Empiric Antibiotic Regimens for Epididymo-Orchitis
For sexually active men under 35 years, give ceftriaxone 250 mg intramuscularly as a single dose plus doxycycline 100 mg orally twice daily for 10 days; for men 35 years or older, or those with urinary tract instrumentation, prostatitis, or diabetes, 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 < 35 Years (Sexually Transmitted Etiology)
Ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days is the first-line regimen because Chlamydia trachomatis and Neisseria gonorrhoeae are the predominant pathogens in this age group. 1, 2, 3
Ceftriaxone covers gonorrhea while doxycycline targets chlamydia; doxycycline alone is insufficient because it does not adequately treat N. gonorrhoeae. 1
This dual therapy achieves microbiologic cure and prevents complications including infertility and chronic scrotal pain. 4, 5
The 10-day duration is critical—patients must complete the entire course even if symptoms improve earlier. 1, 2
Men ≥ 35 Years or With Urologic Risk Factors
Levofloxacin 500 mg orally once daily for 10 days OR ofloxacin 300 mg orally twice daily for 10 days is first-line therapy because enteric gram-negative organisms, predominantly Escherichia coli, cause infection in this population. 1, 2, 6
Fluoroquinolones achieve excellent tissue penetration into the epididymis and testis, making them ideal for treating enteric pathogens. 1, 5
Risk factors that mandate this regimen include age ≥ 35 years, recent urinary tract instrumentation or surgery, anatomical urinary tract abnormalities, benign prostatic hyperplasia, urethral stricture, and diabetes mellitus. 1, 7
Do NOT use doxycycline alone in men ≥ 35 years—it fails to cover enteric organisms and leads to treatment failure. 1, 6
Special Population: Men Who Practice Insertive Anal Intercourse
Levofloxacin 500 mg once daily PLUS doxycycline 100 mg twice daily for 10 days is recommended because both sexually transmitted pathogens (C. trachomatis, N. gonorrhoeae) and enteric organisms must be covered simultaneously in this population. 1, 5
This combination provides additive antimicrobial coverage with no clinically significant drug-drug interactions. 1
Diagnostic Priorities Before Initiating Therapy
Immediately exclude testicular torsion, especially in adolescents or patients with sudden-onset severe pain lacking inflammatory signs—surgical consultation is mandatory because testicular viability declines after 4–6 hours. 1, 2
Perform a urethral Gram stain: ≥ 5 polymorphonuclear leukocytes per oil-immersion field confirms urethritis and supports sexually transmitted etiology. 4, 1, 2
Obtain nucleic acid amplification testing (NAAT) or culture for N. gonorrhoeae and C. trachomatis on urethral swab or first-void urine. 4, 1, 2
If urethral Gram stain is negative, examine first-void urine for leukocytes and send for culture to detect urinary tract involvement. 4, 1, 2
Order syphilis serology and offer HIV testing because sexually transmitted epididymo-orchitis indicates risk for other infections. 4, 2
Hospitalization Criteria
Admit patients with severe scrotal or testicular pain suggesting alternative diagnoses (testicular torsion, infarction, abscess). 4, 1, 2
Admit febrile patients (temperature ≥ 38°C) for close monitoring and possible intravenous therapy. 4, 1, 2
Consider admission when adherence to oral antibiotics is uncertain to ensure completion of therapy. 4, 1, 2
Supportive Care and Monitoring
Prescribe bed rest with scrotal elevation (using rolled towel or supportive underwear) and analgesics until fever and local inflammation resolve. 1, 2, 6
Re-evaluate at 72 hours: lack of clinical improvement mandates reassessment of diagnosis and therapy, and may require surgical exploration. 1, 2, 6
Monitor for progression to urosepsis (occurs in approximately 7% of severe genitourinary infections) by checking vital signs, lactate, complete blood count, and obtaining blood cultures as needed. 1
Sexual Partner Management
All sexual partners within 60 days preceding symptom onset must be evaluated and treated empirically for sexually transmitted infections. 1, 2
Patients and partners must abstain from sexual activity until both have completed therapy and are asymptomatic. 1, 2
Alternative Regimens for Allergy or Resistance
For patients allergic to cephalosporins or tetracyclines (including those < 35 years), ofloxacin 300 mg twice daily for 10 days can cover both gonorrhea and chlamydia, though rising fluoroquinolone-resistant N. gonorrhoeae limits its desirability. 1
Ciprofloxacin 500 mg orally twice daily for 10 days is an alternative for men ≥ 35 years, though rising ciprofloxacin resistance in E. coli isolates in Europe and the USA necessitates caution. 2, 7
Critical Pitfalls to Avoid
Never delay empiric therapy while awaiting culture results—treatment must be started promptly based on age and risk factors. 1, 6
Never use monotherapy with doxycycline in men < 35 years because it does not cover gonorrhea. 1
Never use doxycycline in men ≥ 35 years because it fails to cover enteric pathogens. 1, 6
Never assume cure when pain improves—the full 10-day course is required to prevent chronic complications. 2
Systemic antibiotics are mandatory; topical agents alone are ineffective. 1