How should acute epididymitis be treated in an adult male, with antibiotic selection based on age and risk factors?

Treatment of Acute Epididymitis

Antibiotic selection for acute epididymitis must be based on patient age, with men under 35 years receiving ceftriaxone 1 g IM/IV plus doxycycline 100 mg twice daily for 10 days to cover sexually transmitted pathogens, while men 35 years and older should receive levofloxacin 500 mg daily for 10 days to target enteric organisms. 1, 2

Age-Based Treatment Algorithm

Men Under 35 Years (Sexually Active)

Primary pathogens: Chlamydia trachomatis and Neisseria gonorrhoeae are responsible for the majority of cases in this age group, with up to 90% caused by pathogen migration from the urethra. 1, 2

First-line therapy:

• Ceftriaxone 1 g IM or IV single dose PLUS doxycycline 100 mg orally twice daily for 10 days 1, 2, 3
• This dual therapy is essential because it covers both gonococcal and chlamydial infections simultaneously 2, 4

Alternative regimens (cephalosporin allergy):

• Gentamicin 240 mg IM single dose plus azithromycin 2 g orally single dose 1
• Levofloxacin 500 mg daily for 10 days OR ofloxacin 300 mg twice daily for 10 days 2, 3

Special consideration for men who practice insertive anal intercourse:

• Use ceftriaxone 1 g IM/IV single dose PLUS levofloxacin 500 mg daily for 10 days to cover both STI pathogens and enteric organisms 4

Men 35 Years and Older

Primary pathogens: Enteric gram-negative bacteria, predominantly Escherichia coli, typically associated with bladder outlet obstruction, benign prostatic hyperplasia, or recent urinary instrumentation. 1, 2, 3

First-line therapy:

• Levofloxacin 500 mg orally once daily for 10 days 2, 3, 4
• Alternative: Ofloxacin 300 mg orally twice daily for 10 days 2, 3

Critical point: The ceftriaxone plus doxycycline regimen is NOT appropriate for this age group because it targets STI pathogens rather than enteric organisms. 3

Essential Diagnostic Evaluation Before Treatment

Do not delay antibiotics while awaiting results, but obtain:

For Men Under 35 Years:

• Urethral Gram stain (≥5 polymorphonuclear leukocytes per oil immersion field indicates urethritis) 2, 3
• Nucleic acid amplification test (NAAT) for N. gonorrhoeae and C. trachomatis from intraurethral swab or first-void urine 2, 3
• First-void urine examination for leukocytes if urethral Gram stain is negative 2, 3
• Syphilis serology and HIV testing 3

For Men 35 Years and Older:

• Urinalysis with microscopy (looking for pyuria: ≥5 WBCs per high-power field) 3
• Urine culture and Gram stain to identify gram-negative organisms 2, 3
• Urethral swab only if urethritis symptoms are present 3

Important caveat: Recent research using 16S rDNA analysis demonstrates that a bacterial pathogen can be identified in 88% of antibiotic-naive patients, with E. coli accounting for 56% of cases. 5 However, STIs were found in 14% of cases across all age groups, not just younger men, challenging the strict age-based paradigm. 5

Adjunctive Supportive Measures

All patients should receive:

• Bed rest until fever and local inflammation subside 2, 3
• Scrotal elevation (relieves pain via Prehn sign) 2
• Analgesics for pain control 2, 3

Critical Differential Diagnosis: Testicular Torsion

Testicular torsion is a surgical emergency that MUST be excluded immediately, especially when: 2, 3

• Pain onset is sudden and severe (rather than gradual over hours to days) 2
• Prehn sign is negative (no pain relief with scrotal elevation) 2
• Patient is an adolescent or young adult 3
• No clinical evidence of urethritis or urinary tract infection is present 3

Emergency surgical consultation is mandatory if diagnosis is uncertain, as testicular viability is compromised within 6-8 hours. 2

Follow-Up and Management of Treatment Failure

Reassess within 3 days if no clinical improvement occurs: 2, 3

• Pain should begin to improve within 3 days of appropriate antibiotic therapy 2
• Lack of improvement warrants re-evaluation of both diagnosis and antibiotic choice 2, 3

If symptoms persist after completing the 10-day antibiotic course, perform comprehensive evaluation for: 2, 3

• Testicular tumor or cancer 2, 3
• Epididymal abscess 2, 3
• Testicular infarction 3
• Tuberculous or fungal epididymitis (especially in immunosuppressed patients) 3
• Fournier's gangrene (if systemic illness, scrotal skin changes, or crepitus present) 1

Management of Sexual Partners

For STI-related epididymitis: 3

• Refer all sexual partners from the preceding 60 days for evaluation and treatment 3
• Patient must abstain from sexual intercourse until both patient and all partners complete therapy and are symptom-free 3

Common Prescribing Errors to Avoid

Do not use ciprofloxacin as first-line therapy in men under 35 years because it has inadequate activity against C. trachomatis; levofloxacin or ofloxacin are the appropriate fluoroquinolones if needed. 3

Do not use nitrofurantoin or oral fosfomycin for epididymitis due to inadequate tissue penetration into the epididymis. 2

Do not assume all cases require antibiotics without proper diagnostic evaluation, though empirical therapy should not be delayed while awaiting results. 2, 6

Beware of rising fluoroquinolone resistance: Recent data show that in antibiotic-pretreated patients, bacterial susceptibility to fluoroquinolones drops to only 42%, compared to >85% in antibiotic-naive patients. 5, 7 This underscores the importance of obtaining cultures before initiating therapy.

Special Populations

HIV-positive patients: Receive the same treatment regimens as HIV-negative patients for uncomplicated epididymitis. 3

Immunosuppressed patients: Fungi and mycobacteria are more likely causative agents and should be considered if standard therapy fails. 3

Elderly men with bladder outlet obstruction: Investigate underlying urologic abnormalities (BPH, urethral stricture) and obtain history of recent instrumentation, as these are common predisposing factors. 3, 4