Which antibiotic regimen is recommended for acute epididymitis in sexually active men under 35 versus men over 35, and what alternatives are appropriate for patients with serious β‑lactam allergy?

Antibiotic Treatment for Epididymitis

For sexually active men under 35, give ceftriaxone 250 mg IM once plus doxycycline 100 mg orally twice daily for 10 days; for men 35 or older, use levofloxacin 500 mg once daily or ofloxacin 300 mg twice daily for 10 days. 1

Age-Based Treatment Algorithm

Men < 35 Years (Sexually Transmitted Pathogens)

The dominant organisms are Chlamydia trachomatis and Neisseria gonorrhoeae, requiring dual coverage 1:

• First-line regimen: Ceftriaxone 250 mg intramuscular (single dose) plus doxycycline 100 mg orally twice daily for 10 days 1, 2
• The ceftriaxone covers gonorrhea while doxycycline treats chlamydia 1
• Critical pitfall: Never use doxycycline alone—it fails to adequately cover gonorrhea 1

Special consideration for men who practice insertive anal intercourse:

• Use levofloxacin 500 mg once daily plus doxycycline 100 mg twice daily for 10 days to cover both sexually transmitted organisms and enteric pathogens simultaneously 1

Men ≥ 35 Years (Enteric Organisms)

The predominant pathogen is Escherichia coli and other gram-negative enteric bacteria, typically related to urinary tract abnormalities or instrumentation 1:

• First-line regimen: Levofloxacin 500 mg orally once daily for 10 days or ofloxacin 300 mg orally twice daily for 10 days 1, 2
• Fluoroquinolones achieve excellent tissue penetration into the epididymis and testis 1
• Critical pitfall: Do not use doxycycline alone in this age group—it fails to cover enteric pathogens and leads to treatment failure 1

Patients with Serious β-Lactam Allergy

For patients who cannot receive ceftriaxone (those < 35 years):

• Alternative regimen: Ofloxacin 300 mg orally twice daily for 10 days provides coverage of both gonorrhea and chlamydia 1
• Important caveat: Rising fluoroquinolone-resistant N. gonorrhoeae limits the desirability of this option 1
• A less-preferred macrolide alternative is azithromycin 500 mg on day 1, then 250 mg daily on days 2–5 1

Essential Diagnostic Steps Before Treatment

Before initiating antibiotics, perform these critical assessments:

• Immediately rule out testicular torsion—this is mandatory, especially in adolescents or when inflammatory signs are absent, because testicular viability declines after 4–6 hours 1, 3
• Obtain urethral Gram stain: ≥5 polymorphonuclear leukocytes per oil-immersion field confirms urethritis 1, 2
• Send nucleic acid amplification tests (NAAT) or cultures for N. gonorrhoeae and C. trachomatis 1, 2
• If urethral Gram stain is negative, examine first-void urine for leukocytes and send for culture 1, 2

Supportive Care and Monitoring

• Provide bed rest, scrotal elevation, and analgesics until fever and local inflammation resolve 1, 2
• Re-evaluate at 72 hours: Lack of clinical improvement mandates reassessment of diagnosis and therapy, potentially requiring surgical exploration 1, 2
• Monitor for progression to urosepsis (occurs in approximately 7% of severe cases) by checking vital signs, lactate, complete blood count, and blood cultures as needed 1

Management of Sexual Partners

• All sexual partners within 60 days preceding symptom onset must be evaluated and treated empirically 1, 3
• Both patient and partners must abstain from sexual activity until therapy is completed and both are asymptomatic 1, 3
• Failure to treat partners perpetuates reinfection cycles 3

Hospitalization Criteria

Admit patients with any of the following 1:

• Severe scrotal or testicular pain suggesting torsion, infarction, or abscess
• Fever ≥38°C
• Concerns about adherence to oral antimicrobial regimen

Special Populations

• HIV-infected or immunocompromised patients: Use the same initial antibiotic regimens as immunocompetent individuals 1, 2
• Maintain heightened suspicion for atypical organisms (fungi, mycobacteria) if standard therapy fails 1, 3

Key Contraindications

• Doxycycline is contraindicated in pregnancy; substitute azithromycin or amoxicillin in pregnant patients 1
• No clinically significant drug-drug interactions exist between levofloxacin and doxycycline when used together 1