In an adult male presenting with acute unilateral scrotal pain, swelling, fever and a positive Prehn’s sign, what is the diagnosis and the appropriate first‑line antibiotic regimen based on his age (<35 versus ≥35 years)?

Epididymitis: Diagnosis and Age-Based Antibiotic Management

In an adult male presenting with acute unilateral scrotal pain, swelling, fever, and a positive Prehn's sign, the diagnosis is acute epididymitis, and first-line antibiotic therapy depends critically on age: men <35 years require ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days to cover sexually transmitted pathogens (Chlamydia trachomatis and Neisseria gonorrhoeae), while men ≥35 years should receive a fluoroquinolone such as levofloxacin 500 mg orally once daily for 10 days to target enteric organisms. 1, 2

Clinical Presentation Confirming Epididymitis

The clinical picture described—unilateral scrotal pain with swelling, fever, and positive Prehn's sign (pain relief with scrotal elevation)—is classic for acute epididymitis rather than testicular torsion. 3, 4

Key distinguishing features include:

• Gradual onset of posterior scrotal pain over hours to days (versus sudden onset in torsion) 1, 3, 2
• Positive Prehn's sign: Pain improves when elevating the scrotum over the symphysis pubis, differentiating epididymitis from torsion 3, 5
• Palpable epididymal swelling and tenderness, typically beginning at the lower pole and progressing upward 1, 3, 4
• Fever and systemic symptoms are common in bacterial epididymitis 3, 4

Critical pitfall: Always exclude testicular torsion first, as it is a surgical emergency requiring intervention within 6–8 hours. 6, 5 If onset is sudden, pain is severe, or diagnosis is uncertain, obtain immediate Doppler ultrasound and urological consultation. 1, 6

Diagnostic Evaluation Before Treatment

Before initiating empiric antibiotics, obtain the following studies to guide therapy and confirm diagnosis:

For Men <35 Years (Sexually Active)

• Urethral Gram stain or intraurethral swab for urethritis (≥5 polymorphonuclear leukocytes per oil immersion field) and presumptive gonococcal infection 1
• Nucleic acid amplification test (NAAT) on intraurethral swab or first-void urine for N. gonorrhoeae and C. trachomatis 1, 3
• First-void urinalysis for leukocytes if urethral Gram stain is negative 1
• Syphilis serology and HIV counseling/testing 1

Important caveat: In sexually active men <35 years, urinalysis may be normal or show minimal pyuria because the infection originates from urethral pathogens (Chlamydia, Gonorrhea) rather than urinary tract bacteria. 3, 4 Do NOT rely solely on urinalysis—urethral swab testing is essential. 3

For Men ≥35 Years

• Urine culture and Gram stain of uncentrifuged urine for enteric organisms (primarily E. coli) 1, 3
• Urinalysis examining first-void urine for pyuria 1, 3
• Evaluate for urinary tract abnormalities, recent instrumentation, or bladder outlet obstruction 1, 2

When to Use Doppler Ultrasound

• Diagnosis is uncertain or testicular torsion cannot be excluded clinically 3, 5
• No improvement after 3 days of appropriate antibiotic therapy 1
• Severe pain or systemic illness suggesting abscess or complications 3, 5

Ultrasound findings in epididymitis include enlarged epididymis with increased blood flow on color Doppler, scrotal wall thickening, and possible reactive hydrocele. 6, 3

Age-Based Antibiotic Regimens

Men <35 Years (Sexually Active)

Recommended regimen for sexually transmitted epididymitis:

• Ceftriaxone 250 mg IM single dose 1, 3, 2 PLUS
• Doxycycline 100 mg orally twice daily for 10 days 1, 3, 2

Rationale: This combination covers both N. gonorrhoeae (ceftriaxone) and C. trachomatis (doxycycline), the most common pathogens in this age group. 1, 4, 2 Chlamydia is found in approximately 48% of men <35 years with epididymitis, and gonococcal infection is also common. 7

Alternative for men who practice insertive anal intercourse (enteric organisms also likely):

• Ceftriaxone 250 mg IM single dose 2 PLUS
• Levofloxacin 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice daily for 10 days 2

This regimen provides broader coverage for enteric organisms (E. coli) in addition to sexually transmitted pathogens. 2

Men ≥35 Years

Recommended regimen for enteric organism-associated epididymitis:

• Levofloxacin 500 mg orally once daily for 10 days 3, 2 OR
• Ofloxacin 300 mg orally twice daily for 10 days 1, 2

Rationale: In men ≥35 years, epididymitis is usually caused by Gram-negative enteric bacteria (primarily E. coli) transported by reflux of urine into the ejaculatory ducts, often secondary to bladder outlet obstruction. 1, 2 Fluoroquinolones provide excellent tissue penetration and coverage for these organisms. 3, 8

For severe disease requiring hospitalization:

• Aminoglycoside PLUS cephalosporin IV initially 8
• Transition to oral fluoroquinolone (levofloxacin or ofloxacin) once improved 8

Do NOT use: Nitrofurantoin or fosfomycin—these agents have inadequate tissue penetration for epididymal infections. 3

Adjunctive Therapy and Follow-Up

Supportive Measures (All Patients)

• Bed rest until fever and local inflammation subside 1
• Scrotal elevation and use of scrotal supporter to reduce edema 1, 3
• Analgesics (NSAIDs preferred for anti-inflammatory effect) 1, 3

Follow-Up Timeline

• Re-evaluate at 48–72 hours to confirm clinical improvement 3
• Failure to improve within 3 days requires reassessment of both diagnosis and therapy 1, 3
• Consider alternative diagnoses: testicular torsion (if initially missed), tumor, abscess, testicular infarction, testicular cancer, tuberculous or fungal epididymitis 1, 3

Management of Sexual Partners (Men <35 Years)

• Refer all sexual partners for evaluation and treatment if contact occurred within 60 days preceding symptom onset 1
• Instruct patient to avoid sexual intercourse until both patient and partner(s) complete therapy and are asymptomatic 1

Common Pitfalls and How to Avoid Them

1. Missing testicular torsion: Always maintain high suspicion if onset is sudden or pain is severe, even if some features suggest epididymitis. Negative Prehn's sign (no pain relief with elevation) strongly suggests torsion. 6, 5 When in doubt, obtain immediate Doppler ultrasound and surgical consultation. 1, 6

2. Relying solely on urinalysis in young men: In sexually active men <35 years, urinalysis may be normal because STI-related epididymitis originates from urethral pathogens, not urinary tract bacteria. 3 Always obtain urethral swab or NAAT testing. 3

3. Using wrong antibiotic regimen for age group: Do NOT use fluoroquinolones alone in men <35 years—this misses Chlamydia coverage. 3, 2 Conversely, do NOT use ceftriaxone/doxycycline in men ≥35 years without STI risk factors—this provides inadequate enteric organism coverage. 1, 2

4. Inadequate treatment duration: Current tests for C. trachomatis are not sufficiently sensitive to exclude infection even when negative. 3 Complete the full 10-day course of doxycycline in younger men. 1, 2

5. Failing to reassess if no improvement: If pain does not begin to improve within 3 days of appropriate antibiotics, the diagnosis or pathogen may be wrong. 1, 3 Obtain ultrasound and consider alternative diagnoses or resistant organisms. 1, 3