What is the likely diagnosis and appropriate treatment for a female adult patient of childbearing age presenting with large leukocytes, moderate hematuria, and a nitrite negative urine test result?

Likely Diagnosis and Management

This presentation of large leukocytes with moderate hematuria and negative nitrite in a woman of childbearing age most likely represents an acute uncomplicated urinary tract infection (UTI), and you should obtain a urine culture and initiate empiric antibiotic therapy immediately if she has accompanying urinary symptoms (dysuria, frequency, urgency, or fever). 1, 2

Diagnostic Interpretation

The combination of positive leukocyte esterase with negative nitrite does NOT rule out UTI—in fact, this pattern is common and still warrants treatment when symptoms are present. 1, 3

• Leukocyte esterase sensitivity is 83% with specificity of 78%, meaning it reliably detects pyuria but can have false positives from contamination or non-infectious inflammation. 4, 2

• Nitrite has poor sensitivity (only 19-53%) but excellent specificity (92-100%) for UTI. 4, 2 A negative nitrite test has little value in ruling out infection because:

  • Many uropathogens don't produce nitrite (including Staphylococcus saprophyticus, common in young women, and Enterococcus species). 4, 5
  • Frequent voiding prevents the 4-hour bladder dwell time needed for bacteria to convert dietary nitrates to nitrites. 4
  • Low dietary nitrate intake can cause false-negative results. 5

• The moderate hematuria supports UTI diagnosis, as gross or microscopic hematuria is a recognized UTI-associated symptom. 1, 2

• When nitrite is negative but leukocyte esterase is positive, the positive predictive value for UTI is 79% with sensitivity of 82% in symptomatic patients. 3

Critical Clinical Decision Point

You must determine if the patient has specific urinary symptoms before proceeding with treatment. 1, 2

If Symptomatic (dysuria, frequency, urgency, fever >38.3°C, suprapubic pain):

1. Obtain urine culture with antimicrobial susceptibility testing BEFORE starting antibiotics—this is mandatory for proper antimicrobial stewardship. 1, 2

2. Initiate empiric antibiotic therapy immediately after culture collection:

   • First-line: Nitrofurantoin 100 mg four times daily for 5 days (preferred for uncomplicated cystitis). 1, 2
   • Alternative: Fosfomycin 3g single dose or Trimethoprim-sulfamethoxazole DS twice daily for 3 days (if local resistance <20%). 1
   • Avoid fluoroquinolones as first-line due to resistance concerns and adverse effects. 1, 3

3. Re-evaluate at 48-72 hours and adjust antibiotics based on culture results and clinical response. 1

If Asymptomatic (no dysuria, frequency, urgency, fever, or suprapubic pain):

Do NOT treat—this likely represents asymptomatic bacteriuria, which should not be treated in non-pregnant women of childbearing age. 2, 6 Treatment provides no clinical benefit and only increases antimicrobial resistance and adverse drug effects. 2, 6

Special Considerations for Women of Childbearing Age

• If pregnant or pregnancy cannot be ruled out: Always obtain culture and treat even asymptomatic bacteriuria due to 20-40% risk of progression to pyelonephritis. 1 Avoid fluoroquinolones entirely and avoid nitrofurantoin near term (>36 weeks). 1

• Consider Staphylococcus saprophyticus infection, which is common in sexually active young women, produces negative nitrite results, and is typically sensitive to nitrofurantoin and TMP-SMX. 3, 7

• If recurrent UTIs (≥2 in 6 months or ≥3 in 12 months): Document each episode with culture to guide targeted therapy and consider prophylactic strategies. 1, 2

Common Pitfalls to Avoid

• Do not assume negative nitrite rules out UTI—approximately 50% of culture-positive UTIs have negative nitrite results, especially with non-E. coli organisms. 3, 5

• Do not treat based on urinalysis alone without symptoms—pyuria has exceedingly low positive predictive value in asymptomatic patients (10-50% of women have asymptomatic bacteriuria). 2, 6

• Ensure proper specimen collection (midstream clean-catch) to avoid contamination, which causes false-positive leukocyte esterase results. 4, 2 High epithelial cell counts indicate contamination. 2

• Do not delay culture collection—always obtain culture before antibiotics in symptomatic patients with significant pyuria. 1, 2

Expected Organisms and Antibiotic Sensitivities

• E. coli causes 75-85% of uncomplicated UTIs in young women and is typically sensitive to nitrofurantoin (>95%), cefazolin (>94%), and cefuroxime (>98%). 3, 7

• Non-E. coli organisms (including S. saprophyticus, Klebsiella, Proteus, Enterococcus) are more common with negative nitrite results and may show better sensitivity to TMP-SMX. 3, 7

• Trimethoprim resistance has reached 20-23% in some regions, making it less reliable as first-line therapy. 3