What is the best course of action for a 24-year-old male patient presenting with dysuria, negative STI cultures, negative urine cultures, and a negative CT scan?

Management of Dysuria in a 24-Year-Old Male with Negative Cultures

This patient most likely has either interstitial cystitis/bladder pain syndrome (IC/BPS) or urethritis from an atypical pathogen such as Mycoplasma genitalium, and should be evaluated with a detailed sexual history and consideration of testing for atypical STIs before initiating empiric treatment. 1, 2

Initial Diagnostic Considerations

Rule Out Atypical STIs First

• Mycoplasma genitalium is detected in 5-22% of patients with dysuria and negative routine STI testing, and standard UTI antibiotics are ineffective against this pathogen 2
• Up to 74% of patients with confirmed STIs demonstrate sterile pyuria (pyuria with negative urine cultures), making this a common clinical scenario 3
• Obtain a detailed sexual history including timing of symptoms relative to sexual activity, number of partners, and specific sexual practices to assess STI risk 4
• Consider testing for Mycoplasma genitalium via nucleic acid amplification test (NAAT) on first-catch urine, as this pathogen requires specific antibiotic therapy (typically azithromycin or moxifloxacin) 2

Evaluate for Interstitial Cystitis/Bladder Pain Syndrome

• IC/BPS should be considered when symptoms persist for at least 6 weeks with documented negative cultures 1
• Key diagnostic features include: bladder/pelvic pain or pressure, urinary frequency (document with voiding diary), strong urge to void, and dysuria in the absence of infection 1
• A brief neurological exam should be performed to rule out occult neurologic problems, and evaluate for incomplete bladder emptying 1
• Baseline voiding symptoms and pain levels should be documented using validated tools (genitourinary pain index, interstitial cystitis symptom index, or visual analog scale) 1

When to Perform Cystoscopy

Cystoscopy is NOT routinely indicated for uncomplicated dysuria with negative cultures, but specific indications include 1:

• Suspicion of Hunner lesions (a specific IC/BPS phenotype that responds well to treatment)
• Hematuria requiring evaluation
• Recurrent symptoms refractory to initial management
• Concern for bladder stones, foreign body, or anatomic abnormality

Treatment Algorithm

If Sexual History Suggests STI Risk:

1. Test for atypical STIs including Mycoplasma genitalium using NAAT on first-catch urine 4, 2
2. Consider empiric treatment with azithromycin 1g single dose if high suspicion and follow-up uncertain 2
3. Ensure testing was performed at appropriate anatomical sites based on sexual practices (pharyngeal/rectal swabs for men who have sex with men) 4

If IC/BPS is Suspected (symptoms >6 weeks):

1. Begin with behavioral and non-pharmacologic interventions as first-line therapy 1:

   • Patient education about the chronic nature of the condition
   • Stress management techniques
   • Dietary modifications (avoiding bladder irritants)
   • Pelvic floor physical therapy if pelvic floor dysfunction present

2. Oral medications can be offered concurrently with behavioral therapies 1:

   • Amitriptyline (starting 10-25mg at bedtime, titrating up)
   • Pentosan polysulfate (with counseling about potential retinal toxicity with long-term use)
   • Hydroxyzine for patients with allergic/histamine component

3. Bladder instillations and procedures reserved for refractory cases 1

Critical Pitfalls to Avoid

• Do NOT empirically treat with fluoroquinolones or standard UTI antibiotics when cultures are negative, as this promotes antimicrobial resistance without addressing the underlying cause 1, 3
• Do NOT assume pyuria equals bacterial UTI - 74% of patients with confirmed STIs have sterile pyuria 3
• Do NOT overlook Mycoplasma genitalium - this pathogen causes dysuria but requires specific testing and treatment different from standard UTI therapy 2
• Do NOT perform cystoscopy routinely in young males with dysuria and negative cultures unless specific indications exist 1
• Recognize that nitrite-positive urines in the setting of STIs are actually more likely to have negative cultures (59% false positive rate) 3

Follow-Up Strategy

• If symptoms persist beyond 6 weeks despite addressing STI concerns, transition focus to IC/BPS management with multimodal therapy 1
• Document response to interventions using the same validated symptom scales established at baseline 1
• Consider urology referral if symptoms are refractory to initial behavioral and oral medication trials 1