Management of Acute Epididymitis
For sexually active men under 35 years, treat with ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days; for men 35 years and older, use levofloxacin 500 mg orally once daily for 10 days OR ofloxacin 300 mg orally twice daily for 10 days. 1
Age-Based Antibiotic Regimens
Men < 35 Years (Sexually Transmitted Etiology)
Ceftriaxone 250 mg intramuscularly as a single dose PLUS doxycycline 100 mg orally twice daily for 10 days is the first-line regimen to cover both Neisseria gonorrhoeae and Chlamydia trachomatis, which are the predominant pathogens in this age group 2, 1, 3.
This dual therapy is mandatory because monotherapy fails to provide adequate coverage for both organisms and risks treatment failure 1.
For men who practice insertive anal intercourse, enteric organisms such as Escherichia coli may also be causative, and the regimen should be modified to ceftriaxone 250 mg IM single dose PLUS levofloxacin 500 mg orally once daily for 10 days to cover both sexually transmitted and enteric pathogens 2, 3.
Men ≥ 35 Years (Enteric Organism Etiology)
Levofloxacin 500 mg orally once daily for 10 days OR ofloxacin 300 mg orally twice daily for 10 days is recommended to target gram-negative enteric bacteria, particularly E. coli, which predominate in this age group 2, 1, 4.
Enteric organisms are more common in older men due to bladder outlet obstruction from benign prostatic hyperplasia, urethral strictures, recent urinary instrumentation, or anatomical urinary tract abnormalities 2, 5.
Diagnostic Evaluation Before Treatment
Urethral Gram stain should be performed to detect urethritis (≥5 polymorphonuclear leukocytes per oil immersion field) and make a presumptive diagnosis of gonococcal infection 2, 1.
Nucleic acid amplification testing (NAAT) on intraurethral swab or first-void urine is essential to identify N. gonorrhoeae and C. trachomatis 2, 1.
First-void urine microscopy examining uncentrifuged urine for leukocytes (pyuria) is recommended when urethral Gram stain is negative 1.
Urine culture with antibiogram should be obtained before starting antibiotics to guide therapeutic adjustments if the patient fails to improve 1.
Serologic testing for syphilis and HIV counseling/testing should be offered as part of the comprehensive STI evaluation 1.
Supportive Measures
Bed rest, scrotal elevation, and scrotal support should be recommended until fever and local inflammation resolve 2, 1.
Analgesics and anti-inflammatory medications (NSAIDs) can be used to control pain and reduce inflammation 1.
Hospitalization should be considered when severe pain suggests alternative diagnoses (testicular torsion, infarction, abscess), when patients are febrile, or when compliance with oral therapy is questionable 2.
Follow-Up and Reassessment
Mandatory re-evaluation at 48-72 hours is essential to confirm clinical improvement, defined by reduction in pain, swelling, and tenderness 1.
If no improvement occurs within 3 days of appropriate antibiotic therapy, both the diagnosis and antimicrobial regimen must be reassessed 2, 1.
Persistent swelling or tenderness after completing treatment warrants investigation for complications including epididymal abscess, testicular infarction, tumor, tuberculosis, or fungal epididymitis 1.
Scrotal ultrasound with Doppler should be performed if the diagnosis is uncertain or if complications are suspected 1.
Partner Management
All sexual partners from the preceding 60 days must be notified, evaluated, and treated empirically for both N. gonorrhoeae and C. trachomatis, regardless of the pathogen identified in the index patient 1.
Partners should receive the same dual-therapy regimen (ceftriaxone plus doxycycline) to prevent reinfection and ongoing transmission 1.
Patients must abstain from sexual activity until both they and their partners have completed therapy and are symptom-free 1.
Critical Differential Diagnosis
Testicular torsion must be excluded immediately as it is a surgical emergency; sudden onset of severe pain, negative Prehn sign (no pain relief with scrotal elevation), and absence of urethritis or urinary symptoms suggest torsion rather than epididymitis 2, 1.
Emergency surgical consultation is required if the diagnosis is questionable, because testicular viability is compromised within 6-8 hours of torsion 2, 1.
Common Pitfalls to Avoid
Do not use monotherapy in men < 35 years—single-agent fluoroquinolones fail to cover both gonorrhea and chlamydia adequately 1.
Do not rely solely on urinalysis in younger sexually active men, as STI-related epididymitis frequently presents without significant pyuria; urethral swab testing is mandatory 1.
Do not attribute persistent pain to neuropathic causes without systematically excluding structural complications such as abscess, tumor, or chronic epididymitis 1.
Failure to obtain urine culture before antibiotics limits the ability to tailor therapy when initial treatment fails 1.