What does a nitrite-negative urine sample with moderate leukocytes and a White Blood Cell (WBC) count of 21-50 indicate in a patient?

Nitrite-Negative Urine with Moderate Leukocytes and WBC 21-50

This urinalysis pattern indicates pyuria (inflammation in the urinary tract) but does NOT automatically mean a urinary tract infection requires treatment—the presence or absence of specific urinary symptoms is the critical determining factor for whether to proceed with further testing or treatment. 1

What This Result Pattern Means

The combination of findings suggests several possible scenarios:

• Pyuria is present (WBC 21-50 per high-power field exceeds the diagnostic threshold of ≥10 WBCs/HPF), which indicates inflammation in the genitourinary tract but has exceedingly low positive predictive value for actual infection 1

• Nitrite-negative results effectively exclude common gram-negative uropathogens like E. coli, Proteus, and Klebsiella in most cases, as these organisms convert urinary nitrate to nitrite 1, 2

• The sensitivity of nitrite testing is poor (19-48%) but specificity is excellent (92-100%), meaning negative nitrite results cannot rule out UTI, particularly in patients who void frequently or have insufficient bladder dwell time 1, 3

Clinical Decision Algorithm

Step 1: Assess for Specific Urinary Symptoms

If the patient has NO specific urinary symptoms (dysuria, frequency, urgency, fever >37.8°C, or gross hematuria):

• Do NOT order urine culture or initiate antibiotics—this represents asymptomatic bacteriuria with pyuria, which should not be treated 1, 4
• The Infectious Diseases Society of America explicitly recommends against treating asymptomatic bacteriuria even when pyuria is present (Grade A-II recommendation) 1
• This is particularly important in elderly patients, where pyuria has low predictive value due to 15-50% prevalence of asymptomatic bacteriuria 1

If the patient HAS specific urinary symptoms (dysuria, frequency, urgency, fever, or gross hematuria):

• Obtain a properly collected urine specimen for culture BEFORE starting antibiotics using midstream clean-catch or catheterization if contamination is suspected 1, 4
• The combination of pyuria (≥10 WBCs/HPF) AND acute urinary symptoms justifies proceeding to culture 1
• Process the specimen within 1 hour at room temperature or 4 hours if refrigerated 1

Step 2: Consider Alternative Causes of Nitrite-Negative Pyuria

Several organisms and conditions cause pyuria without positive nitrite:

• Non-nitrate-reducing organisms: Staphylococcus saprophyticus, Enterococcus, Candida, and some Pseudomonas species do not produce nitrite 1, 2
• Insufficient bladder dwell time: Frequent voiding (especially in young children and infants) prevents adequate nitrate-to-nitrite conversion, requiring at least 4 hours of bladder dwell time 3
• Dietary factors: Lack of dietary nitrate intake can result in false-negative nitrite despite true infection 2
• Specimen contamination: High epithelial cell counts indicate contamination and require repeat collection 1
• Non-infectious inflammation: Interstitial cystitis, urethritis from sexually transmitted infections, or genitourinary inflammation from other causes 1

Step 3: Special Population Considerations

Elderly or long-term care residents:

• Evaluate ONLY with acute onset of specific UTI symptoms—do not test or treat based on non-specific symptoms like confusion or functional decline alone 1, 4
• Asymptomatic bacteriuria prevalence is 15-50% in this population, making pyuria alone meaningless 1

Catheterized patients:

• Do NOT screen for or treat asymptomatic bacteriuria, as pyuria and bacteriuria are nearly universal with chronic catheterization 1, 3
• Reserve testing for symptomatic patients with fever, hypotension, or specific urinary symptoms 1

Febrile infants and children <2 years:

• ALWAYS obtain urine culture before antibiotics, as 10-50% of culture-proven UTIs have false-negative urinalysis 3
• Young infants have particularly poor nitrite sensitivity due to frequent voiding 3

Diagnostic Performance Data

• Leukocyte esterase alone: 83% sensitivity, 78% specificity for UTI 1, 4
• Combined leukocyte esterase OR nitrite: 93% sensitivity, 72% specificity 1, 3
• Both leukocyte esterase AND nitrite positive: 93% sensitivity, 96% specificity 1, 3
• Both leukocyte esterase AND nitrite negative: 88-95% negative predictive value, effectively ruling out UTI 1, 5

Critical Pitfalls to Avoid

• Never treat based on urinalysis alone without symptoms—this leads to unnecessary antibiotic use and resistance development 1, 4
• Never assume cloudy or malodorous urine indicates infection—these observations alone should not trigger treatment, especially in elderly patients 1
• Never delay culture collection if antibiotics are indicated—always obtain culture before starting treatment in symptomatic patients 1, 4
• Never ignore the possibility of contamination—if specimen quality is poor (high epithelial cells), repeat collection using proper technique 1

When to Proceed with Urine Culture

Obtain urine culture in these specific scenarios:

• Symptomatic patients with pyuria (≥10 WBCs/HPF or positive leukocyte esterase) AND specific urinary symptoms 1
• Suspected pyelonephritis or urosepsis with systemic signs (fever >38.3°C, hypotension, rigors) regardless of urinalysis results 1
• Febrile infants <2 years with any positive urinalysis component 3
• Recurrent UTIs requiring documentation and susceptibility testing 1