What does a urinalysis showing negative leukocyte (white blood cell) esterase but positive for nitrites indicate?

Interpreting a Urinalysis with Negative Leukocyte Esterase but Positive Nitrites

A urinalysis showing negative leukocyte esterase but positive nitrites most likely indicates the presence of asymptomatic bacteriuria rather than a true urinary tract infection (UTI), as the absence of pyuria (indicated by negative leukocyte esterase) suggests lack of inflammatory response despite bacterial presence. 1

Understanding the Significance of Urinalysis Components

Nitrite Test

• Mechanism: Indicates the presence of bacteria that convert dietary nitrates to nitrites in the urine
• Characteristics:
  • High specificity (98%, range 90-100%) but lower sensitivity (53%, range 15-82%) 1
  • Highly specific with few false positives - when positive, strongly suggests bacterial presence
  • Requires approximately 4 hours of bladder incubation time for conversion to occur
  • Not all urinary pathogens reduce nitrate to nitrite (particularly Enterococcus) 2

Leukocyte Esterase Test

• Mechanism: Surrogate marker for pyuria (white blood cells in urine)
• Characteristics:
  • Moderate sensitivity (83%, range 67-94%) and specificity (78%, range 64-92%) 1
  • Absence of leukocyte esterase in bacteriuria is valuable for distinguishing asymptomatic bacteriuria from true UTI 1

Clinical Interpretation of Negative LE/Positive Nitrite Pattern

Most Likely Explanations:

1. Asymptomatic bacteriuria: The key distinction between asymptomatic bacteriuria and true UTI is the presence of pyuria 1

   • Common in school-aged and older girls (can occur in infancy as well)
   • Studies suggest antimicrobial treatment may do more harm than good in asymptomatic bacteriuria 1

2. Early/developing infection: Bacterial presence detected before significant inflammatory response

3. Technical factors:

   • Improper specimen collection or handling
   • Delayed testing of specimen (leukocyte esterase may degrade over time)

Diagnostic Approach

1. Correlate with clinical presentation:

   • In asymptomatic patients: Consider asymptomatic bacteriuria
   • In symptomatic patients: Consider early infection or false negative leukocyte esterase

2. Confirm with urine culture:

   • Urinalysis cannot substitute for urine culture to definitively diagnose UTI 1
   • The AAP guideline recommends both urinalysis suggesting infection AND ≥50,000 CFU/mL of a uropathogen to establish UTI diagnosis 1

3. Microscopic examination:

   • Consider microscopic analysis for WBCs and bacteria
   • Enhanced urinalysis (counting chamber assessment of pyuria with Gram staining) has greater sensitivity and specificity than standard urinalysis 1

Common Pitfalls to Avoid

1. Overdiagnosis of UTI:

   • Treating asymptomatic bacteriuria as UTI can lead to unnecessary antibiotic use
   • False positive nitrites can occur in approximately 2% of cases 3

2. Underdiagnosis of UTI:

   • Relying solely on leukocyte esterase for screening (combined tests have higher sensitivity)
   • In a study of adults, the combined sensitivity of nitrite and leukocyte esterase tests was 94% 4

3. Specimen collection issues:

   • Contaminated specimens can lead to false positive results
   • Even with ideal collection techniques, abnormal urinalysis results are common in disease-free women 3

4. Antibiotic selection based on nitrite status:

   • The absence of nitrite should not affect routine empiric antibiotic choice 2
   • Only about 3% of nitrite-negative UTIs are caused by Enterococcus (which doesn't produce nitrite) 2

Bottom Line for Clinical Practice

When encountering a urinalysis with negative leukocyte esterase but positive nitrites:

• Consider asymptomatic bacteriuria as the most likely explanation
• Confirm with urine culture before initiating treatment
• In asymptomatic patients, treatment is generally not recommended
• In symptomatic patients, consider other clinical factors and the possibility of early infection
• Remember that the nitrite test alone has limited sensitivity (53%) but high specificity (98%) 1