What is the recommended treatment for epididymo-orchitis in men greater than 35 years old?

Treatment of Epididymo-Orchitis in Men Over 35 Years

For men greater than 35 years old with epididymo-orchitis, treat with fluoroquinolone monotherapy: either levofloxacin 500 mg orally once daily for 10 days OR ofloxacin 300 mg orally twice daily for 10 days. 1, 2, 3

Rationale for Age-Based Treatment

Pathogen Differences by Age

• In men over 35 years, Gram-negative enteric bacteria (particularly E. coli) are the predominant pathogens causing epididymitis, occurring in the context of urinary tract infections rather than sexually transmitted infections 1, 3
• This contrasts sharply with men under 35 years, where Chlamydia trachomatis and Neisseria gonorrhoeae are the primary causative organisms 1
• The shift in pathogen etiology at age 35 is well-established across CDC guidelines from 1993 through 2025 1, 2, 3

Associated Risk Factors in Older Men

• Nonsexually transmitted epididymitis in men over 35 is strongly associated with urinary tract abnormalities including recent urinary tract instrumentation or surgery, anatomical abnormalities of the genitourinary tract, and bladder outlet obstruction from benign prostatic hyperplasia 1, 3
• These underlying urologic conditions facilitate bacterial reflux of urine into the ejaculatory ducts, which is the mechanism of infection in this age group 4

Recommended Treatment Regimen

First-Line Antibiotic Options

• Levofloxacin 500 mg orally once daily for 10 days 1, 2, 3
• Ofloxacin 300 mg orally twice daily for 10 days 1, 3, 4

Both fluoroquinolones provide excellent tissue penetration into the epididymis and testis, which is essential for adequate treatment 5

Important Caveat About Fluoroquinolone Resistance

• Rising ciprofloxacin resistance in E. coli isolates in Europe and the USA creates concern about fluoroquinolone efficacy 5
• If the patient fails to improve within 3 days of appropriate fluoroquinolone therapy, obtain urine culture results and adjust antibiotics based on sensitivity patterns 2, 3
• Consider alternative antimicrobials with adequate genital tissue penetration if fluoroquinolone resistance is documented 5

Essential Diagnostic Workup

Required Testing

• Urinalysis and urine culture with Gram stain are essential to identify enteric pathogens in men over 35 3, 4
• Urine culture should be obtained before starting antibiotics to guide therapeutic adjustments if necessary 2
• In one ED study, only 62.1% of men diagnosed with epididymo-orchitis received a urine culture, representing a significant gap in appropriate care 6

When STI Testing Is NOT Indicated

• Men over 35 years do NOT routinely require testing for Chlamydia or Neisseria gonorrhoeae unless they are sexually active with new or multiple partners 1, 3
• The CDC guidelines clearly distinguish that enteric organisms, not STIs, are the expected pathogens in this age group 1, 3

Adjunctive Management

Supportive Measures

• Bed rest and scrotal elevation until fever and local inflammation subside 1, 3
• NSAIDs for pain control 3
• Scrotal supporter to reduce edema 2

Follow-Up and Re-Evaluation

• Re-evaluate at 48-72 hours to confirm clinical improvement 2
• If no improvement occurs within 3 days of appropriate treatment, re-evaluate both diagnosis and therapy 2, 3
• Consider alternative diagnoses including testicular abscess, testicular cancer, or tuberculous epididymitis if symptoms persist 3
• Doppler ultrasound should be considered if the diagnosis is uncertain or to rule out complications 3

Hospitalization Criteria

• Severe pain suggesting alternative diagnoses (testicular torsion, testicular infarction, or abscess) 1, 3
• Fever or systemic signs of infection 1, 3
• Concern for patient noncompliance with oral antimicrobial regimen 1

Common Pitfalls to Avoid

• Do NOT use the STI regimen (ceftriaxone plus doxycycline) in men over 35 years unless there is specific evidence of sexually transmitted infection 1, 3
• Do NOT rely solely on urinalysis without culture, as culture and sensitivity results are critical for guiding therapy in this population 2, 3
• Do NOT use nitrofurantoin or fosfomycin for epididymitis treatment due to inadequate tissue penetration into the epididymis and testis 2
• Failure to arrange urological follow-up for men over 50 years is a documented gap in care, as these patients require evaluation for underlying urologic abnormalities 7