What are the causes of sexually transmitted urethritis apart from Chlamydia (Chlamydia trachomatis), Gonococcus (Neisseria gonorrhoeae), and Mycoplasma (Mycoplasma genitalium)?

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From the Guidelines

Sexually transmitted urethritis can be caused by several pathogens beyond chlamydia, gonorrhea, and mycoplasma, including Trichomonas vaginalis, herpes simplex virus (HSV), adenovirus, and Ureaplasma urealyticum, as supported by the most recent guidelines 1.

Causes of Urethritis

The causes of sexually transmitted urethritis apart from Chlamydia, Gonococcus, and Mycoplasma include:

  • Trichomonas vaginalis, a protozoan parasite
  • Herpes simplex virus (HSV)
  • Adenovirus
  • Ureaplasma urealyticum Less common causes include bacterial pathogens like Escherichia coli during insertive anal intercourse, and candida species. Some cases remain idiopathic despite testing.

Diagnosis and Treatment

Proper diagnosis typically requires nucleic acid amplification tests, culture, or microscopy of urethral discharge 1. Treatment should be directed at the specific pathogen identified, with empiric therapy covering the most likely organisms while awaiting test results. For example, Trichomonas is treated with metronidazole 2g as a single oral dose or 500mg twice daily for 7 days, while HSV-related urethritis requires antiviral treatment with acyclovir 400mg three times daily for 7-10 days, valacyclovir 1g twice daily for 7-10 days, or famciclovir 250mg three times daily for 7-10 days. Ureaplasma urealyticum responds to doxycycline 100mg twice daily for 7 days or azithromycin 1g as a single dose.

Recent Guidelines

The European Association of Urology guidelines on urological infections, updated in 2024, emphasize the importance of differentiating between gonococcal urethritis (GU) and non-gonococcal urethritis (NGU), and highlight the role of Ureaplasma spp. in causing urethritis 1. The guidelines recommend empiric treatment for severe urethritis, while advising to delay treatment until guided by the results of nucleic acid amplification tests for mild cases. It is crucial to evaluate and treat all at-risk sexual partners while upholding patient confidentiality.

From the FDA Drug Label

Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae. All patients with sexually-transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate cultures for gonorrhea performed at the time of diagnosis. Appropriate antimicrobial therapy and follow-up tests for these diseases should be initiated if infection is confirmed Antimicrobial agents used in high doses for short periods of time to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis

The causes of sexually transmitted urethritis apart from Chlamydia, Gonococcus, and Mycoplasma are not explicitly stated in the drug label. However, it is mentioned that syphilis may be a cause of urethritis, as antimicrobial agents used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis 2.

From the Research

Causes of Sexually Transmitted Urethritis

Apart from Chlamydia (Chlamydia trachomatis), Gonococcus (Neisseria gonorrhoeae), and Mycoplasma (Mycoplasma genitalium), the causes of sexually transmitted urethritis include:

  • Ureaplasma urealyticum 3
  • Trichomonas vaginalis 3, 4, 5
  • Anaerobes 3
  • Herpes simplex virus (HSV) 3, 5
  • Adenovirus 3, 5

Diagnosis and Treatment

The diagnosis of urethritis is confirmed by demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained smear 3. An excess of mononuclear leucocytes in the smear indicates a viral etiology 3. Treatment options include doxycycline and azithromycin, with the choice of treatment depending on the suspected or proven pathogen 3, 6, 4.

Other Considerations

Up to half of the cases of urethritis are non-specific 3. Persistent or recurrent urethritis must be confirmed with microscopy, and reinfection and compliance must be considered 3. 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 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Management of non-gonococcal urethritis.

BMC infectious diseases, 2015

Research

Urethritis: Rapid Evidence Review.

American family physician, 2021

Research

[Urethritis-spectrum of pathogens, diagnostics and treatment].

Dermatologie (Heidelberg, Germany), 2023

Research

German evidence- and consensus-based guideline on the management of penile urethritis.

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 2025

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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