What are the causes and treatments of elevated neutrophils?

Causes of Elevated Neutrophils

Bacterial infections are the most common and clinically significant cause of neutrophilia, with specific laboratory thresholds providing strong diagnostic evidence for infection requiring immediate evaluation and treatment. 1

Primary Infectious Causes

Bacterial Infections

• Bacterial infections represent the most frequent cause of neutrophilia, with an absolute band neutrophil count ≥1,500 cells/mm³ carrying the highest likelihood ratio (14.5) for documented bacterial infection. 1
• A neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection, while a left shift (≥16% band neutrophils) has a likelihood ratio of 4.7, even when total WBC count remains normal. 1
• Common bacterial infections causing neutrophilia include:
  • Respiratory tract infections 1
  • Urinary tract infections 1
  • Skin and soft tissue infections 1
  • Gastrointestinal infections 1
  • Cholecystitis and cholangitis (particularly with right upper quadrant pain) 2
  • Spontaneous bacterial peritonitis in cirrhotic patients (ascitic fluid neutrophils >250/mm³) 1, 2

Specific High-Risk Organisms

• Staphylococcus aureus, gram-negative bacilli (particularly E. coli and Pseudomonas aeruginosa), and Candida albicans are the most common causative organisms in patients with recurrent infections and neutrophilia. 3
• Pseudomonas aeruginosa colonization is strongly associated with persistent neutrophil elevation and inflammatory responses. 4

Fungal and Viral Infections

• Fungal infections, particularly Aspergillus colonization and fungal pneumonia, can trigger significant neutrophil recruitment and activation. 4
• Cytomegalovirus infection engages both innate and adaptive immunity, causing upregulation of inflammatory markers and neutrophil mobilization. 4

Non-Infectious Causes

Medications

• Lithium, beta-agonists, and epinephrine are the primary medications that cause neutrophilia through direct bone marrow stimulation or altered neutrophil trafficking. 1

Inflammatory Conditions

• Neutrophils play a destructive role in chronic inflammatory diseases including rheumatoid arthritis, where they accumulate in synovial tissue and joint fluid, secreting proteases and toxic oxygen metabolites that damage cartilage and bone. 5
• Chronic obstructive pulmonary disease and adult respiratory distress syndrome involve neutrophil-mediated tissue damage. 3, 6
• Autoimmune, cardiovascular, and neurodegenerative diseases can feature neutrophil dysregulation with hyper-activation and extended survival contributing to pathogenesis. 6

Post-Infectious States

• Respiratory infections with Mycoplasma pneumoniae and Chlamydophila cause considerable neutrophil transmigration across bronchial epithelial cells, with sputum analysis showing increased neutrophils that can persist for weeks. 4

Critical Diagnostic Thresholds

When evaluating neutrophilia, specific laboratory values determine the urgency and likelihood of serious bacterial infection:

• Total WBC ≥14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 1
• WBC >20,000 cells/mm³ is associated with increased mortality in bloodstream infections and suggests severe sepsis 2
• The presence of elevated WBC or left shift warrants careful assessment for bacterial infection even without fever 1

Diagnostic Approach

Immediate Laboratory Assessment

• Obtain a complete blood count with manual differential (preferred over automated) to assess absolute neutrophil count, absolute band count, and presence of toxic granulation within 12-24 hours of symptom onset. 1, 7
• Manual differential is essential to accurately assess bands and other immature forms. 1

Clinical Evaluation

• Assess for fever (>38.2°C/101°F), chills, or rigors as markers of systemic infection. 7
• Examine for localized infection signs: respiratory symptoms (cough, dyspnea), urinary symptoms (dysuria, frequency), skin lesions, abdominal pain, or peritoneal signs. 1, 7
• Review medication history for drugs causing neutrophilia. 7

Targeted Diagnostic Testing

• Blood cultures should be obtained if systemic infection is suspected, along with C-reactive protein to assess inflammatory status. 1, 7
• Site-specific cultures based on symptoms: urine culture for urinary symptoms, sputum culture for respiratory symptoms. 1, 7
• Chest imaging if respiratory symptoms are present. 1
• In cirrhotic patients with ascites, perform diagnostic paracentesis immediately (neutrophil count >250/mm³ indicates spontaneous bacterial peritonitis requiring immediate antibiotics). 1, 2, 7
• Ultrasound first-line for suspected biliary disease; CT with IV contrast for suspected abdominal abscesses. 2

Treatment Principles

Infection Management

• If clinical signs of infection are present (fever, localized symptoms, or hemodynamic instability), initiate empiric broad-spectrum antibiotics immediately without waiting for culture results. 7
• For high-risk patients (hemodynamically unstable, immunocompromised, or suspected severe sepsis), use IV antipseudomonal beta-lactam (ceftazidime, cefepime, or piperacillin-tazobactam). 7
• For low-risk stable patients with suspected bacterial infection, oral ciprofloxacin plus amoxicillin-clavulanate is appropriate. 7
• Reassess clinical status and laboratory parameters at 48-72 hours, adjusting therapy based on culture results. 7

Post-Infectious Neutrophilia

• Antibiotics have no role in treating post-infectious cough and neutrophilia, as bacterial infection is not the cause. 4
• Consider inhaled ipratropium as first-line therapy for persistent post-infectious symptoms. 4
• For severe cases affecting quality of life, consider 30-40 mg prednisone daily for a short, finite period after ruling out other causes. 4

Common Pitfalls to Avoid

• Do not overlook absolute neutrophil count elevation when total WBC is only mildly elevated—left shift can occur with normal WBC and still indicate bacterial infection. 1, 7
• Do not delay antibiotic therapy in symptomatic patients while waiting for culture results. 7
• Do not treat asymptomatic patients with antibiotics based solely on mildly elevated neutrophil counts. 1, 7
• Do not ignore neutrophil percentage of 84% when total WBC is normal, as this can still indicate bacterial infection. 1
• In the absence of fever, leukocytosis, left shift, or specific clinical manifestations of focal infection, additional diagnostic tests may not be indicated. 1

Special Populations

Cancer Patients

• Chemotherapy-induced neutropenia increases infection risk, with risks greatest at neutrophil counts <100 cells/mcL. 4
• Elevated neutrophils with fever in cancer patients require immediate broad-spectrum antibiotics regardless of absolute neutrophil count. 7
• HIV-positive patients with cancer may be more susceptible to infectious complications and require prophylaxis based on CD4+ T-cell counts. 4

Immunocompromised Patients

• Patients with chronic lymphocytic leukemia or hairy cell leukemia have profound immunosuppression; any fever requires prompt antibiotic therapy. 7
• Neutrophil function disorders (chronic granulomatous disease, leukocyte adhesion deficiency) predispose to recurrent cutaneous, periodontal, respiratory, or soft tissue infections requiring aggressive treatment with surgical drainage and antibiotics. 3