How should I treat epididymitis in a sexually active man under 35 versus an older man, including first‑line antibiotics, supportive care, and follow‑up?

Treatment of 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 over 35, give levofloxacin 500 mg orally once daily for 10 days OR ofloxacin 300 mg orally twice daily for 10 days. 1, 2

Age-Based Treatment Algorithm

Men Under 35 Years (Sexually Transmitted Etiology)

The pathogen profile in this age group is dominated by sexually transmitted organisms—primarily Chlamydia trachomatis and Neisseria gonorrhoeae—which require dual antibiotic coverage. 2, 3

First-line regimen:

• Ceftriaxone 250 mg intramuscularly as a single dose 1, 2, 4
• PLUS doxycycline 100 mg orally twice daily for 10 days 1, 2, 4

This combination targets both gonorrhea (via ceftriaxone) and chlamydia (via doxycycline), which are the predominant pathogens in sexually active young men. 2, 5

Special consideration for men who practice insertive anal intercourse:

• Use ceftriaxone 250 mg IM once PLUS levofloxacin 500 mg orally once daily for 10 days (or ofloxacin 300 mg orally twice daily for 10 days) instead of doxycycline, as enteric organisms are more likely in this population. 3

Men Over 35 Years (Enteric Organism Etiology)

In older men, epididymitis is typically caused by enteric Gram-negative bacteria (especially E. coli) that ascend retrograde from the urinary tract, often in the setting of bladder outlet obstruction or anatomic abnormalities. 1, 2, 6

First-line regimen (choose one):

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

Fluoroquinolones provide excellent coverage against enteric pathogens and achieve high tissue concentrations in the epididymis. 1, 5

Alternative option:

• Ciprofloxacin 500 mg orally twice daily for 10 days is also effective against enteric organisms. 1

Supportive Care Measures

All patients require adjunctive management regardless of age:

• Bed rest with scrotal elevation using a rolled towel or supportive underwear until fever and local inflammation subside 1, 2, 4
• Analgesics for pain control during the acute phase 1, 2
• Complete sexual abstinence until both patient and partner(s) complete treatment and are symptom-free 1, 2, 4

Partner Management and Sexual Health

For men under 35 with sexually transmitted epididymitis:

• All sexual partners from the preceding 60 days must be evaluated and treated, even if asymptomatic 1, 2, 4
• HIV testing and syphilis screening are recommended as part of the evaluation, since sexually transmitted epididymitis indicates risk for other infections 1, 4
• Testing for gonorrhea and chlamydia through urine nucleic acid amplification tests or urethral swabs should be performed 1, 4

Follow-Up and Red Flags

Expected Timeline

• Improvement should occur within 3 days of starting antibiotics 2, 4
• If no improvement within 3 days, reevaluate both the diagnosis and treatment regimen 1, 2, 4

Warning Signs Requiring Immediate Action

Seek emergency evaluation immediately if:

• Sudden, severe pain develops—this may indicate testicular torsion, a surgical emergency that can cause permanent testicular damage if not corrected within hours 1, 2, 4
• The cremasteric reflex is absent or pain onset was abrupt, as these findings suggest torsion rather than epididymitis 5

Return for reevaluation if:

• Pain, swelling, or fever persist beyond 3 days of appropriate antibiotic therapy 1, 2
• Palpable masses or persistent swelling remain after completing antibiotics—this requires comprehensive evaluation for tumor, abscess, infarction, testicular cancer, or tuberculous/fungal epididymitis 1, 2, 4

Critical Pitfalls to Avoid

• Never assume improvement means cure—the full 10-day antibiotic course must be completed to prevent chronic complications, infertility, and chronic scrotal pain 1, 3
• Do not confuse epididymitis with testicular torsion—torsion presents with sudden onset of severe pain and requires immediate surgical intervention, whereas epididymitis has gradual onset 2, 5
• Do not resume sexual activity prematurely, as this spreads infection to partners and can worsen the condition 1, 4
• Do not overlook urologic abnormalities in older men—bladder outlet obstruction or anatomic abnormalities are common underlying causes that may require urologic evaluation 6, 3

Special Populations

HIV-positive patients:

• Receive the same treatment regimen as HIV-negative patients for uncomplicated epididymitis 2, 4
• However, immunosuppressed individuals are at higher risk for fungal or mycobacterial causes, which require different diagnostic approaches and treatments 1, 4

Hospitalization considerations:

• Admit patients with severe pain suggesting alternative diagnoses, high fever, or likely non-compliance with oral therapy 2