What is the most likely cause of a clear urethral discharge in a sexually active young adult when Gram stain shows many neutrophils but no organisms?

Chlamydia trachomatis is the Most Likely Organism

In a sexually active young adult with clear urethral discharge and numerous white blood cells but no organisms on Gram stain, Chlamydia trachomatis is the most likely causative pathogen, accounting for 23-55% of nongonococcal urethritis cases. 1

Diagnostic Reasoning

The clinical scenario describes nongonococcal urethritis (NGU), which is diagnosed when Gram-negative intracellular diplococci (gonorrhea) cannot be identified on urethral smears despite evidence of urethral inflammation. 1

Why Chlamydia is Most Likely:

• C. trachomatis is the most frequent cause of NGU, responsible for 15-55% of cases depending on the population studied 1
• Clear or mucopurulent discharge is characteristic of chlamydial infection, in contrast to the typically more purulent discharge of gonorrhea 2
• Chlamydial urethritis in men often produces less profuse discharge than gonorrhea and symptoms may be mild or absent 2
• The presence of numerous WBCs (>5 per oil immersion field) confirms urethritis, and the absence of organisms on Gram stain rules out gonorrhea 1

Other Organisms in the Differential

Ureaplasma urealyticum:

• Implicated in up to one-third of nonchlamydial NGU cases 1
• However, it is less common than Chlamydia overall and specific diagnostic tests are not routinely indicated 1
• Ureaplasma frequently colonizes healthy individuals without causing symptoms 3

Mycoplasma genitalium:

• Also implicated in up to one-third of nonchlamydial NGU cases 1
• Specific testing is not routinely available or indicated in most clinical settings 1

Trichomonas vaginalis:

• Sometimes causes NGU but is much less common than Chlamydia in men 1
• Diagnostic testing is reserved for cases not responsive to standard therapy 1

Critical Management Points

Empiric treatment should cover both gonorrhea and chlamydia when diagnostic tools are unavailable or follow-up is uncertain, because coinfection rates can reach 20-40% in certain populations 2

Treatment Recommendations:

• Azithromycin 1 g orally as a single dose OR Doxycycline 100 mg orally twice daily for 7 days 1
• Single-dose regimens improve compliance and allow directly observed therapy 1
• All sexual partners from the past 60 days must be evaluated and treated 1

Common Pitfalls to Avoid:

• Do not rely on discharge characteristics alone for diagnosis—substantial overlap exists between gonorrhea and chlamydia presentations 2
• Do not assume absence of discharge excludes infection—asymptomatic carriage is common in both sexes 2
• Do not treat for Ureaplasma without documented urethritis symptoms or objective signs of inflammation 3
• Do not defer testing for both gonorrhea and chlamydia—nucleic acid amplification tests (NAATs) are required for accurate detection and are more sensitive than culture 1, 2