What is the best course of treatment for a patient with a history of Non-Specific Urethritis (NSU) presenting with urinary challenges, such as dysuria, frequency, and urgency?

Management of Urinary Challenges in a Patient with History of Non-Specific Urethritis

Treat empirically with doxycycline 100 mg orally twice daily for 7 days while simultaneously testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium using nucleic acid amplification testing (NAAT). 1, 2

Initial Diagnostic Confirmation

Before initiating treatment, document urethritis using objective criteria:

• Mucopurulent or purulent urethral discharge on examination 1
• Gram stain showing ≥5 white blood cells per oil immersion field 1
• Positive leukocyte esterase test on first-void urine OR ≥10 white blood cells per high-power field on urine microscopy 1, 2

Obtain NAAT testing on urethral swab or first-void urine for N. gonorrhoeae and C. trachomatis at the initial visit. 1, 2 If initial testing is negative but symptoms persist, test specifically for M. genitalium and Ureaplasma urealyticum, as these organisms cause 20-40% of non-gonococcal urethritis cases but are not detected on standard STD panels. 2, 3

First-Line Empiric Treatment

Doxycycline 100 mg orally twice daily for 7 days is the preferred initial regimen for non-gonococcal urethritis. 1, 4, 3 Alternative option is azithromycin 1 g orally as a single dose, though this should be avoided as first-line therapy without test of cure for M. genitalium, as it will select for macrolide-resistant strains. 3

If gonorrhea cannot be excluded clinically, add ceftriaxone 250 mg IM as a single dose to the doxycycline regimen. 1

Critical Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen, regardless of symptoms or test results. 1, 2 Both patient and partners must abstain from sexual intercourse for 7 days after treatment initiation and until symptoms have completely resolved. 1

Symptomatic Relief

For dysuria, frequency, and urgency symptoms, phenazopyridine may provide symptomatic relief but should not exceed 2 days of use and should not delay definitive treatment of the underlying infection. 5 The analgesic action may reduce the need for systemic analgesics during the interval before antibiotics control the infection. 5

Follow-Up Strategy for Persistent Symptoms

If symptoms persist after completing the initial 7-day doxycycline course:

First reassessment (1 week post-treatment):

• Re-confirm urethritis with microscopy showing ≥5 PMNLs per oil immersion field 2, 3
• Consider reinfection and assess treatment compliance 3
• If M. genitalium was detected, perform test of cure no earlier than 3 weeks after treatment initiation 3

Treatment for persistent/recurrent urethritis after doxycycline:

• Azithromycin 1.5 g distributed over 5 days (300 mg day 1, then 250 mg daily for 4 days) PLUS metronidazole 400-500 mg twice daily for 5-7 days 3
• If M. genitalium is confirmed positive on test of cure or macrolide resistance is suspected, switch to moxifloxacin 400 mg orally once daily for 7-14 days 3

Second reassessment (4 weeks if symptoms continue):

• Consider alternative diagnoses beyond infectious urethritis 2
• Evaluate for anatomical abnormalities such as urethral strictures or false passages, which occur in 40% of chronic cases 6
• Consider cystoscopy if hematuria, recurrent infections, or suspected anatomic anomaly (strictures, false passage) are present 7

Key Pathogen Considerations

• C. trachomatis accounts for 23-55% of non-gonococcal urethritis cases 1, 3
• M. genitalium accounts for 10-30% of cases and responds better to azithromycin than doxycycline 1, 3
• Ureaplasma urealyticum, anaerobes (Bacteroides, Peptostreptococci), and viral causes (HSV, adenovirus) account for remaining cases 3, 6

Critical Complications to Prevent

Untreated urethritis leads to:

• Epididymitis requiring 10 days of doxycycline 100 mg twice daily 4
• Reiter's syndrome (reactive arthritis) 1
• Infection transmission to female partners with risk of pelvic inflammatory disease 1

All patients with sexually transmitted urethritis should receive syphilis serology and HIV counseling/testing at diagnosis. 1

Common Pitfalls to Avoid

• Do not perform surveillance urine cultures in asymptomatic patients, as bacteriuria does not predict symptomatic UTI and promotes antibiotic resistance 7
• Do not treat asymptomatic bacteriuria except in pregnant patients or prior to urologic procedures 7
• Do not use azithromycin as first-line therapy without M. genitalium testing and test of cure, as this selects for macrolide-resistant strains 3
• Symptoms alone without objective signs (PMNLs on microscopy) are insufficient for retreatment 1
• Ensure adequate fluid intake with doxycycline to reduce risk of esophageal irritation and ulceration 4