What could be causing ongoing dysuria (painful urination) without fever or chills, unresponsive to antibiotics, and a normal urinalysis (urine dip test)?

Dysuria with Normal Urinalysis and No Response to Antibiotics

This patient likely has non-infectious dysuria, and antibiotics should be discontinued immediately as they provide no benefit and may cause harm. 1, 2

Differential Diagnosis to Consider

The normal urine dipstick (negative for leukocyte esterase and nitrites) effectively rules out bacterial cystitis, making continued antibiotic therapy inappropriate. 1 The key differential diagnoses include:

Sexually Transmitted Infections (Most Common in This Scenario)

• Urethritis from Chlamydia trachomatis, Mycoplasma genitalium, or Ureaplasma urealyticum is the leading consideration when dysuria persists despite negative urinalysis and failed antibiotic treatment. 1, 2
• These pathogens cause urethral inflammation without pyuria or bacteriuria on standard urine testing. 1
• Obtain urethral swab or first-void urine for nucleic acid amplification testing (NAAT) for Chlamydia and Gonorrhea immediately. 2
• If initial STI testing is negative but symptoms persist, test specifically for Mycoplasma genitalium, as this is increasingly recognized as a cause of persistent urethritis. 2

Non-Infectious Causes

• Bladder irritants: caffeine, alcohol, spicy foods, artificial sweeteners, and acidic beverages can cause dysuria without infection. 2, 3
• Interstitial cystitis/bladder pain syndrome: characterized by chronic pelvic pain, urinary frequency, and urgency without infection. 3
• Urethral syndrome: dysuria with frequency and urgency but sterile urine cultures, accounting for up to 30% of dysuria cases in women. 4
• Vulvovaginal conditions: atrophic vaginitis (in postmenopausal women), contact dermatitis, lichen sclerosus, or herpes simplex virus can cause external dysuria. 2, 3

Immediate Diagnostic Workup

Stop antibiotics now - they prolong symptoms when no bacterial infection exists and increase resistance risk. 1, 4

Essential Testing

• NAAT testing for Chlamydia trachomatis and Neisseria gonorrhoeae on first-void urine or urethral/vaginal swab. 2
• Pelvic examination (if female) to assess for vaginal discharge, cervicitis, vulvar lesions, or signs of atrophic vaginitis. 2, 3
• Genital examination (if male) for urethral discharge, penile lesions, or testicular tenderness. 1

If Initial STI Testing is Negative

• Mycoplasma genitalium NAAT testing should be performed for persistent urethritis. 2
• Urine culture (not just dipstick) if not already done, as some fastidious organisms may be missed. 5
• Consider post-void residual volume measurement if voiding dysfunction suspected. 1

Management Based on Findings

If STI Identified

• Chlamydia: Doxycycline 100mg twice daily for 7 days (preferred) or azithromycin 1g single dose. 1
• Gonorrhea: Ceftriaxone 500mg IM single dose. 1
• Mycoplasma genitalium: Doxycycline 100mg twice daily for 7 days followed by moxifloxacin 400mg daily for 7 days (if macrolide-resistant). 1, 2
• Partner notification and treatment is mandatory. 1

If No Infection Found

• Eliminate bladder irritants: advise avoiding caffeine, alcohol, spicy foods, and acidic beverages for 2 weeks. 2, 3
• Increase fluid intake to dilute urine and reduce irritation. 1
• Phenazopyridine 200mg three times daily for 2 days maximum can provide symptomatic relief while investigating cause. 2
• Consider referral to urology if symptoms persist beyond 2-4 weeks despite conservative measures. 1, 3

Critical Pitfalls to Avoid

• Do not continue empiric antibiotics - this increases resistance, causes adverse effects, and provides no benefit when urinalysis is negative. 1, 4
• Do not assume all dysuria is UTI - only 50-60% of dysuria cases are actually bacterial cystitis. 2, 3
• Do not miss STI testing - this is the most common cause of culture-negative dysuria in sexually active patients. 1, 2
• Do not overlook vaginal discharge - its presence significantly decreases likelihood of UTI and suggests cervicitis or vaginitis instead. 2

Red Flags Requiring Urgent Evaluation

• Fever, flank pain, or systemic symptoms suggest upper tract involvement requiring imaging and different management. 1, 6
• Gross hematuria after infection resolution warrants urologic evaluation for stones, malignancy, or structural abnormalities. 1
• Recurrent symptoms within 2 weeks suggest bacterial persistence from anatomic abnormality requiring imaging. 1