What's the next step in workup for a patient with elevated white blood cell (WBC) count and neutrophils on complete blood count (CBC) but normal chest X-ray, urinalysis, and stool exam?

Workup of Isolated Neutrophilic Leukocytosis

Obtain a manual differential count immediately to calculate absolute band count and assess for left shift, as these are the most powerful predictors of occult bacterial infection even when initial common sources are negative. 1, 2

Immediate Laboratory Assessment

Manual differential is mandatory - automated analyzers miss critical findings:

• Calculate absolute band count: if ≥1,500 cells/mm³, this carries the highest likelihood ratio (14.5) for documented bacterial infection 1, 2
• Assess for left shift (≥16% band neutrophils): likelihood ratio of 4.7 for bacterial infection, even with normal total WBC 1, 2
• Neutrophil percentage >90% has likelihood ratio of 7.5 for bacterial infection 1

Blood cultures should be obtained if any signs of systemic infection are present, including fever, hypotension, tachycardia, or altered mental status 2

Critical Clinical Re-Assessment

Systematically evaluate for occult infection sources that may not have been initially apparent:

Vital signs assessment:

• Fever >38°C or hypothermia <36°C 2
• Hypotension <90 mmHg systolic 2
• Tachycardia or tachypnea 2

Focused physical examination for occult sources:

• Skin/soft tissue: Examine for erythema, warmth, purulent drainage, cellulitis, or abscess formation 2
• Abdominal examination: Assess for peritoneal signs, tenderness, or organomegaly suggesting intra-abdominal infection 1, 2
• Respiratory: Evaluate for cough, dyspnea, chest pain, or focal findings suggesting pneumonia 2
• Musculoskeletal: Check for joint effusions, bone tenderness suggesting osteomyelitis or septic arthritis 1

Additional Diagnostic Testing

Serum lactate level: If >3 mmol/L, indicates severe sepsis requiring immediate intervention 2

Consider diagnostic paracentesis in patients with cirrhosis and ascites to rule out spontaneous bacterial peritonitis (neutrophil count >250 cells/mm³ in ascitic fluid indicates SBP) 1

Site-specific cultures should be performed based on clinical suspicion 1

Imaging studies directed at suspected source:

• CT abdomen/pelvis for intra-abdominal pathology 1
• Additional chest imaging if respiratory symptoms present 1

Non-Infectious Considerations

Medication review for drugs causing neutrophilia:

• Lithium 1
• Beta-agonists 1
• Epinephrine 1
• Corticosteroids (from general medical knowledge)

Rule out laboratory artifact: Repeat CBC in citrate anticoagulant if EDTA-induced leukocyte aggregation is suspected (can cause falsely low counts on initial testing) 3

Management Algorithm

If hemodynamically stable: Complete diagnostic workup first before initiating antibiotics 2

If sepsis criteria present: Initiate broad-spectrum empiric antibiotics within 1 hour of recognition, with aggressive fluid resuscitation and vasopressor support if hypotension persists 2

Critical Pitfalls to Avoid

• Do not ignore elevated neutrophil count when total WBC is only mildly elevated - left shift can occur with normal WBC and still indicate serious bacterial infection 1, 2
• Do not rely on automated analyzer alone - manual differential is essential to assess band forms and immature neutrophils 2
• Do not treat asymptomatic, hemodynamically stable patients with antibiotics based solely on laboratory findings without clinical correlation 2
• Do not delay antibiotics in severe sepsis/septic shock while awaiting culture results 2
• Pay attention to the magnitude of abnormality - very high neutrophil percentages (approaching 90-100%) exponentially increase bacteremia probability and should prompt aggressive investigation 4