How do I differentiate epididymitis from acute bacterial prostatitis in a sexually active man under 35 versus a man over 35, and what are the first‑line treatment regimens for each?

Differentiating Epididymitis from Acute Bacterial Prostatitis

In sexually active men under 35, epididymitis presents with gradual unilateral scrotal pain and a palpably swollen, tender epididymis, while acute bacterial prostatitis presents with fever, perineal or suprapubic pain, and an exquisitely tender, boggy prostate on digital rectal examination—treat epididymitis with ceftriaxone 250 mg IM once plus doxycycline 100 mg orally twice daily for 10 days, and treat acute bacterial prostatitis with a fluoroquinolone (levofloxacin 500 mg daily) or trimethoprim-sulfamethoxazole for 2–4 weeks. 1, 2, 3

Clinical Presentation: Key Distinguishing Features

Epididymitis

• Gradual onset of unilateral posterior scrotal pain developing over hours to days, beginning at the lower pole of the epididymis and progressing upward 1, 2
• Palpable epididymal swelling and tenderness with the testis in normal anatomic position 1, 4
• Positive Prehn sign: pain relief when elevating the scrotum over the symphysis pubis (helps exclude testicular torsion) 2
• Scrotal erythema, warmth, and reactive hydrocele may develop as inflammation progresses 2
• Urethral discharge or dysuria may accompany sexually transmitted epididymitis in younger men 1, 2
• Fever is present only in severe cases 2

Acute Bacterial Prostatitis

• Acute onset of fever, chills, and systemic symptoms (rigors, myalgias, malaise) 1
• Perineal, suprapubic, or lower back pain—not scrotal pain 1
• Irritative voiding symptoms: dysuria, urinary frequency, urgency, hesitancy 1
• Digital rectal examination reveals an exquisitely tender, boggy, swollen prostate—this is the pathognomonic finding 1
• Avoid vigorous prostatic massage in acute prostatitis, as it may precipitate bacteremia 1

Age-Stratified Pathogen Profiles

Men < 35 Years (Sexually Active)

Epididymitis

• Primary pathogens: Chlamydia trachomatis and Neisseria gonorrhoeae 1, 2, 4
• These infections originate from urethral pathogens ascending via the vas deferens 2
• Pyuria may be absent in sexually transmitted epididymitis because the infection arises from urethritis, not the urinary tract 2

Acute Bacterial Prostatitis

• Escherichia coli and other Enterobacteriaceae remain the predominant pathogens even in younger men 1
• Sexually transmitted organisms (N. gonorrhoeae, C. trachomatis) rarely cause acute bacterial prostatitis 1

Men ≥ 35 Years

Epididymitis

• Primary pathogens: Enteric gram-negative bacteria, especially E. coli 1, 2, 5
• Associated with bladder outlet obstruction (benign prostatic hyperplasia), recent urinary instrumentation, or structural urinary abnormalities 1, 2, 5
• Pyuria is typically present because infection results from urinary reflux into the ejaculatory ducts 2

Acute Bacterial Prostatitis

• E. coli causes 80% of cases, followed by other Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus species 1
• Risk factors include recent urinary catheterization, transrectal prostate biopsy, or bladder outlet obstruction 1

Diagnostic Evaluation

For Suspected Epididymitis

Men < 35 Years

• Urethral Gram stain or intraurethral swab: ≥5 polymorphonuclear leukocytes per oil immersion field confirms urethritis 1, 2
• Nucleic acid amplification test (NAAT) on intraurethral swab or first-void urine for N. gonorrhoeae and C. trachomatis 1, 2
• First-void urine microscopy for leukocytes if urethral Gram stain is negative 1, 2
• Syphilis serology and HIV testing 1, 2
• Critical pitfall: Relying solely on urinalysis misses the majority of STI-related epididymitis cases, because these infections originate from urethral pathogens, not urinary bacteria 2

Men ≥ 35 Years

• Urinalysis with microscopy to detect pyuria (≥5 WBCs per high-power field) 2, 3
• Urine culture and Gram stain to identify enteric gram-negative organisms 1, 2
• Urethral swab only if urethritis symptoms (discharge, dysuria) are present 3

All Ages

• Exclude testicular torsion immediately—this is a surgical emergency requiring intervention within 4–6 hours 1, 2, 6
• Torsion presents with sudden onset of severe pain, negative Prehn sign, and absent cremasteric reflex 2
• Emergency Doppler ultrasound or surgical consultation is mandatory when torsion cannot be excluded clinically 1, 2

For Suspected Acute Bacterial Prostatitis

• Midstream urine culture (not expressed prostatic secretions in acute disease) yields the causative uropathogen 1
• Urinalysis shows pyuria and bacteriuria 1
• Blood cultures if the patient appears septic 1
• Avoid vigorous prostatic massage during acute infection to prevent bacteremia 1

First-Line Treatment Regimens

Epididymitis in Men < 35 Years (Sexually Transmitted)

• Ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days 1, 2, 3, 4, 5
• This dual regimen provides coverage for both N. gonorrhoeae and C. trachomatis 1, 2, 3
• Alternative if ceftriaxone unavailable: Cefixime 400 mg orally single dose plus doxycycline 100 mg orally twice daily for 10 days 3
• For men who practice insertive anal intercourse: Ceftriaxone 250 mg IM single dose PLUS levofloxacin 500 mg orally once daily for 10 days (to cover enteric organisms) 2, 3, 5

Epididymitis in Men ≥ 35 Years (Enteric Organisms)

• Levofloxacin 500 mg orally once daily for 10 days 1, 2, 3, 5
• Alternative: Ofloxacin 300 mg orally twice daily for 10 days 1, 2, 3, 5
• Fluoroquinolone monotherapy is sufficient because sexually transmitted pathogens are uncommon in this age group 2, 3
• Do not use ceftriaxone plus doxycycline in men ≥35 years unless there is clear evidence of sexually transmitted infection 3

Acute Bacterial Prostatitis (All Ages)

• Fluoroquinolone: Levofloxacin 500 mg orally once daily for 2–4 weeks (mild to moderate cases) 1
• Alternative: Trimethoprim-sulfamethoxazole 160/800 mg orally twice daily for 2–4 weeks 1
• For severe or septic patients: Hospitalize and initiate IV therapy with a fluoroquinolone, third-generation cephalosporin, or aminoglycoside plus ampicillin until afebrile for 24–48 hours, then transition to oral therapy to complete 4 weeks total 1
• Fluoroquinolones achieve excellent prostatic tissue penetration 1

Adjunctive Supportive Care

Epididymitis

• Bed rest, scrotal elevation, and analgesics until fever and local inflammation subside 1, 2, 3
• Scrotal support (athletic supporter) reduces edema 2
• NSAIDs for pain control 2

Acute Bacterial Prostatitis

• Analgesics and antipyretics 1
• Stool softeners to reduce pain during defecation 1
• Avoid urethral catheterization if possible; if urinary retention occurs, use suprapubic catheterization 1

Follow-Up and Management of Treatment Failure

Epididymitis

• Reassess within 3 days if no clinical improvement occurs 1, 2, 3
• Lack of improvement warrants re-evaluation of both diagnosis and therapy 1, 2, 3
• Persistent symptoms after completing antibiotics require comprehensive evaluation for tumor, abscess, testicular infarction, testicular cancer, tuberculous or fungal epididymitis 1, 2, 3
• Doppler ultrasound to exclude abscess or other complications 2

Acute Bacterial Prostatitis

• Clinical improvement (defervescence, reduced pain) should occur within 48–72 hours 1
• If no improvement, obtain urine culture with susceptibility testing and adjust antibiotics accordingly 1
• Failure to respond may indicate prostatic abscess, requiring imaging (transrectal ultrasound or CT) and possible drainage 1

Management of Sexual Partners (Epididymitis Only)

• Refer all sexual partners from the preceding 60 days for evaluation and empiric treatment if epididymitis is confirmed or suspected to be caused by N. gonorrhoeae or C. trachomatis 1, 2, 3
• Partners receive the same dual regimen (ceftriaxone plus doxycycline) regardless of the index patient's identified pathogen 2, 3
• Patients must abstain from sexual intercourse until they and all partners have completed therapy and are symptom-free 1, 2, 3

Special Populations

HIV-Infected Patients

• Treat uncomplicated epididymitis with the same regimens as HIV-negative patients 1, 3
• Consider fungal and mycobacterial causes more frequently in immunosuppressed patients 1, 3, 6
• Fungi (Blastomyces, Histoplasma, Coccidioides) and Mycobacterium tuberculosis can involve the epididymis or testis in immunocompromised hosts 1, 6

Men Who Have Sex with Men (Insertive Anal Intercourse)

• Enteric organisms (E. coli) are more likely even in men < 35 years 6, 5
• Use ceftriaxone 250 mg IM single dose PLUS levofloxacin 500 mg orally once daily for 10 days to cover both STI and enteric pathogens 2, 3, 5

Common Pitfalls to Avoid

Epididymitis

• Failing to exclude testicular torsion in all cases of acute scrotal pain—torsion is a surgical emergency requiring immediate intervention 1, 2, 6
• Using fluoroquinolone monotherapy in men < 35 years—this fails to adequately cover C. trachomatis and N. gonorrhoeae 2, 3
• Relying solely on urinalysis in young men—STI-related epididymitis often presents without pyuria because the infection originates from urethritis, not the urinary tract 2
• Not obtaining cultures before starting antibiotics—urine culture with susceptibility testing is crucial for tailoring therapy if the initial regimen fails 2, 3

Acute Bacterial Prostatitis

• Performing vigorous prostatic massage during acute infection—this can precipitate bacteremia and sepsis 1
• Using nitrofurantoin or fosfomycin—these agents achieve inadequate prostatic tissue penetration and are ineffective for prostatitis 2
• Inadequate treatment duration—acute bacterial prostatitis requires 2–4 weeks of antibiotics to prevent progression to chronic bacterial prostatitis 1