What is the likely diagnosis and treatment for a patient with urethral discharge, fever, and dysuria (painful urination) without a history of sexual activity?

Urethral Discharge with Fever and Dysuria Without Sexual History

This presentation most likely represents a complicated urinary tract infection (UTI) with urethritis, and empiric treatment should include coverage for both typical urinary pathogens and atypical organisms with intravenous third-generation cephalosporin plus an aminoglycoside, given the presence of systemic symptoms (fever). 1

Diagnostic Considerations

Primary Differential Diagnosis

The combination of urethral discharge, fever, and dysuria without sexual history creates a diagnostic challenge that requires distinguishing between:

• Complicated UTI with urethritis - The presence of fever indicates systemic involvement, classifying this as a complicated UTI rather than simple urethritis 1
• Non-sexually transmitted urethritis - While urethritis is commonly sexually transmitted, noninfectious causes and atypical organisms can occur without sexual contact 1
• Ascending infection/pyelonephritis - Fever with dysuria raises concern for upper tract involvement 1

Critical Clinical Assessment

Immediate evaluation must determine the severity of systemic involvement:

• Assess for urosepsis using quick SOFA (qSOFA) criteria: respiratory rate ≥22/min, altered mental status, or systolic blood pressure ≤100 mmHg 1
• Examine for costovertebral angle tenderness to evaluate for pyelonephritis (positive likelihood ratio 1.7) 2
• Check for flank pain which increases probability of complicated UTI (positive likelihood ratio 1.6) 2

Diagnostic Testing Required

Obtain the following before initiating treatment:

• Urine culture is mandatory - This is a complicated UTI due to systemic symptoms (fever), requiring culture to guide targeted therapy 1
• Urethral swab for Gram stain - Can differentiate gonococcal from non-gonococcal urethritis and identify polymorphonuclear leukocytes (≥5 per oil immersion field diagnostic for urethritis) 1, 3
• Blood cultures (two sets) - Required when fever is present to rule out bacteremia/urosepsis 1
• Nucleic acid amplification tests - For Chlamydia trachomatis, Mycoplasma genitalium, and Ureaplasma urealyticum, even without sexual history 1, 3

Treatment Algorithm

Empiric Antibiotic Therapy

For complicated UTI with systemic symptoms (fever), initiate immediately: 1

• Intravenous third-generation cephalosporin (e.g., ceftriaxone 1-2g IV daily) as monotherapy, OR
• Combination therapy: Amoxicillin plus aminoglycoside, OR second-generation cephalosporin plus aminoglycoside 1

Important caveat: Do NOT use ciprofloxacin empirically if the patient has used fluoroquinolones in the last 6 months or if local resistance rates exceed 10% 1

Urethritis-Specific Coverage

If urethritis is prominent and sexually transmitted causes cannot be excluded despite negative sexual history:

• Add doxycycline 100 mg orally twice daily for 7 days to cover Chlamydia and other non-gonococcal urethritis pathogens 1
• Alternative: Erythromycin base 500 mg orally 4 times daily for 7 days if doxycycline contraindicated 1

Duration and Adjustment

• Continue empiric therapy until culture results available, then adjust based on susceptibilities 1
• Manage any urological abnormality identified during workup (strong recommendation) 1
• Replace or remove any indwelling catheter if present before starting antimicrobials 1

Common Pitfalls to Avoid

Critical errors that worsen outcomes:

• Treating as simple urethritis without addressing fever - Fever indicates complicated infection requiring broader coverage and IV therapy 1
• Assuming no sexually transmitted infection based solely on patient-reported sexual history - Asymptomatic infections are common, and patients may not disclose complete sexual history 1, 3
• Failing to obtain urine culture before antibiotics - This is the most common error in complicated UTI management 1
• Using fluoroquinolones empirically in urology patients - Resistance rates are typically >10% in this population 1

Etiology in Non-Sexually Active Patients

Possible causative organisms without sexual transmission: 1, 4, 5

• E. coli and other coliforms - Most common urinary pathogens causing ascending infection with urethritis
• Ureaplasma urealyticum - Can cause non-gonococcal urethritis without sexual transmission (U. parvum is not considered pathogenic) 1
• Herpes simplex virus - Occasionally causes urethritis without sexual contact 3
• Adenovirus - Less common viral cause 3
• Noninfectious causes - Trauma, foreign body, dermatologic conditions, or interstitial cystitis 6

Follow-Up Strategy

Re-evaluate if symptoms persist or worsen:

• If no improvement within 48-72 hours - Review culture results and adjust antibiotics based on susceptibilities 1
• If symptoms recur within 2 weeks - Repeat urine culture and antimicrobial susceptibility testing, assume resistance to initial agent 1
• Consider imaging (ultrasound or CT) if fever persists despite appropriate antibiotics to identify obstruction, abscess, or anatomic abnormality 1