clinical cure in men with NGU 5, 7.
  • Azithromycin has also been shown to be effective in treating NGU negative for Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum, with a single dose of 1 g azithromycin resulting in no signs of urethral inflammation in 84.2% of patients 8.

Treatment Options

  • Doxycycline 100 mg twice a day for one week 4
  • Azithromycin 1 gram single dose or 1.5 gram distributed in five days 4
  • Azithromycin 1 g in a single dose, or 500 mg in a single dose on day 1 followed by 250 mg once daily for 2 days 6
  • A single dose of 1 g azithromycin for NMNUNCNGU (nonmycoplasmal, nonureaplasmal, nonchlamydial NGU) 8

Considerations

  • If positive for M. genitalium, test of cure samples should be collected no earlier than three weeks after start of treatment, and moxifloxacin 400 mg 7-14 days may be indicated if positive in test of cure 4.
  • Current partner(s) should be tested and treated with the same regimen, and should abstain from intercourse until both have completed treatment 4.
  • Persistent or recurrent NGU must be confirmed with microscopy, and reinfection and compliance must be considered 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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