Nongonococcal Urethritis

Background

• Nongonococcal urethritis (NGU) refers to a urethral infection not caused by Neisseria gonorrhoeae.
• Most cases are sexually transmitted.
• The 3 most commonly identified causes of NGU, in order of prevalence, are:
  • Chlamydia trachomatis
  • Mycoplasma genitalium
  • Trichomonas vaginalis
• Symptoms associated with NGU are similar to those with gonococcal urethritis, and include purulent discharge, dysuria and urethral pruritus in men.

Evaluation

• Confirm diagnosis of urethritis in men, based on the presence of one of the following criteria:
  • Gram stain of urethral secretions with ≥ 5 white blood cells (WBC) per oil immersion field (preferred method)
  • mucopurulent or purulent discharge on exam
  • positive leukocyte esterase test on first-void urine (FVU)
  • microscopic examination of first-void urine sediment demonstrating ≥ 10 WBC per high power field
• As infection with either gonococcus or chlamydia is a reportable illness and would mandate partner therapy, test all patients for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests (NAATs) (Strong recommendation).
• Diagnosis of nongonococcal urethritis (NGU) is made when N. gonorrhoeae is not identified as the causative pathogen by either NAAT or demonstration of diplococci on Gram stain.
• Additional testing is typically not needed before initiating empiric treatment for NGU, which is directed at both C. trachomatis and Mycoplasma genitalium.
• For patients with recurrent or persistent urethritis following treatment, consider testing for Trichomonas vaginalis and Mycoplasma genitalium; options include:
  • culture of urethral swabs, semen or urine sediment from men for Trichomonas vaginalis
  • nucleic acid amplification test using urine or urethral swab specimens for Trichomonas vaginalis and Mycoplasma genitalium
• Test for other sexually transmitted infections including HIV in patients with suspected NGU.

Management

• If point-of-care diagnostics are not available to confirm the diagnosis of urethritis, treat empirically for both Neisseria gonorrhoeae and Chlamydia trachomatis.
• Centers for Disease Control and Prevention (CDC) recommendations for first-line empiric therapy for both organisms is a single dose of ceftriaxone plus doxycycline 100 mg orally twice daily for 7 days:
  • For persons < 150 kg, give ceftriaxone 500 mg intramuscularly in a single dose in combination with doxycycline.
  • For persons ≥ 150 kg, give ceftriaxone 1 g intramuscularly in a single dose in combination with doxycycline.
• CDC recommendation for first-line therapy for nongonococcal urethritis (NGU) is doxycycline 100 mg orally twice daily for 7 days.
• Optimal therapy for Mycoplasma genitalium should be based on antibiotic resistance testing.
  • If isolate is macrolide sensitive, give doxycycline 100 mg orally 2 times daily for 7 days followed by azithromycin 1 g orally single dose then 500 mg/day orally for 3 days.
  • If isolate is macrolide resistant or if resistance testing is not available, give doxycycline 100 mg orally 2 times daily for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days.
• Give medications at time of clinic visit and observe first dose when possible.
• Instruct patients to abstain from sexual intercourse for 7 days after single-dose therapy or completing a 7-day regimen.
• Patients should return for evaluation if they experience persistent or recurrent symptoms after completion of treatment.
• For patients with recurrent and persistent urethritis following treatment:
  • Consider retreatment with the same regimen if nonadherence or reexposure is suspected.
  • If there is treatment failure or an alternate diagnosis is suspected, consider additional testing for Trichomonas vaginalis and Mycoplasma genitalium and empiric treatment while awaiting results with either:
    • metronidazole 2 g orally in a single dose or tinidazole 2 g orally in a single dose for suspected T. vaginalis infection.
    • doxycycline 100 mg orally twice daily for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days for suspected M. genitalium infection.
• Patients should refer all sex partners within previous 60 days for evaluation and empiric treatment.
• Follow-up with retesting at 3-6 months is recommended for all patients due to high rates of reinfection in this population.