Antibiotic Treatment for Epididymitis
For sexually active men under 35 years, treat with ceftriaxone 250 mg IM once PLUS doxycycline 100 mg orally twice daily for 10 days; for men over 35 years or those with enteric organism risk factors, use ofloxacin 300 mg orally twice daily for 10 days OR levofloxacin 500 mg orally once daily for 10 days. 1
Age-Based Treatment Algorithm
Men Under 35 Years (Sexually Active)
The primary pathogens in this age group are N. gonorrhoeae and C. trachomatis, which cause the majority of sexually transmitted epididymitis 2. The recommended regimen is:
- Ceftriaxone 250 mg IM as a single dose
- PLUS Doxycycline 100 mg orally twice daily for 10 days 3, 1, 4
This dual therapy provides coverage for both gonococcal and chlamydial infections, preventing microbiologic cure failure, infertility, and chronic pain 3. The doxycycline component must be continued for the full 10-day course to adequately treat chlamydial infection 4.
Important caveat: If the patient practices insertive anal intercourse, enteric organisms are also likely pathogens 2. In this scenario, substitute levofloxacin 500 mg orally once daily for 10 days OR ofloxacin 300 mg orally twice daily for 10 days in place of doxycycline to provide broader enteric coverage 1, 5.
Men Over 35 Years or With Enteric Risk Factors
Epididymitis in this population is typically caused by enteric Gram-negative organisms (predominantly E. coli) secondary to urinary tract infection or bladder outlet obstruction 2, 6. The recommended regimen is:
- Ofloxacin 300 mg orally twice daily for 10 days 3, 1
- OR Levofloxacin 500 mg orally once daily for 10 days 1, 5
Fluoroquinolones alone provide adequate coverage for enteric pathogens without requiring additional gonococcal coverage 2. Studies demonstrate that cultured bacteria in antibiotic-naive patients show >85% susceptibility to fluoroquinolones 6.
Enteric risk factors include: age >35 years, not sexually active, recent urinary instrumentation, known urinary tract abnormalities, or positive urine dipstick for leukocytes and nitrites 1, 5.
Alternative Regimens for Allergies
For patients allergic to cephalosporins and/or tetracyclines who require sexually transmitted infection coverage, use ofloxacin 300 mg orally twice daily for 10 days as monotherapy 3. However, note that fluoroquinolone resistance in gonorrhea is increasing, making this a less optimal choice when gonococcal infection is suspected 5.
Adjunctive Therapy
All patients require:
- Bed rest until fever and local inflammation subside 3, 1
- Scrotal elevation 3, 1
- Analgesics for pain control 3, 1
These supportive measures are critical for symptom relief and should be continued until inflammation resolves 3.
Critical Follow-Up Parameters
Reevaluate within 3 days if no clinical improvement occurs 3, 1. Failure to improve requires reassessment of both diagnosis and antibiotic choice 3. The most important pitfall is missing testicular torsion, which presents with sudden severe pain and requires immediate surgical consultation 1. Torsion is more common in adolescents and occurs more frequently when inflammation or infection is absent 3.
Persistent swelling after completing antibiotics warrants comprehensive evaluation for: tumor, abscess, testicular infarction, testicular cancer, tuberculous epididymitis, or fungal epididymitis 3, 1. In immunosuppressed patients, fungi and mycobacteria are more likely causative organisms 3, 1.
Sexual Partner Management
Partners must be evaluated and treated if contact occurred within 60 days preceding symptom onset 3, 1. Patients should abstain from sexual intercourse until both they and their partners complete therapy and are symptom-free 3, 1. This prevents reinfection and transmission of sexually transmitted pathogens 3.
Diagnostic Testing Before Treatment
While empiric therapy should be initiated immediately, obtain the following tests 3, 1:
- Gram-stained smear of urethral exudate (≥5 polymorphonuclear leukocytes per oil immersion field indicates urethritis) 3, 1
- Nucleic acid amplification test for N. gonorrhoeae and C. trachomatis 3, 1
- First-void urine examination for leukocytes if urethral Gram stain is negative 3, 1
- Culture and Gram-stained smear of uncentrifuged urine 3
- Syphilis serology and HIV testing 3, 1
Modern molecular diagnostics identify causative pathogens in 88% of antibiotic-naive patients, with 16S rDNA analysis increasing detection rates by 10% 6. However, treatment should never be delayed waiting for results 3.
Special Populations
HIV-positive patients with uncomplicated epididymitis receive the same treatment regimens as HIV-negative patients 3, 1. However, maintain higher suspicion for fungal and mycobacterial causes in immunosuppressed individuals 3, 1.