In a symptomatic adult with a urinalysis that is nitrite‑negative but leukocyte esterase‑positive, should I treat for a urinary tract infection?

Should You Treat for UTI with Negative Nitrites but Positive Leukocytes?

In a symptomatic adult with dysuria, frequency, or urgency, you should treat empirically for UTI when leukocyte esterase is positive even if nitrites are negative, because nitrites have poor sensitivity (19-48%) and miss nearly half of all culture-proven infections. 1

Understanding the Diagnostic Performance

The nitrite test is highly specific (92-100%) but has terrible sensitivity (19-48%), meaning a negative result does not rule out infection. 1 In contrast, leukocyte esterase achieves 83% sensitivity when used alone, and when you combine either positive leukocyte esterase or positive nitrite, sensitivity jumps to 93% with 72% specificity. 1

The key insight: Nitrites require 4-6 hours of bladder dwell time for bacteria to convert dietary nitrates, so patients who void frequently—especially young women, children, and anyone with urgency symptoms—will have false-negative nitrites despite active infection. 1

The Critical Decision Algorithm

Step 1: Confirm Both Requirements Are Met

You need both of these before treating:

• Acute urinary symptoms: dysuria, frequency, urgency, fever >38.3°C, or gross hematuria 1
• Pyuria: ≥10 WBCs/HPF on microscopy or positive leukocyte esterase 1

If the patient lacks specific urinary symptoms, stop here—this is asymptomatic bacteriuria and should not be treated regardless of urinalysis findings. 1

Step 2: Interpret the Leukocyte-Positive, Nitrite-Negative Result

This pattern is common and does NOT exclude UTI. The most likely scenarios are:

• Gram-positive organisms (Enterococcus, Staphylococcus saprophyticus) that don't produce nitrite reductase 2
• Frequent voiding preventing adequate bladder dwell time 1
• Early infection before sufficient bacterial load to generate detectable nitrite 1
• Dilute urine reducing nitrite concentration below detection threshold 2

Step 3: Empiric Treatment Decision

For uncomplicated cystitis in a symptomatic patient with positive leukocyte esterase:

• Start nitrofurantoin 100 mg orally twice daily for 5-7 days as first-line therapy 1
• Alternative: Fosfomycin 3 grams orally as a single dose 1
• Second alternative: Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days only if local resistance is <20% and no recent exposure 1

Obtain a urine culture before starting antibiotics if:

• Suspected pyelonephritis (fever, flank pain, costovertebral angle tenderness) 1
• Recurrent UTIs requiring documentation of each episode 1
• Pregnancy 1
• Recent antibiotic exposure 1
• Complicated UTI (catheter, structural abnormality, immunosuppression) 1

Common Pitfalls to Avoid

Never assume negative nitrites rule out infection. Studies show that 10-50% of culture-proven UTIs in febrile infants have completely normal urinalysis, and nitrite sensitivity is particularly poor in populations with frequent voiding. 1

Do not wait for culture results to start treatment in uncomplicated cystitis. The combination of symptoms plus positive leukocyte esterase has 93% sensitivity for culture-positive infection when either leukocyte esterase or nitrite is positive. 1

Never treat based on leukocytes alone without symptoms. Pyuria occurs in 15-50% of elderly patients and long-term care residents as asymptomatic bacteriuria, and treating it provides no benefit while promoting resistance. 1

Do not order urinalysis in asymptomatic patients. Non-specific symptoms like confusion or falls in the elderly do not justify UTI testing without acute dysuria, frequency, urgency, fever, or hematuria. 1

Special Population Modifications

Elderly/long-term care residents: Only treat when acute-onset specific urinary symptoms are present—confusion or functional decline alone are insufficient. 1 The presence of pyuria has particularly low predictive value in this population due to 15-50% prevalence of asymptomatic bacteriuria. 1

Catheterized patients: Do not screen for or treat asymptomatic bacteriuria; reserve testing for fever, hypotension, rigors, or suspected urosepsis. 1 Replace the catheter before collecting specimens if it has been in place ≥2 weeks. 1

Pregnant women: Always obtain culture before treatment, and treat asymptomatic bacteriuria to prevent pyelonephritis and adverse pregnancy outcomes. 1

Febrile infants <2 years: Always obtain both urinalysis and culture before antibiotics, as 10-50% of culture-proven UTIs have false-negative urinalysis. 1

When to Reassess

Reassess clinical response within 48-72 hours. 1 If symptoms persist or worsen, obtain imaging (ultrasound or CT) to exclude obstruction, stones, or other complications. 1 No routine follow-up culture is needed for uncomplicated cystitis that responds to therapy. 1