Orchitis Drug of Choice
For sexually active men under 35 years, the drug of choice is ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days to cover both gonococcal and chlamydial infections. 1, 2
Age-Based Treatment Algorithm
Men Under 35 Years (Sexually Transmitted Pathogens)
Ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days is the first-line regimen because sexually transmitted infections (Chlamydia trachomatis and Neisseria gonorrhoeae) are the predominant causes in this age group. 1, 2
The 2024 European guideline has increased the ceftriaxone dose to 1 g IM single dose alongside doxycycline, reflecting evolving resistance patterns. 3
For patients with cephalosporin or tetracycline allergy, alternative regimens include ofloxacin 300 mg orally twice daily for 10 days OR levofloxacin 500 mg orally once daily for 10 days. 2
The FDA-approved doxycycline dosing for acute epididymo-orchitis caused by C. trachomatis or N. gonorrhoeae is 100 mg orally twice daily for at least 10 days. 4
Men Over 35 Years (Enteric Organisms)
Ofloxacin 300 mg orally twice daily for 10 days OR levofloxacin 500 mg orally once daily for 10 days is the first-line regimen because enteric gram-negative bacilli (especially E. coli) are the most common pathogens in this age group. 1, 2
These patients often have underlying urologic abnormalities such as benign prostatic hyperplasia or bladder outlet obstruction that predispose to infection. 5, 6
Rising fluoroquinolone resistance in E. coli isolates is an emerging concern, necessitating culture-guided therapy adjustments if patients fail to improve. 6
Mixed Risk Factors (Both STI and Enteric Pathogens)
- Ceftriaxone 1 g IM single dose PLUS either ofloxacin or levofloxacin provides dual coverage when the clinical history suggests both sexually transmitted and enteric pathogen risks. 3
Essential Diagnostic Steps Before Treatment
Obtain nucleic acid amplification testing (NAAT) on first-void urine or urethral swab for C. trachomatis and N. gonorrhoeae in men under 35 years, as these organisms often do not grow on routine urine culture. 2, 5
Perform urethral Gram stain to detect >5 polymorphonuclear leukocytes per oil-immersion field as evidence of urethritis, even when systemic inflammatory markers are normal. 5
Order urine culture in men ≥35 years to identify enteric uropathogens; E. coli is the most common bacteria isolated. 5, 7
Obtain color-Doppler scrotal ultrasound immediately to confirm hyperemia (≈100% sensitivity for epididymo-orchitis) and exclude testicular torsion, which shows absent or markedly reduced flow and requires emergency surgery within 4-6 hours. 5
Critical Pitfall: Do Not Delay Treatment
Start empiric antibiotics immediately without awaiting culture results or inflammatory marker elevation, as sexually transmitted infections and early enteric infections frequently present with normal CRP, ESR, or leukocyte counts. 5
Only 50% of men diagnosed with epididymo-orchitis in emergency departments are tested for gonorrhea and chlamydia, yet 13.8% of those tested are positive—highlighting the importance of routine STI screening. 7
Supportive Measures
Bed rest, scrotal elevation, and analgesics should be continued until fever and local inflammation subside. 1, 2
Hospitalization is warranted when severe pain suggests alternative diagnoses (testicular torsion, abscess, tumor), the patient is febrile, or non-compliance with oral antimicrobials is anticipated. 1
Follow-Up and Treatment Failure
Re-evaluate at 48-72 hours; failure to improve mandates reconsideration of alternative diagnoses including testicular tumor, abscess, infarction, tuberculosis, or fungal epididymitis. 1, 5
Persistent symptoms after completing antimicrobial therapy require comprehensive evaluation with imaging and tumor marker assessment. 2
Special Populations
Immunocompromised Patients
Fungal (Candida, Blastomyces, Histoplasma, Coccidioides) and mycobacterial (Mycobacterium tuberculosis) pathogens are more likely in HIV-positive or otherwise immunosuppressed individuals and may produce minimal systemic inflammatory response. 5
Tissue cultures for fungi and mycobacteria require specific media and prolonged incubation; communicate special handling instructions to the laboratory. 5
Fluconazole is the agent of choice for Candida epididymo-orchitis. 1
Viral Orchitis
Mumps virus is the most common viral cause and typically shows normal or only mildly raised inflammatory markers; diagnosis relies on IgM serology or acute and convalescent IgG serology. 5, 8
Other viral causes include Coxsackie virus, rubella virus, Epstein-Barr virus, and varicella-zoster virus. 1, 5
Treatment is supportive only (analgesics, scrotal elevation, rest) as antibiotics are ineffective for viral pathogens. 1