Treatment of Urethral Discharge Without Pyuria
For patients with urethral discharge but no pyuria, perform nucleic acid amplification testing (NAAT) for Neisseria gonorrhoeae and Chlamydia trachomatis on first-void urine or urethral swab, and if symptoms are mild, delay treatment until NAAT results guide pathogen-directed therapy. 1
Diagnostic Approach
The absence of pyuria does not exclude sexually transmitted urethritis. Research demonstrates that the sensitivity of urethral swabs and first-catch urine for detecting polymorphonuclear leukocytes is notably low for C. trachomatis (29%), Mycoplasma genitalium (50-62%), and Ureaplasma urealyticum (33%) in patients without visible discharge. 2 This means you cannot rely on pyuria to rule out infection.
Essential Testing
- Perform Gram stain of urethral discharge or smear for preliminary diagnosis of gonococcal urethritis (looking for Gram-negative intracellular diplococci). 1
- Obtain validated NAAT on first-void urine or urethral swab before empirical treatment to diagnose both chlamydial and gonococcal infections. 1
- Perform urethral swab culture if NAAT is positive for gonorrhea to assess antimicrobial resistance profiles. 1
Treatment Strategy Based on Symptom Severity
Mild Symptoms
Delay treatment until NAAT results are available to guide pathogen-directed therapy based on local resistance data. 1 This approach is strongly recommended by the 2024 European Association of Urology guidelines and avoids unnecessary antibiotic exposure while ensuring appropriate targeted therapy.
Severe Symptoms or Inability to Follow-Up
If the patient has severe urethritis or follow-up is uncertain, initiate empirical treatment immediately. 1
Empirical Treatment Regimens (When Indicated)
For Suspected Gonococcal Infection
- Ceftriaxone 1 g IM or IV single dose PLUS Azithromycin 1 g PO single dose 1, 3
- Alternative if cephalosporin allergy: Gentamicin 240 mg IM single dose plus azithromycin 2 g PO single dose 1
For Non-Gonococcal Urethritis (Unidentified Pathogen)
- Doxycycline 100 mg PO twice daily for 7 days 1
- Alternative: Azithromycin 500 mg PO on day 1, then 250 mg PO for 4 days 1
For Confirmed Chlamydia trachomatis
Critical Management Points
Sexual partners must be treated while maintaining patient confidentiality. 1, 4 This is essential to prevent reinfection and break the transmission chain.
Use pathogen-directed treatment based on local resistance data whenever possible. 1 The emergence of antimicrobial resistance, particularly in gonorrhea, makes culture and susceptibility testing increasingly important.
Common Pitfalls to Avoid
Do not dismiss urethral symptoms based solely on absence of pyuria. Studies show that 17-20% of patients with urethral discharge have indeterminate pathogens, and major pathogens like M. genitalium are frequently present even without classic inflammatory markers. 2
Do not rely on urethral discharge presence alone. Research demonstrates that asymptomatic NGU occurs in approximately 22% of sexually active men with multiple partners. 5
Ensure specific testing for C. trachomatis in every patient with urethral symptoms regardless of whether classic signs of urethritis (discharge, pyuria) are present. 2 The low sensitivity of traditional inflammatory markers means infections are frequently missed without molecular testing.
Consider Mycoplasma genitalium in persistent cases. This organism accounts for approximately one-third of nonchlamydial NGU cases and may require moxifloxacin 400 mg daily for 7-14 days if macrolide resistance is present. 1, 4