In a 50‑year‑old patient with dysuria and a negative urinalysis, what is the appropriate next step in evaluation and management?

Dysuria with Negative Urinalysis: Evaluation and Management

In a 50-year-old patient with burning during urination but a negative urinalysis, the most likely diagnosis is non-infectious urethritis, bladder irritation, or early sexually transmitted infection, and empiric antibiotics for UTI should NOT be prescribed. 1

Immediate Diagnostic Approach

The negative urinalysis effectively rules out bacterial cystitis, as the combination of negative leukocyte esterase and negative nitrite has a 90.5% negative predictive value for UTI. 1, 2 This patient requires a different diagnostic pathway than typical UTI evaluation.

Key Historical Features to Elicit

• Pattern of dysuria: Does it improve with increased fluid intake (suggesting mechanical/chemical irritation) or persist regardless of hydration status (suggesting infection)? 1
• Sexual history: Recent new partner, unprotected intercourse, or symptoms in partner suggest sexually transmitted infection (STI). 3, 4
• Associated symptoms: Presence of urethral discharge, vaginal discharge (in women), testicular pain, or pelvic pain points toward STI rather than UTI. 3, 5
• Timing and triggers: Dysuria after specific activities (intercourse, new hygiene products, medications) suggests non-infectious causes. 5
• Age and gender considerations: In men over 35, consider prostatitis; in younger patients, STIs are more common. 4

Differential Diagnosis Algorithm

Most Likely Causes in This Population

For sexually active patients (especially <35 years):

• Chlamydia trachomatis urethritis/cervicitis is the most common cause of dysuria with negative urinalysis in younger adults. 3, 4
• Neisseria gonorrhoeae should be considered, particularly with urethral discharge. 3
• Mycoplasma genitalium testing is recommended if initial STI testing is negative but symptoms persist. 3

For all patients:

• Chemical or mechanical irritation from soaps, douches, spermicides, or tight clothing can cause dysuria without infection. 5
• Bladder irritants including caffeine, alcohol, acidic foods, or medications may produce symptoms. 5
• Interstitial cystitis/bladder pain syndrome presents with chronic dysuria and negative cultures. 5

For older men (>35 years):

• Prostatitis should be considered even without fever, requiring digital rectal examination. 4
• Benign prostatic hyperplasia with secondary inflammation can cause dysuria. 4

For postmenopausal women:

• Genitourinary syndrome of menopause (atrophic vaginitis) commonly causes dysuria without infection. 5

Recommended Testing Strategy

First-Line Testing

• STI screening is mandatory in sexually active patients: nucleic acid amplification testing (NAAT) for Chlamydia and Gonorrhea from first-void urine (men) or vaginal swab (women). 3
• Pelvic examination in women to assess for vaginal discharge, cervicitis, or atrophic changes; vaginal discharge decreases likelihood of UTI. 3, 5
• Digital rectal examination in men to evaluate for prostatic tenderness or enlargement. 4

Second-Line Testing (if initial workup negative)

• Mycoplasma genitalium NAAT if persistent urethritis/cervicitis with negative initial STI testing. 3
• Post-void residual volume if urinary retention suspected. 4
• Cystoscopy only if symptoms persist >1 month without identified cause, to evaluate for interstitial cystitis or structural abnormalities. 5

Management Based on Findings

If STI Testing Positive

• For Chlamydia: Azithromycin 1 g orally single dose OR Doxycycline 100 mg orally twice daily for 7 days. 1
• For Gonorrhea: Ceftriaxone 500 mg IM single dose (or 1 g if weight >150 kg). 1
• Treat sexual partners and advise abstinence until treatment completed. 3

If All Testing Negative (Non-Infectious Dysuria)

• Do NOT prescribe antibiotics, as this provides no benefit and increases resistance. 1
• Eliminate bladder irritants: discontinue caffeine, alcohol, acidic foods, and potential chemical irritants. 5
• Increase fluid intake to dilute urine and flush irritants. 5
• For postmenopausal women: consider vaginal estrogen therapy for atrophic changes. 5

If Symptoms Persist Despite Negative Workup

• Reassess in 48-72 hours: if dysuria persists despite adequate hydration, or if fever >37.8°C, frequency, urgency, or gross hematuria develop, repeat urinalysis and obtain urine culture. 1
• Consider imaging (renal/bladder ultrasound) if recurrent episodes to evaluate for anatomic abnormalities. 1
• Refer to urology if symptoms persist >1 month without identified cause for evaluation of interstitial cystitis or other chronic conditions. 5

Critical Pitfalls to Avoid

• Do not empirically treat with antibiotics for UTI based on symptoms alone when urinalysis is negative, as this contributes to antimicrobial resistance without benefit. 1, 2
• Do not dismiss STI possibility in older or married patients; sexual history must be obtained sensitively but thoroughly. 3
• Do not assume all dysuria is UTI; the positive predictive value of symptoms alone is poor, especially with negative urinalysis. 2
• Do not order urine culture if urinalysis is negative and patient is asymptomatic for systemic infection, as this leads to overtreatment of asymptomatic bacteriuria. 1
• Do not continue antibiotics "just to complete the course" if the diagnosis is wrong; discontinue immediately to avoid harm. 1

Patient Education and Follow-Up

• Educate that negative urinalysis makes bacterial UTI extremely unlikely and antibiotics are not indicated. 1, 2
• Instruct to return immediately if fever >37.8°C, gross hematuria, severe suprapubic pain, or inability to void develops. 1
• Schedule follow-up in 48-72 hours if symptoms do not improve with conservative measures. 1
• Advise sexual abstinence until STI testing results return if sexually active. 3