What antibiotic should be given to an adult patient with leukocytosis (elevated White Blood Cell count) suggestive of a bacterial infection?

Antibiotic Selection for Elevated WBC Count

You cannot prescribe antibiotics based solely on an elevated white blood cell count without identifying the source and likely pathogens—leukocytosis alone does not indicate bacterial infection and empiric broad-spectrum antibiotics in this setting are associated with increased mortality, prolonged hospitalization, and resistant organism colonization.

Critical First Step: Determine If Infection Is Actually Present

• Leukocytosis has numerous non-infectious causes including physiological stress (38% of cases), medications (11%), hematological disease (6%), and tissue necrosis or inflammation (6%) 1
• In hospitalized patients with unexplained leukocytosis, most have extensive tissue damage rather than active infection driving the WBC elevation, often meeting criteria for persistent inflammation-immunosuppression and catabolism syndrome (PICS) 2
• Deep eosinopenia (with specificity of 94%) combined with elevated CRP >40 mg/L or fever >38.5°C provides high specificity for bacterial infection 3

When Infection Is Suspected: Source Identification Algorithm

Step 1: Obtain Cultures BEFORE Starting Antibiotics

• Blood cultures, urine cultures, and site-specific cultures should be obtained prior to antibiotic initiation 4
• Sputum (spontaneous or induced) should be collected when respiratory infection is suspected 4

Step 2: Identify the Most Likely Source

For respiratory symptoms (cough, dyspnea, infiltrate):

• Community-acquired pneumonia: Amoxicillin-clavulanate 1.75-4g/250mg daily OR ceftriaxone 2g IV daily 4
• Nosocomial pneumonia: Piperacillin-tazobactam 4.5g IV three times daily OR ceftazidime 2g IV three times daily; add vancomycin 30-60 mg/kg/day IV if MRSA risk factors present 4, 5

For urinary symptoms (dysuria, frequency, flank pain):

• Uncomplicated UTI: Amoxicillin-clavulanate 625mg three times daily for 14 days 4
• Complicated UTI/pyelonephritis: Ciprofloxacin 500-750mg twice daily OR ceftriaxone 2g IV daily 4

For abdominal symptoms (pain, peritoneal signs):

• Mild-moderate intra-abdominal infection: Amoxicillin-clavulanate OR ciprofloxacin + metronidazole 4
• Severe intra-abdominal infection: Ceftriaxone + metronidazole OR piperacillin-tazobactam 4

For skin/soft tissue (erythema, warmth, purulence):

• Non-purulent cellulitis: Benzylpenicillin OR cefazolin 4
• Purulent/MRSA suspected: Vancomycin 30-60 mg/kg/day IV OR linezolid 600mg twice daily 4, 5

For sinusitis symptoms (facial pain, nasal discharge):

• Acute bacterial sinusitis: Amoxicillin-clavulanate 1.75-4g/250mg daily for 10-14 days 4
• Treatment failure after 72 hours: Switch to levofloxacin 750mg daily 4, 6

Common Pitfalls to Avoid

Pitfall #1: Empiric Broad-Spectrum Antibiotics Without Source Control

• In a study of 17,430 sepsis patients, unnecessarily broad empiric antibiotics (targeting MRSA, VRE, or resistant gram-negatives when not present) were associated with increased mortality (OR 1.22,95% CI 1.06-1.40) 7
• Resistant organisms were uncommon: MRSA 11.7%, ceftriaxone-resistant gram-negatives 13.1%, VRE 2.1%, ESBLs 0.8% 7

Pitfall #2: Continuing Antibiotics for Persistent Leukocytosis Alone

• Patients with unexplained leukocytosis received prolonged broad-spectrum antibiotics without benefit, leading to Clostridioides difficile infection in 21% of cases 2
• If fever resolves but leukocytosis persists after treating intra-abdominal sepsis, 33% develop recurrent infection requiring surgical intervention—not more antibiotics 8

Pitfall #3: Missing Clostridioides difficile as the Cause

• C. difficile infection causes 16% of leukocytosis cases overall and 25% of cases with WBC >30,000/mm³ in non-hematologic patients 1
• Consider C. difficile testing even without diarrhea when WBC ≥15,000/mm³ 1

Special Considerations

For patients with MRSA history requiring coverage:

• Vancomycin 30-60 mg/kg/day IV divided in 2-4 doses (loading dose 25-30 mg/kg for seriously ill) 9, 5
• Alternative: Linezolid 600mg twice daily (contraindicated with serotonin reuptake inhibitors) 9, 5
• Add gram-negative coverage with cefepime or piperacillin-tazobactam until cultures available 9

For neutropenic patients (granulocytes <100/mm³):

• Combination therapy with anti-pseudomonal beta-lactam plus aminoglycoside provides synergy 4
• Continue broad-spectrum antibiotics even if fever persists, as discontinuation is associated with fatal bacteremia 4

Treatment duration:

• Standard duration for most infections: 7-14 days 9
• Adjust therapy based on culture results and clinical response 6