How to differentiate urethritis from urinary tract infection (UTI) in males with hematuria and leukocyturia?

Distinguishing Urethritis from UTI in Males with Hematuria and Leukocyturia

The key diagnostic distinction between urethritis and UTI in males with blood and leukocytes in urine is based on specific urethral discharge examination, Gram stain findings, and symptom patterns, with urethritis typically showing ≥5 WBCs per oil immersion field on urethral smear versus ≥10 WBCs per high-power field in urine for UTI. 1

Diagnostic Criteria

Urethritis Diagnosis

• Definitive diagnostic criteria:

  • Mucopurulent or purulent urethral discharge
  • Gram stain of urethral secretions showing ≥5 WBCs per oil immersion field (preferred rapid diagnostic test) 1
  • Positive leukocyte esterase test on first-void urine
  • Microscopic examination of first-void urine showing ≥10 WBCs per high-power field

• Characteristic findings:

  • Presence of urethral discharge (may be clear to purulent)
  • Urethral pruritus or discomfort
  • Dysuria (often described as burning at the tip of the penis)
  • Symptoms typically more pronounced in the morning 2
  • Absence of WBCs containing intracellular Gram-negative diplococci distinguishes non-gonococcal urethritis from gonococcal urethritis 1

UTI Diagnosis

• Definitive diagnostic criteria:

  • Positive leukocyte esterase AND nitrite test on urine dipstick (sensitivity 83.3%, specificity 89.8%) 3
  • Urine culture showing significant bacterial growth (typically ≥10³ CFU/mL in males)
  • Microscopic examination showing WBCs and bacteria in urine

• Characteristic findings:

  • Dysuria (often described as burning throughout urination)
  • Urinary frequency and urgency
  • Suprapubic pain or tenderness 4
  • Often associated with anatomical or functional abnormalities of the urinary tract in males 5

Key Differentiating Features

Clinical Presentation

1. Symptom Location:

   • Urethritis: Discomfort typically localized to the anterior urethra/meatus
   • UTI: Pain more diffuse, often with suprapubic discomfort

2. Discharge:

   • Urethritis: Urethral discharge is a hallmark feature
   • UTI: Discharge is uncommon; cloudy urine more typical

3. Associated Symptoms:

   • Urethritis: Rarely presents with fever or systemic symptoms
   • UTI: May present with fever, flank pain if upper tract involvement 4

Laboratory Findings

Parameter	Urethritis	UTI
Leukocyte location	Primarily in urethral secretions	Throughout urine specimen
Nitrite test	Usually negative	Often positive (indicates bacteria)
Flow cytometry threshold	Leukocytes ≥15/μL and bacteria ≥20/μL in first-void urine [6]	Higher bacterial counts throughout urine
Causative organisms	N. gonorrhoeae, C. trachomatis (15-55%), M. genitalium, T. vaginalis [1]	Primarily Enterobacteriaceae (80% of male UTIs) [5]

Diagnostic Algorithm

1. Initial Assessment:

   • Collect detailed sexual history (urethritis is typically sexually transmitted)
   • Assess for urinary tract abnormalities or recent instrumentation (suggests UTI) 1
   • Evaluate for discharge (strongly suggests urethritis)

2. First-line Testing:

   • Collect first-void urine for:
     • Leukocyte esterase and nitrite testing
     • Microscopy for WBCs and bacteria
     • PCR testing for N. gonorrhoeae, C. trachomatis, M. genitalium, and T. vaginalis

3. Confirmatory Testing:

   • If discharge present: Perform Gram stain of urethral secretions
   • If no discharge but suspicion for UTI: Collect midstream urine for culture

4. Interpretation:

   • Positive STI testing + urethral discharge = Urethritis
   • Negative STI testing + positive nitrite + positive urine culture = UTI
   • In cases with overlapping features, consider both diagnoses

Common Pitfalls and Caveats

1. Co-infection: UTI and urethritis can coexist, with a possible association between them 3. When in doubt, test for both conditions.

2. Asymptomatic urethritis: Inflammation may be present without symptoms; asymptomatic urethritis is less likely to have detectable pathogens than symptomatic cases 7.

3. False negatives: Avoid testing within 3 weeks after antibiotic treatment as this can lead to false-negative results 2.

4. Overreliance on dipstick: While convenient, dipstick testing alone is insufficient for definitive diagnosis; microscopy and culture/PCR testing are essential for confirmation.

5. Complicated UTI in males: Most UTIs in males are considered complicated and require urological evaluation due to the higher likelihood of underlying structural abnormalities 1.

By systematically applying these diagnostic criteria and understanding the key differences between these conditions, clinicians can accurately distinguish urethritis from UTI in males presenting with hematuria and leukocyturia.