How to treat a patient with a urinary tract infection (UTI) presenting with positive nitrates and white blood cells (WBCs) in the urine, but no growth on culture?

Treatment of UTI with Positive Nitrites and WBCs but No Growth on Culture

In a symptomatic patient with positive nitrites and WBCs on urinalysis but no growth on culture, you should treat empirically with antibiotics if the patient has specific urinary symptoms (dysuria, frequency, urgency, fever, or gross hematuria), as the combination of positive nitrites and leukocytes has 96% specificity for UTI, and culture-negative results often reflect technical issues rather than absence of infection. 1

Understanding the Diagnostic Dilemma

The scenario you describe represents a common clinical challenge where laboratory findings conflict:

• Positive nitrites have 98% specificity for bacterial UTI, making false positives extremely rare 1
• The combination of positive leukocyte esterase and nitrites achieves 93% sensitivity and 96% specificity for predicting culture positivity 2
• Culture-negative results with positive urinalysis can occur due to:
  • Specimen contamination (most common cause) 2
  • Insufficient bladder dwell time before collection 1
  • Prior antibiotic exposure 2
  • Fastidious organisms not detected by standard culture 3
  • Processing delays (>1 hour at room temperature or >4 hours refrigerated) 2

Treatment Algorithm

Step 1: Verify Clinical Symptoms

Treat if the patient has ANY of these specific urinary symptoms: 1, 2

• Dysuria (>90% accuracy for UTI when present) 2
• Urinary frequency or urgency
• Fever >37.8°C
• Gross hematuria
• Suprapubic pain

Do NOT treat if: 2

• Only non-specific symptoms present (confusion, functional decline in elderly)
• Patient is completely asymptomatic
• Only cloudy or malodorous urine without other symptoms

Step 2: Assess Specimen Quality

Consider the specimen contaminated if: 2

• High epithelial cell counts present
• Mixed bacterial flora reported
• Improper collection technique used

If contamination suspected, obtain a new specimen via: 2

• Midstream clean-catch in cooperative patients
• In-and-out catheterization in women unable to provide clean specimens
• Fresh catheter placement if indwelling catheter present 2

Step 3: Initiate Empiric Treatment for Symptomatic Patients

First-line empiric therapy (choose based on local resistance patterns): 1, 4

• Nitrofurantoin 100 mg PO twice daily for 5 days (preferred if negative leukocyte esterase) 5
• Trimethoprim-sulfamethoxazole DS (160/800 mg) PO twice daily for 3 days 6, 4
• Cephalexin 500 mg PO four times daily for 5 days 5

Key treatment principles: 1

• Short-course therapy (3-5 days) is recommended for uncomplicated UTIs
• Adapt dosing to patient's weight, renal clearance, and liver function
• Plan early re-evaluation based on clinical response

Step 4: Special Population Considerations

Elderly/Long-term care patients: 2

• Asymptomatic bacteriuria prevalence is 15-50% in this population
• Do NOT treat pyuria alone without specific urinary symptoms
• Confusion or falls alone do NOT justify UTI treatment

Catheterized patients: 2

• Asymptomatic bacteriuria and pyuria are nearly universal
• Only treat if fever, hypotension, or specific urinary symptoms present
• Replace catheter before collecting specimen if treating

Pediatric patients (<2 years with fever): 7

• Always obtain urine culture before antibiotics
• 10-50% of culture-proven UTIs have false-negative urinalysis
• Use catheterization or suprapubic aspiration for specimen collection

Common Pitfalls to Avoid

Do NOT: 2

• Treat asymptomatic bacteriuria (positive culture without symptoms) - this provides no clinical benefit and increases resistance
• Continue antibiotics beyond recommended duration (3-5 days for uncomplicated cystitis)
• Rely on cloudy or malodorous urine alone as indication for treatment in elderly patients
• Order urinalysis or culture in completely asymptomatic patients

Critical caveat: 2

• If strong clinical suspicion persists despite negative culture, collect a new properly-obtained specimen and request repeat culture before continuing antibiotics
• Consider non-urinary sources of infection in febrile patients with negative cultures

When to Reconsider the Diagnosis

Obtain repeat specimen and culture if: 2, 6

• Symptoms persist despite 48-72 hours of appropriate antibiotic therapy
• Patient develops systemic signs (fever >38.3°C, hypotension, rigors)
• Recurrent episodes occur (≥2 in 6 months or ≥3 in 12 months)

Consider alternative diagnoses if: 2

• Repeat culture remains negative with proper collection technique
• No response to empiric antibiotics
• Atypical symptoms present

The key principle is that positive nitrites with WBCs in a symptomatic patient warrants empiric treatment regardless of culture results, as the high specificity of this combination makes true infection highly likely, and culture-negative results often reflect technical rather than clinical issues. 1, 2