Management of Moderate Leukocytes with Negative Nitrites in Pregnant Women
Obtain a urine culture immediately before initiating any antibiotics, as the combination of moderate leukocytes and negative nitrites creates diagnostic uncertainty that requires definitive microbiological confirmation. 1
Diagnostic Interpretation
The finding of moderate leukocytes with negative nitrites presents a diagnostic challenge in pregnancy:
- The nitrite test has poor sensitivity (53%) for detecting urinary tract infections, meaning a negative result does not rule out infection, while leukocyte esterase testing has 83% sensitivity but only 78% specificity 1
- Pregnancy causes physiologic leukocytosis, with a 36% increase in the upper reference limit for total WBC and a 55% increase in neutrophils, which can complicate interpretation of both urinary and systemic leukocyte findings 1, 2
- Pyuria (white blood cells in urine) is the key distinguishing feature: true UTI is characterized by bacteriuria + pyuria + symptoms, whereas asymptomatic bacteriuria presents with bacteriuria but minimal pyuria 1
Management Algorithm
Step 1: Assess Clinical Context
- Determine gestational age for appropriate risk stratification, as management considerations differ by trimester 1
- Evaluate for symptoms: dysuria, frequency, urgency, suprapubic pain, fever, or flank pain indicating pyelonephritis 1
- Distinguish between urinary leukocytes versus systemic leukocytosis: if the concern is elevated blood WBC count rather than urinary findings, investigate for infection only if counts exceed 20×10⁹/L, as pregnancy-induced leukocytosis is physiologic 1, 2
Step 2: Obtain Definitive Diagnosis
- Collect a clean-catch midstream or catheterized urine specimen to minimize contamination 1
- Process the specimen within 1 hour at room temperature or 4 hours if refrigerated to ensure accurate culture results 1
- Send for urine culture before starting antibiotics, as this provides the definitive diagnosis and guides subsequent therapy 1
Step 3: Treatment Decision
If symptomatic:
- Initiate empirical antibiotic therapy while awaiting culture results to prevent maternal and fetal complications, including pyelonephritis, preterm labor, and low birth weight 1
If asymptomatic:
- Wait for culture results before treating, as asymptomatic bacteriuria treatment may cause more harm than benefit in some cases 1
- Note that gram-positive organisms (group B streptococci, enterococci) may produce negative nitrite tests even with significant bacteriuria, as these organisms do not reduce nitrates to nitrites 3
Critical Pitfalls to Avoid
- Do not rely on dipstick testing alone: the combination of nitrite and leukocyte esterase tests has 92% sensitivity and 95% specificity when used together, but neither test alone is sufficient to rule out infection 3
- Do not dismiss negative nitrites: 43% of culture-proven UTIs in pregnant women have negative nitrite tests, particularly with gram-positive organisms 3
- Do not attribute all leukocytosis to infection: pregnancy itself causes marked physiologic increases in WBC that remain stable between 8-40 weeks gestation and further elevate after delivery, resolving to pre-pregnancy levels by day 21 postpartum 2
- Do not delay culture collection: obtaining culture after antibiotic initiation significantly reduces diagnostic yield and may lead to inappropriate or prolonged antibiotic therapy 1
Special Considerations
- The upper reference limit for total WBC in pregnancy is 15.0×10⁹/L (compared to 11.0×10⁹/L in non-pregnant adults), driven primarily by neutrophilia 2
- Postpartum leukocytosis is expected: WBC counts elevate significantly from the first day after birth (regardless of delivery mode) and resolve to pre-delivery levels by day 7 on average 2
- If systemic leukocytosis exceeds 20×10⁹/L and persists, investigate for infection, inflammatory conditions, or rarely, hematologic malignancy, though pregnancy-induced leukocytosis can occasionally reach these levels 1, 4