How do I treat a urinary analysis (UA) showing leukocytes but a negative nitrite test?

Management of Urinalysis with Leukocytes but Negative Nitrite

Treatment should only be initiated for symptomatic patients with leukocytes but negative nitrite on urinalysis, as this finding alone does not warrant antibiotic therapy in asymptomatic individuals. 1

Diagnostic Interpretation

• A urinalysis showing leukocytes (pyuria) but negative nitrite is not sufficient to diagnose a urinary tract infection (UTI) without accompanying symptoms 1
• The absence of pyuria (negative leukocyte esterase and no WBCs on microscopy) has excellent negative predictive value (approaching 100%) and can effectively rule out UTI 1
• Nitrite testing has high specificity (92-100%) but low sensitivity (19-48%), meaning a negative nitrite test does not exclude infection 1, 2
• Leukocyte esterase has higher sensitivity (72-97%) but lower specificity (41-86%) for UTI detection 1, 3

Management Algorithm

Step 1: Assess for Symptoms

• Treat only if symptomatic with:
  • Acute onset of dysuria, frequency, urgency, gross hematuria 1
  • Fever, costovertebral angle tenderness, suprapubic pain 1
  • In elderly: new/worsening urinary incontinence or suspected bacteremia 1

Step 2: Evaluate Need for Urine Culture

• If symptomatic with positive leukocyte esterase (even with negative nitrite), obtain urine culture before starting antibiotics 1
• If asymptomatic, regardless of leukocyte status, do not perform urine culture 1

Step 3: Treatment Decision

• Symptomatic patients with pyuria:
  • Initiate empiric antibiotics while awaiting culture results 1, 4
  • Choose antibiotics effective against common uropathogens (E. coli, Klebsiella, Enterobacter) 4
• Asymptomatic patients with pyuria:
  • Do not treat, even in elderly patients 1
  • Monitor for development of symptoms 1

Special Populations

Elderly Patients

• Avoid treating based on non-specific symptoms (confusion, fatigue, anorexia) without specific urinary symptoms 1
• Asymptomatic bacteriuria is common (10-50%) in long-term care facility residents and does not require treatment 1
• The absence of both leukocyte esterase and nitrite on dipstick effectively excludes UTI even in elderly patients 1

Catheterized Patients

• Bacteriuria and pyuria are nearly universal in long-term catheterized patients 1
• Only treat if signs of systemic infection are present (fever, rigors, hypotension) 1
• Change long-term catheters before collecting specimens and starting antibiotics 1

Common Pitfalls to Avoid

• Treating asymptomatic bacteriuria leads to unnecessary antibiotic use and resistance 1
• Relying solely on dipstick results without considering clinical symptoms leads to overtreatment 1, 5
• Assuming negative nitrite means the infection is caused by Enterococcus (this is rare, only ~3% of nitrite-negative UTIs) 6
• Treating non-specific symptoms in elderly patients as UTI without clear urinary symptoms 1

When to Consider Urology Referral

• Recurrent UTIs (≥3 episodes in 12 months) despite appropriate treatment 1
• Persistent symptoms despite appropriate antibiotic therapy 1
• Anatomic abnormalities suspected on imaging 1
• Complicated UTIs with systemic symptoms not responding to initial therapy 1