Initial Treatment of 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, use 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 Active)
The primary pathogens are Chlamydia trachomatis and Neisseria gonorrhoeae, which account for the majority of cases in this age group 1, 3, 4. The recommended regimen is:
- Ceftriaxone 250 mg IM as a single dose 1, 2, 5
- PLUS Doxycycline 100 mg orally twice daily for 10 days 1, 2, 5
This dual therapy provides coverage for both gonococcal and chlamydial infections, which frequently coexist and are often accompanied by asymptomatic urethritis 1, 3. The doxycycline component is critical as C. trachomatis epididymitis historically accounted for two-thirds of "idiopathic" cases and can lead to oligozoospermia if untreated 4.
Men Who Practice Insertive Anal Intercourse
These patients require coverage for enteric organisms in addition to STI pathogens 1, 2. The recommended regimen is:
- Ceftriaxone 250 mg IM as a single dose 2
- PLUS Levofloxacin 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice daily for 10 days 2
The fluoroquinolone component provides necessary coverage for E. coli and other enteric bacteria transmitted during anal intercourse 1.
Men Over 35 Years
Epididymitis in this age group is predominantly caused by enteric Gram-negative organisms, particularly E. coli, often associated with urinary tract abnormalities such as bladder outlet obstruction, benign prostatic hyperplasia, or prior urologic instrumentation 1, 3, 4. The recommended regimen is:
- Levofloxacin 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice daily for 10 days 1, 2
Fluoroquinolones alone are sufficient in this population as they provide excellent coverage for enteric pathogens 1, 3. However, a critical caveat: rising fluoroquinolone resistance in E. coli isolates means that treatment failure should prompt culture-directed therapy 6.
Essential Diagnostic Workup Before Treatment
Empiric therapy should be initiated immediately, but the following diagnostic tests guide partner management and confirm etiology 1, 2:
- Gram-stained smear of urethral exudate showing ≥5 polymorphonuclear leukocytes per oil immersion field confirms urethritis 1, 2
- Nucleic acid amplification test (NAAT) or culture for N. gonorrhoeae and C. trachomatis from urethral swab or first-void urine 1, 2
- First-void urine examination for leukocytes if urethral Gram stain is negative 1, 2
- Urine culture and Gram stain for enteric organisms, particularly in men over 35 1, 2
- Syphilis serology and HIV testing should be offered 1, 2
Adjunctive Therapy
All patients require supportive measures 1, 2:
- Bed rest until fever and inflammation subside 1, 2
- Scrotal elevation to reduce swelling 1, 2
- Analgesics for pain control 1, 2
Critical Follow-Up and Red Flags
Reevaluate within 3 days if no clinical improvement occurs 1, 2. Failure to improve requires reconsideration of the diagnosis and antimicrobial regimen 1, 2.
Persistent swelling and tenderness after completing therapy warrants comprehensive evaluation for 1, 2:
- Testicular cancer
- Abscess formation
- Testicular infarction
- Tuberculous or fungal epididymitis (especially in immunocompromised patients)
Testicular Torsion Must Be Excluded
Testicular torsion is a surgical emergency that must be ruled out in all cases, particularly in adolescents 1, 2. Emergency consultation is indicated when 1, 2:
- Pain onset is sudden and severe
- Initial examination does not confirm urethritis or urinary tract infection
- Patient lacks evidence of inflammation or infection
Torsion occurs more frequently in patients without signs of infection, and delayed diagnosis compromises testicular viability 1, 2.
Sexual Partner Management
Partners of patients with STI-related epididymitis must be evaluated and treated 1, 2. Contact tracing should include all partners within 60 days preceding symptom onset 1, 2. Patients should abstain from sexual intercourse until both they and their partners complete treatment and are symptom-free 1, 2.
Female partners of men with C. trachomatis epididymitis frequently have asymptomatic cervical infection or pelvic inflammatory disease and require treatment 4.
Special Populations
HIV-Infected Patients
HIV-positive patients with uncomplicated epididymitis receive the same treatment regimens as HIV-negative patients 1, 2. However, fungal and mycobacterial causes are more common in immunosuppressed individuals and should be considered if standard therapy fails 1, 2.
Hospitalization Criteria
Consider hospitalization when 1:
- Severe pain suggests alternative diagnoses (torsion, abscess, infarction)
- Patient is febrile
- Concerns exist about treatment compliance
Common Pitfalls to Avoid
Do not use fluoroquinolones as monotherapy in men under 35 unless enteric organisms are confirmed, as this misses chlamydial infection which requires 10 days of treatment 1, 3.
Do not assume age alone determines etiology: STIs were found in 14% of cases across all age groups in contemporary studies, not just in younger men 7.
Do not overlook the 10-day treatment duration: shorter courses are inadequate for preventing complications such as infertility and chronic pain 1, 5, 3.