What is the best course of action for a 21-year-old male patient presenting with penile ache, urinary frequency, urgency, and a feeling of wetness in his underwear, without dysuria (painful urination), and no recent history of STI (sexually transmitted infection) screenings provided?

Clinical Approach to Penile Ache with Urinary Frequency and Urgency in a Young Male

This 21-year-old male most likely has nongonococcal urethritis (NGU) and should be treated empirically with doxycycline 100 mg orally twice daily for 7 days, while simultaneously testing for gonorrhea and chlamydia. 1, 2

Diagnostic Evaluation

Confirm Urethritis

The diagnosis of urethritis requires objective evidence, not just symptoms. You need to document at least one of the following 1, 3:

• Visible urethral discharge (mucoid or purulent)
• ≥5 white blood cells per oil immersion field on urethral Gram stain 2
• ≥10 white blood cells per high-power field in first-void urine 1, 2
• Positive leukocyte esterase test on first-void urine 3

The "wet feeling in underwear" likely represents urethral discharge, which is the hallmark of urethritis 1. The absence of dysuria does not exclude urethritis—many infections are asymptomatic or present with minimal symptoms 1.

Essential Testing

• Urinalysis and microscopy on first-void urine to document pyuria 4
• Nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae on first-void urine 1
• Urethral Gram stain if available to look for gram-negative intracellular diplococci (gonorrhea) and quantify white blood cells 1

Testing is strongly recommended because it improves partner notification, treatment compliance, and allows for reportable disease surveillance 1.

Treatment Algorithm

Immediate Empiric Therapy

Start treatment immediately without waiting for test results 1, 2:

• Doxycycline 100 mg orally twice daily for 7 days (first-line for NGU) 1, 2
• PLUS Ceftriaxone 500 mg IM single dose (or cefixime 400 mg orally single dose) to cover gonorrhea if testing is unavailable 1

The rationale: C. trachomatis causes only 23-55% of NGU cases 2. Ureaplasma urealyticum accounts for 20-40%, Trichomonas vaginalis 2-5%, and Mycoplasma genitalium is increasingly recognized 2. Since standard STI panels may miss these organisms, empiric doxycycline covers the broadest spectrum 2.

Alternative Regimens (if doxycycline contraindicated)

• Erythromycin base 500 mg orally 4 times daily for 7 days 1, 2
• Erythromycin ethylsuccinate 800 mg orally 4 times daily for 7 days 1, 2

Critical Instructions to Patient

• Abstain from sexual intercourse for 7 days after completing therapy 1
• All sexual partners from the past 60 days must be evaluated and treated 1, 2
• Dispense medication on-site and directly observe the first dose to maximize compliance 1

Differential Diagnosis Considerations

Rule Out Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)

While less likely given the acute presentation, CP/CPPS should be considered if symptoms persist beyond 3 months 1. CP/CPPS presents with 1:

• Pain in perineum, suprapubic region, testicles, or tip of penis
• Pain exacerbated by urination or ejaculation
• Sense of incomplete bladder emptying
• Urinary frequency

The key distinction: CP/CPPS is defined by pain as the primary symptom lasting >3 months, whereas urethritis typically presents more acutely 1.

Consider Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)

Though uncommon in young males, IC/BPS can present with 1:

• Bladder/pelvic pain, pressure, or discomfort
• Urinary frequency and urgency
• Symptoms present for at least 6 weeks 1

However, IC/BPS patients typically void to relieve pain, whereas overactive bladder patients void to avoid incontinence 1. The "ache sensation" and "wet feeling" make urethritis far more likely in this 21-year-old.

Follow-Up Strategy

Reassessment Timing

• Return only if symptoms persist or recur after completing therapy 1, 2
• If no improvement within 3 days of starting treatment, re-evaluate the diagnosis 2

Persistent Symptoms (>3 months)

If symptoms continue beyond 3 months despite appropriate treatment, consider 1:

• Chronic prostatitis/chronic pelvic pain syndrome
• Referral to urology for further evaluation
• Possible cystoscopy if Hunner lesions (IC/BPS) suspected 1

Common Pitfalls to Avoid

1. Do not treat based on symptoms alone without objective evidence of urethritis 1. The leukocyte esterase test or microscopy must confirm inflammation.

2. Do not assume absence of dysuria excludes infection 1. Many urethritis cases are minimally symptomatic.

3. Do not delay partner treatment 1, 2. Expedited partner therapy (giving prescriptions for untested partners) is CDC-recommended and legal in many states 3.

4. Do not perform test-of-cure at 3-4 weeks unless symptoms persist 1. However, retest at 3-6 months is recommended because reinfection rates are high 1.

5. Do not miss HIV and syphilis testing 1. All patients diagnosed with a new STD should receive testing for other infections.

Partner Management

All sexual partners within the preceding 60 days require evaluation and empiric treatment 1, 2:

• Partners should receive the same chlamydia-effective regimen even if the patient's specific etiology is unknown 1
• Expedited partner treatment is an acceptable alternative when partners cannot be examined 1, 3