What is the next step in managing dysuria in a sexually active patient of reproductive age with negative urine culture, negative Chlamydia (sexually transmitted infection) and Gonorrhea (sexually transmitted infection) tests, and no hematuria (blood in urine)?

Management of Dysuria with Negative Cultures and STI Testing

In a sexually active patient with dysuria, negative urine culture, negative chlamydia/gonorrhea testing, and no hematuria, the next step is to test for Mycoplasma genitalium, as this organism is an established cause of urethritis that requires specific testing and treatment. 1

Diagnostic Considerations

Mycoplasma genitalium Testing

• M. genitalium is a well-documented cause of urethritis and cervicitis that will not be detected by standard chlamydia/gonorrhea testing. 2, 1
• Testing for M. genitalium is specifically recommended when patients have persistent urethritis or cervicitis with negative initial STI testing. 1
• This organism has been associated with urethritis in multiple studies and requires targeted nucleic acid amplification testing. 2

Confirm Objective Evidence of Urethritis

Before proceeding with additional antimicrobial therapy, document objective signs of urethral inflammation: 3

• Mucopurulent or purulent urethral discharge
• Positive leukocyte esterase on first-void urine
• ≥10 white blood cells per high-power field on microscopic examination of first-void urine sediment

Consider Non-Infectious Causes

If M. genitalium testing is negative or unavailable, evaluate for: 2, 1

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

• Symptoms must be present for at least 6 weeks with documented negative cultures. 2
• Characterized by bladder/pelvic pain and pressure associated with urinary frequency and strong urge to void. 2
• Document number of voids per day, sensation of constant urge, and character/severity of pain. 2
• Obtain a baseline voiding log to establish low-volume frequency pattern. 2

Other Non-Infectious Causes: 1, 4

• Bladder irritants (caffeine, acidic foods, alcohol)
• Vulvovaginal conditions (atrophic vaginitis, contact dermatitis)
• Trauma or mechanical irritation
• Urethral syndrome (acute dysuria-pyuria syndrome)

Treatment Approach

If M. genitalium is Suspected or Confirmed

• Azithromycin 1g orally as a single dose is particularly effective against M. genitalium. 3
• Alternative: Extended doxycycline 100mg orally twice daily for 7 days. 3

If Persistent Symptoms After Initial Treatment

For recurrent urethritis with negative testing: 3

• Metronidazole 2g orally single dose OR tinidazole 2g orally single dose
• PLUS azithromycin 1g orally single dose (if not previously used)
• This regimen covers Trichomonas vaginalis, which can cause dysuria with negative standard testing. 2

Partner Management

• All sex partners from the preceding 60 days should be evaluated, tested, and treated. 5, 3
• Partners should receive treatment effective against chlamydia regardless of specific etiology identified. 3
• Patients and partners must abstain from sexual intercourse until 7 days after therapy initiation and symptoms resolve. 3

Common Pitfalls to Avoid

• Do not assume all dysuria is UTI-related: In sexually active young women with pyuria but sterile cultures, chlamydia has been an important cause of acute dysuria-pyuria syndrome. 2
• Do not overlook sexual history: Only 17% of women with dysuria receive adequate sexual history screening in emergency settings, leading to missed STI diagnoses. 6
• Do not treat empirically without objective findings: Symptoms alone without documentation of urethral inflammation are not sufficient basis for antimicrobial re-treatment. 2
• Do not forget reinfection risk: Retest approximately 3 months after treatment due to high reinfection rates. 5, 3

When to Consider Cystoscopy

Cystoscopy is indicated if: 2

• Hunner lesions are suspected (these patients respond well to specific treatment)
• Symptoms persist despite appropriate treatment
• Need to exclude bladder cancer, stones, or foreign bodies in high-risk patients